Naturally Occurring Cinnamic Acid Sugar Ester Derivatives.

Cinnamic acid sugar ester derivatives (CASEDs) are a class of natural product with one or several phenylacrylic moieties linked with the non-anomeric carbon of a glycosyl skeleton part through ester bonds. Their notable anti-depressant and brains protective activities have made them a topic of great interest over the past several decades. In particular the compound 3',6-disinapoylsucrose, the index component of Yuanzhi (a well-known Traditional Chinese Medicine or TCM), presents antidepressant effects at a molecular level, and has become a hotspot of research on new lead drug compounds. Several other similar cinnamic acid sugar ester derivatives are reported in traditional medicine as compounds to calm the nerves and display anti-depression and neuroprotective activity. Interestingly, more than one third of CASEDs are distributed in the family Polygalaceae. This overview discusses the isolation of cinnamic acid sugar ester derivatives from plants, together with a systematic discussion of their distribution, chemical structures and properties and pharmacological activities, with the hope of providing references for natural product researchers and draw attention to these interesting compounds.

1. Introduction

As a class of natural products, cinnamic acid sugar ester derivatives (CASEDs) have become a research focus owing to their structural diversity, together with distinctive and remarkable pharmacodynamic actions, such as anti-depression, anti-cancer, anti-oxidant, anti-inflammatory and anti-viral activities [1,2,3,4,5]. They have one or more phenylacrylic (Ph-CH=CH-CO-) moieties or their derivatives linked to the non-anomeric carbon skeletons of the glycosyl part through ester linkage-bonds. The phenylacrylic group, also named cinnamic acid part, may usually contain hydroxyl or methoxy substituted groups (Figure 1). The aglycone group is the core structure, and includes monosaccharides, disaccharides, trisaccharides, tetrasaccharides, pentasaccharides, hexsaccharides and heptasaccharides. There are one or several -OH groups on the non-anomeric carbon skeleton, connected with the cinnamic acid moiety.

Figure 1

Substituent groups.

Since 1968 [6], more than 330 CASEDs have been found in the medicinal plants of the families Polygalaceae, Scrophulariaceae, Liliaceae, Oleaceae, Bignoniaceae, Polygonaceae, Orobanchaceae, Rosaceae, Lamiaceae, Labiatae, Gesneriaceae, Rubiaceae, Cruciferae, Plantaginaceae, Verbenaceae, Magnoliaceae, Amaranthaceae, Smilacaeae, Sterculiaceae, Hymenophyllaceae and Asclepiadaceae (Table 1). Interestingly, more than one third of CASEDs are distributed in the family Polygalaceae, which is used for tranquilizing the mind and promoting intelligence as in Traditional Chinese Medicine (TCM) [1]. Yuanzhi, the dried root of Polygala tenuifolia, a representative plant from the Polygalaceae, is a well-known TCM used for its sedative, psychotic, cognitive and depressant effects. It is used in the clinic for tranquilizing and reinforcing the mind, and is commonly applied to physical and mental illness.

Table 1

The Family Distribution of CASEDs.

Family	Number	Family	Number
Asclepiadaceae	1	Gesneriaceae	8
Hymenophyllaceae	1	Labiatae	11
Sterculiaceae	1	Lamiaceae	11
Amaranthaceae	2	Rosaceae	13
Smilacaeae	3	Orobanchaceae	16
Magnoliaceae	3	Polygonaceae	19
Rubiaceae	5	Oleaceae	20
Plantaginaceae	6	Bignoniaceae	22
Cruciferae	6	Liliaceae	34
Verbenaceae	7	Scrophulariaccae	58
Polygalaceae	126

The oligosaccharide cinnamic acid esters are regarded as the predominant active antidepressant ingredients. 3′,6-Disinapoylsucrose (DISS, 73), as the index component of Yuanzhi, has been studied to the level of the molecular mechanism of its antidepressant effects, representing a hotspot of research on new drug precursor compounds [7]. There are also other multiple reports [8,9] on the antidepressant effects of sibiricose A5 (28) and tenuifoliside A (51). There are additionally several active compounds from Scrophulariae Radix, Rehmannia Radix, Smilacis China Rhizoma, which according to common wisdom, calm the nerves with anti-depression and neuroprotective activity (Table 2).

Table 2

The Principal Compounds of CASEDs Distributed in TCMs.

Name in TCM	Sources	Traditional Effect	Medicinal Parts	Compounds	Activity	Refs.
Polygalae Radix	Polygala tenuifolia Willd.	Common wisdom calms the nerves, restoring normal coordination between heart and kidney, Expectoration, subsidence of a swelling	Root	51, 52, 72, 73, 280–290, 292, 321–324	Anti-depression activity, neuroprotective activity	[10,11,12]
	Polygala sibirica L.			28–30, 50, 51, 73, 75, 78, 88	Anti-depression activity, neuroprotective activity, antioxidant activity	[13]
Smilacis China Rhizoma	Smilaz china L.	Syphilis, gout, and rheumatism	Root	39, 40, 45, 47, 79, 98, 99, 101, 107	Anticancer activity	[14]
	Smilax bracteata C. Presl			38, 41, 42, 45–47, 105, 106	Antioxidant activity	[15]
Scrophula-riae Radix	Scrophularia ningpoensis Hemsl.	Clearing heat and cooling blood, nourishing yin to reduce pathogenic fire, detoxicating and resolving a mass	Root	14, 53, 59, 132	Antioxidative activity	[16,17]
Scrophula-riae Radix	Scrophularia buergeriana Miq.	Clearing heat and cooling blood, nourishing yin to reduce pathogenic fire, detoxicating and resolving a mass	Root	11, 12, 13, 15	Neuroprotective	[18]
Rehmann-ia Radix	Rehmannia glutinosa var. Purpurea	Clearing heat and cooling blood, promoting the secretion of saliva or body fluid	Root	124, 125, 131, 133, 136, 138, 207–212	PKC inhibitory activity, antiinflammatory effects, antiviral activity, antibacterial activity	[19]

Up to now, there is no relevant literature that analyzes all those CASED compounds systematically. Therefore, this paper is aimed at systematically clarifying the distribution, chemical structures and pharmacological activities of CASEDs, in the hope of drawing more researchers’ attention to these interesting substances.

2. Chemical Constituents

Cinnamic acid sugar ester derivatives (CASEDs) are an important type of natural product. Structurally, they have a glycosyl linked with the phenylacrylic group using ester bonds. The glycosyl part maybe contain one, or several sugar units, which are attached via an -OH group to another -OH by condensation reactions. So far, glucopyrannosyl, rhamnopyranosyl, fructofuranosyl, arabinopyranosyl, galactopyranosyl, apiofuranosyl, xylopyranosyl, lyxopyranosyl, allopyranosyl, fucopyranosyl and lactopyranosyl moieties have been reported to occur in CASEDs. The glycosyl portion usually has an anomeric carbon of one sugar connected to the C-2, C-3 and C-4 of the other glycosyl group. Here, the non-anomeric carbon of the glycosyl part connected (Table 3).

Table 3

Cinnamic Acid Sugar Ester Derivatives.

No.	Name	Source	Refs.
1	6-O-Caffeoyl-1-O-p-coumaroyl-β-d-glucopyranose	Prunus buergeriana	[20]
2	1,6-Di-O-caffeoyl-β-d-glucopyranose	Prunus buergeriana; Coussarea hydrangeifolia	[20,21]
3	Osmanthuside E	Osmanthus asiaticus	[22]
4	1,6-Diferuloyl glucose	Sterculia foetida	[23]
5	Eutigoside A	Ligustrum purpurascens	[24]
6	Osmanthuside A	Ligustrum purpurascens	[24]
7	2-(3,4-Dihydroxyphenyl)-ethyl-(6-O-caffeoyl)-β-d-glucopyranoside or calceolarioside B	Calceolaria hypericina; Prunus ssiori; Paraboea glutinosa	[25,26]
8	3,4-Dihydroxyphenethyl alcohol 4-O-Caffeoyl-β-d-allopyranoside or calceolarioside A or derhamnosylverbascoside	Trichomanes reniforme Forst.f; Calceolaria hypericina; Lantana camaro L.	[25,27,28]
9	1′-O-β-d-(1-Hydroxy-4-oxo-2,5-cyclohexadien)-ethyl-6′-O-caffeoylglucopyranoside or calceolarioside D	Calceolaria hypericina	[25]
10	2-(3,4-Methylenedioxyphenyl)-ethyl-(6-O-caffeoyl)-β-d-glucopyranoside	Prunus ssiori	[29]
11	4-O-(E)-p-Methoxycinnamoyl-α-l-rhamno-pyranoside or buergeriside C3	Scrophularia buergeriana	[18]
12	2-O-Acetyl-3-O-(E)-p-methoxycinnamoyl-α-l-rhamnopyranoside or buergeriside B1	Scrophularia buergeriana	[18]
13	2-O-Acetyl-3,4-di-O-(E)-p-methoxycinnamoyl-α-l-rhamnopyranoside or buergeriside A1	Scrophularia buergeriana	[18]
14	3-O-Acetyl-2-O-p-methoxycinnamoyl-α(β)-l-rhamnopyranose or ningposide D	Scrophularia ningpoensis	[16]
15	2-O-Acetyl-3-O-(Z)-p-methoxycinnamoyl-α-l-rhamnopyranoside or buergeriside B2	Scrophularia buergeriana	[18]
16	6-O-p-Coumaroyl-d-glucopyranose	Prunus buergeriana	[20]
17	6-O-Caffeoyl-d-glucopyranose or 6-O-Caffeoyl-d-glucopyranoside	Prunus buergeriana; Prunus ssiori	[20,29]
18	6-O-[E]-Sinapoyl-(α- and β-)-d-glucopyranoside	Cynanchum hancockianum	[30]
19	O-Acylglycoses	Ligustrum purpurascens	[24]
20	3,6-di-O-Caffeoyl-(α/β)-glucose	Rubus sanctus	[31]
21	6-O-Feruloyl-β-d-glucopyranosyl-(1→6)-glucitol or globularitol	Globularia orientalis	[32]
22	(2R)-[(6-O-Caffeoyl)-β-d-glucopyranosyloxy]-benzeneacetonitrile or grayanin	Prunus buergeriana	[20]
23	Scrophyloside A	Neopicrorhiza scrophulariiflora	[33]
24	Scrophyloside B	Neopicrorhiza scrophulariiflora	[33]
25	Hexane-1,2,3,4,5-pentanol 1-O-β-(6-O-(E)-feruloyl) glucopyranoside or paederol A	Paederia scandens	[34]
26	Butane-1,2,3,4-tetraol 1-O-β-(6-O-(E)-feruloyl) glucopyranoside or paederol B	Paederia scandens	[34]
27	Kaempferol 3-O-β-d-(6-O-p-E-Coumaroyl)-glucopyranoside	Froelichia floridana	[35]
28	3-O-Feruloylsucrose or sibiricose A5	Trillium kamtschaticum; Polygala sibirica	[13,36]
29	3′-Sinapoyl sucrose or sibiricose A6	Polygala sibirica; Polygala tricornis	[13,37]
30	3-O-[(E)-3,4,5-Trimethoxycinnamoyl]-β-d-fructo-furanosyl-(2→1)-α-d-glucopyranoside or glomeratose A	Polygala sibirica; Polygala tricornis; Polygala glomerata	[13,37,38]
31	3,6-Di-p-coumaroyl sucrose or lapathosides D	Polygonum lapathifolium	[39]
32	Heronioside A	Trillium kamtschaticum; Smilax glabra	[36,40]
33	Parispolyside F	Paris polyphylla var. yunnanensis	[41]
34	β-d-(1-Sinapoyl-3-feruloyl)-α-d-glucopyranoside	Polygala chamaebuxus	[42]
35	β-d-(l-Acetyl-3-feruloyl)-fructofuranosyl-α-d-gluco-pyranoside	Polygala chamaebuxus	[42]
36	β-d-(1,3-Disinapoyl)-fructofuranosyl-d-gluco-pyranoside	Polygala chamaebuxus	[42]
37	β-d-(1,3,6-Tri-p-coumaryl)-fructofuranosyl-α-d-glucopyranoside or hydropiperoside	Polygonum hydropiperitum; Polygonurn hydropiper	[39,43]
38	(1,3-O-di-p-Coumaroyl-6-O-feruloyl)-β-d-fructo-furanosyl-(2→1)-α-d-glucopyranoside or smilaside G	Smilax bracteata	[15]
39	1-p-Coumaroyl-3,6-diferuloyl sucrose or smilaside C	Smilax china	[14]
40	1-p-Coumaroyl-3,6-diferuloyl-4-acetyl sucrose or smilaside D	Smilax china	[14]
41	(3-O-p-Coumaroyl-1,6-O-diferuloyl)-β-d-fructo-furanosyl-(2→1)-α-d-glucopyranoside or smilaside J	Smilax bracteata	[15]
42	1,3,6-O-Triferuloyl-β-d-fructofuranosyl-(2→1)-α-d-glucopyranoside or smilaside L	Smilax bracteata	[15]
43	3-O-[(E)-3,4,5-Trimethoxycinnamoyl]-β-d-fructo-furanosyl-(2→1)-(6-O-acetyl)-α-d-glucopyranoside or tricornose A	Polygala tricornis	[37]
44	Regaloside A	Trillium kamtschaticum	[36]
45	6′-Acetyl-3,6-diferuloylsucrose or helonioside B	Smilax china; Smilax bracteata; Polygonum perfoliatum; Heterosmilax erythrantha	[14,15,44,45]
46	(1,3-O-di-p-Coumaroyl-6-O-feruloyl)-β-d-fructo-furanosyl-(2→1)-(6-O-acetyl)-α-d-glucopyranoside or smilaside I	Smilax bracteata	[15]
47	1-p-Coumaroyl-3,6-diferuloyl-6′-acetyl sucrose or smilaside E	Smilax china; Smilax bracteata	[14,15]
48	Reiniose C	Polygala reinii Fr.et Sav	[46]
49	6-O-Benzoyl-3′-O-3,4,5-trimethoxycinnamoyl-sucrose or 3-O-[(E)-3,4,5-trimethoxy-cinnamoyl]-β-d-fructofuranosyl-(2→1)-(6-O-benzoyl)-α-d-glucopyranoside or [3-O-(3,4,5-trimethoxycinnamoyl]-β-d-fructo-furanosyl-(6-O-benzoyl)-α-d-glucopyranoside	Polygala tricornis; Polygala glomerata; Polygala reinii Fr.et Sav	[37,38,46]
50	3′-Sinapoyl-6-benzoyl sucrose or 6-O-benzoyl-3′-O-sinapoylsucrose 6-O-benzoyl-3′-O-sinapoylsucrose or (3-O-[(2E)-3-(4-hydroxy-3,5-dimethoxyphenyl)-1-oxoprop-2-enyl]-β-d-fructofuranosyl 6-O-benzoyl-α-d-glucopyranoside)	Polygala sibirica; Polygala tricornis; Polygala telephioidesWilld.	[13,37,47]
51	β-d-[3-O-(3,4,5-Trimethoxycinnamoyl)]-fructo-furanosyl-α-D-[6-O-(p-hydroxybenzoyl)]-gluco-pyranoside or tenuifoliside A	Polygala tenuifolia; Polygala sibirica	[10,11,12,13]
52	β-d-(3-O-Sinapoyl)-fructofuranosyl-α-d-(6-O-(p-hydroxybenzoyl)]-glucopyranoside or tenuifoliside B	Polygala tenuifolia	[10]
53	Sibirioside A	Scrophularia ningpoensis Hemsl	[17]
54	3-O-(E)-Sinapoyl-β-d-fructofuranosyl-(2→1)-[6-O-(E)-p-coumaroyl]-α-d-glucopyranoside or glomeratose B	Polygala glomerata	[38]
55	3-O-[(E)-3,4,5-Trimethoxycinnamoyl]-β-d-fructo-furanosyl-(2→1)-[6-O-(E)-p- coumaroyl] -α-d-glucopyranoside or glomeratose C	Polygala glomerata	[38]
56	3,4-O-β-d-Di-feruloyl-fructofuranosyl-6-O-α-d-(p-coumaroyl)-glucopyranoside	Monnina obtusifolia H.B.K.	[48]
57	6′-O-p-Coumarylhydropiperoside or vanicoside D	Polygonum pensylvanicum	[49]
58	1,3,6′-Tri-p-coumaroyl-6-feruloyl sucrose or diboside A	Fagopyrum dibotrys (D. Don.) Hara.	[50]
59	6-O-Caffeoyl-β-d-fructofuranosyl-(2→1)-α-d-gluco-pyranoside	Scrophularia ningpoensis Hemsl; Globularia orientalis	[17,32]
60	3,4-O-β-d-Di-feruloyl-fructofuranosyl-6-O-α-d-(caffeoyl)-glucopyranoside	Monnina obtusifolia H.B.K.	[48]
61	Reiniose A	Polygala reinii Fr.et Sav	[46]
62	6-O-Feruloyl-β-d-fructofuranosyl-(2→1)-α-d-glucopyranoside or β-d-fructofuranosyl-6-O-feruloyl-α-d-glucopyranoside or arillatose B	Globularia orientalis; Polygala arillata	[32,51]
63	1,6′-Diferuloyl-3,6-di-p-coumaroylsucrose or lapathoside A	Polygonum lapathifolium	[39]
64	1,6,6′-Triferuloyl-3-p-coumaroyl sucrose or lapathoside B	Polygonum lapathifolium	[39]
65	6′-Feruloyl-3,6-di-p-coumaroyl sucrose or lapathoside C	Polygonum lapathifolium	[39]
66	6′-Feruloyl-1,6-di-p-coumaroyl sucrose or hydropiperoside A	Polygonum hydropiper L.	[52]
67	Vanicoside B	Polygonum perfoliatum; Polygonum pensylvanirum	[44,53]
68	4-Acetyl-3,6′-diferuloylsucrose	Lilium speciosum var. rubrum; Lilium longiflorum	[54,55]
69	6-Acetyl-3,6′-diferuloylsucrose	Lilium speciosum var. rubrum	[54]
70	4,6-Diacetyl-3,6′-diferuloylsucrose	Lilium speciosum var. rubrum	[54]
71	3,6′-Diferuloylsucrose	Lilium speciosum var. rubrum;Lilium longiflorum	[54,55]
72	β-d-[3-O-(3,4,5-Trimethoxycinnamoyl)]-fructo-furanosyl-α-d-(6-O-sinapoyl)-glucopyranoside or tenuifoliside C	Polygala tenuifolia; Polygala tricornis; Polygala glomerata; Polygala reinii Fr.et Sav; Polygala japonica Houtt.	[10,37,38,46,56]
73	3′,6-Disinapoyl sucrose or 3-O-(E)-sinapoyl-β-d-fructofuranosyl-(2→1)-[6-O-(E)-sinapoyl]-α-d-glucopyranoside	Polygala tenuifolia; Polygala sibirica; Polygala tricornis; Polygala glomerata; Polygala reinii Fr.et Sav; Securidaca longipedunculata; Polygala virgata	[10,13,37,38,46,57,58]
74	β-D-(3,4-Disinapoyl)fructofuranosyl-α-d-(6-sinapoyl)glucopyranoside	Securidaca longipedunculata	[57]
75	6-O-Sinapoylsucrose or sibiricose A1	Polygala sibirica	[13]
76	3-O-Feruloyl-β-d-fructofuranosyl-(6-O-sinapoyl)-α-d-glucopyranoside	Polygala reinii Fr.et Sav	[46]
77	3-O-[(E)-3,4,5-Trimethoxycinnamoyl]-β-d-fructo-furanosyl-(2→1)-[6-O-(E)-p-coumaroyl]-α-d-glucopyranoside or glomeratose D	Polygala glomerata	[38]
78	6-O-3,4,5-Trimethoxycinnamoyl sucrose or sibiricose A2	Polygala sibirica	[13]
79	3,6-Diferuloyl-4′,6′-diacetylsucrose or smilaside A	Smilax china	[14]
80	3-O-[(E)-3,4,5-Trimethoxycinnamoyl]-β-d-fructo-furanosyl-(2→1)-(4-O-acetyl)-(6-O-benzoyl)-α-d-glucopyranoside or tricornoses B	Polygala tricornis	[37]
81	4′-Acetyl-3,6′-diferuloylsucrose	Lilium speciosum var. rubrum	[54]
82	β-d-(3-O-Sinapoyl)fructofuranosyl-α-d-(4-O-acetyl-6-O-sinapoyl)glucopyranoside	Polygala virgata	[58]
83	Reiniose B	Polygala reinii Fr.et Sav	[46]
84	4-O-Benzoyl-3′-3,4,5-trimethoxycinnamoylsucrose or [3-O-(3,4,5-trimethoxycinnamoyl)]-β-d-fructofuranosyl-(4-O-benzoyl)-α-d-gluco-pyranoside	Polygala tricornis; Polygala reinii Fr.et Sav	[37,46]
85	(3,6-O-Diferuloyl)-β-d-fructofuranosyl-(2→1)-(4-O-p-coumaroyl-6-O-acetyl)-α-d-glucopyranoside or quiquesetinerviuside D	Calamus quiquesetinervius Burret	[4]
86	(3,6-O-Diferuloyl)-β-d-fructofuranosyl-(2→1)-(4-O-feruloyl)-α-d-glucopyranoside or quiquesetinerviuside A	Calamus quiquesetinervius Burret	[4]
87	(3,6-O-Diferuloyl)-β-d-fructofuranosyl-(2→1)-(4-O-feruloyl-6-O-acetyl)-α-d-glucopyranoside or quiquesetinerviuside B	Calamus quiquesetinervius Burret	[4]
88	3′,4-O-Disinapoylsucrose or sibiricose A4	Polygala sibirica	[13]
89	1-O-Acetyl-3-O-p-coumaroyl-β-d-fructofuranosyl-3,6-di-O-acetyl-α-d-glucopyranoside	Prunus padus	[58]
90	(3,6-Di-O-feruloyl)-β-d-fructofuranosyl-(3,6-di-O-acetyl)-α-d-glucopyranoside	Smilax glabra	[40]
91	3′-O-Acetylvanicoside B or vanicoside F	Polygonum pensylvanicum	[49]
92	6,3′-Diacetyl-3,6′-diferuloylsucrose	Lilium speciosum var. rubrum	[54]
93	4,6,3′-Triacetyl-3,6′-diferuloylsucrose	Lilium speciosum var. rubrum	[54]
94	β-d-(3-O-Sinapoyl)fructofuranosyl-α-d-(3-O-acetyl-6-O-sinapoyl)glucopyranoside	Polygala virgata	[59]
95	Heterosmilaside	Heterosmilax erythrantha	[45]
96	1-O-Acetyl-3-O-p-coumaroyl-β-d-fructofuranosyl-3,4,6-tri-O-acetyl-α-d-glucopyranoside	Prunus padus	[58]
97	1,2′,6′-Triacetyl-3,6-diferuloylsucrose	Polygonum perfoliatum	[44]
98	2′,6′-Diacetyl-3,6-diferuloylsucrose	Polygonum perfoliatum; Smilax china; Heterosmilax erythrantha	[14,44,45]
99	1,3-Di-p-coumaroyl-6-feruloyl-2′,6′-diacetylsucrose or smilaside F	Smilax china	[14]
100	Smiglaside B	Smilax glabra	[40]
101	Smiglaside E	Smilax china; Smilax glabra	[14,40]
102	Vanicoside A	Polygonum perfoliatum; Polygonum pensylvanirum	[44,53]
103	2′-Acetyl-1,6′-diferuloyl-3,6-di-p-coumaroyl sucrose or hydropiperoside B	Polygonum hydropiper L.	[52]
104	2′-O-Acetylhydropiperoside or vanicoside C	Polygonum pensylvanirum	[49]
105	1-O-p-Coumaroyl-3,6-O-diferuloyl-β-d-fructo-furanosyl-(2→1)-(2-O-acetyl)-α-d-glucopyranoside or smilaside K	Smilax bracteata	[15]
106	(1,3-O-Di-p-coumaroyl-6-O-feruloyl)-β-d-fructo-furanosyl-(2→1)-(2-O-acetyl)-α-d-glucopyranoside or smilaside H	Smilax bracteata	[15]
107	3,6-Diferuloyl-2′-acetyl sucrose or smilaside B	Smilax china	[14]
108	2′,4′,6′-Triacetyl-3,6-diferuloylsucrose or smiglaside C	Smilax glabra; Polygonum perfoliatum	[40,44]
109	β-d-(1-O-Acetyl-3,6-O-trans-dicinnamoyl)fructo-furanosyl-α-d-(2,4,6-O-triacetyl)glucopyranoside or niruriside	Phyllanthus niruri L.	[60]
110	1,2′,4′,6′-Tetraacetyl-3,6-diferuloylsucrose	Polygonum perfoliatum	[44]
111	Smiglaside A	Smilax glabra	[40]
112	Smiglaside D	Smilax glabra	[40]
113	4′-O-Acetylvanicoside A or vanicoside E	Polygonum pensylvanicum	[49]
114	(3,6-O-Diferuloyl)-β-d-fructofuranosyl-(2→1)-(4-O-p-coumaroyl-2-O-acetyl)-α-d-glucopyranoside or quiquesetinerviuside E	Calamus quiquesetinervius Burret	[4]
115	(3,6-O-Diferuloyl)-β-d-fructofuranosyl-(2→1)-(4-O-feruloyl-2-O-acetyl)-α-d-glucopyranoside or quiquesetinerviuside C	Calamus quiquesetinervius Burret	[4]
116	3-O-p-Coumaroyl-β-d-fructofuranosyl2,3,4,6-tetra-O-acetyl-α-d-glucopyranoside	Prunus padus	[58]
117	1-O-Acetyl-3-O-p-coumaroyl-β-d-fructofuranosyl 2,3,6-tri-O-acetyl-α-d-glucopyranoside	Prunus padus	[58]
118	β-d-(1-O-Acetyl-3,6-O-p-E-dicoumaroyl)-fructo-furanosyl-α-d-(4′-O-acetyl-2′-O-p-E-coumaroyl)-glucopyranoside	Froelichia floridana	[35]
119	2-Feruloyl-O-α-d-glucopyranoyl-(1′→2)-3,6-O-feruloyl-β-d-fructofuranoside	Paris polyphylla var. yunnanensis	[61]
120	3-O-Caffeoyl-β-d-fructofuranosyl 2,3,4,6-tetra-O-acetyl-α-d-glucopyranoside	Prunus ssiori	[24]
121	Magnoloside A	Magnolia obovata Thunb	[62]
122	β-(p-Hydroxyphenyl)ethyl O-α-l-rhamno-pyranosyl-(1→3)-6-O-trans-p-coumaroyl-β-d-gluco-pyranoside or osmanthuside B6	Osmanthus asiaticus; Ligustrum purpurascens	[22,24]
123	β-(p-Hydroxyphenyl)ethyl O-α-l-rhamno-pyranosyl-(1→3)-4-O-cis-p-coumaroyl-β-d-gluco-pyranoside or osmanthuside D	Osmanthus asiaticus	[22]
124	Jionoside D	Rehmannia glutinosa var. Purpurea; Scrophularia nodosa L.	[19,63]
125	2-Phenylethyl O-α-l-rhamnopyranosyl-(1→3)-4-O-caffeoyl-β-d-glucopyranoside or jionoside C	Rehmannia glutinosa var. Purpurea	[19]
126	Osmanthuside B	Ligustrum purpurascens; cistanche salsa	[24,64]
127	Lipedoside A-II	Ligustrum purpurascens	[24]
128	Isoverbascoside	Lantana camaro L.; Pedicularis artselaeri; Pedicularis striata; Markhamia stipulate; Fernandoa adenophylla; Markhamia lutea; Scrophularia scorodonia	[15,29,65,66,67,68,69]
129		Scrophularia nodosa L.	[63]
130	6′-O-(E)-Cinnamoyl verbascoside	Osmanthus austrocaledonica	[65]
131	Acteoside or verbascoside	Rehmannia glutinosa var. Purpurea; Ligustrum purpurascens; Calceolaria hypericina; Lantana camaro L.; Scrophularia nodosa L.; Pedicularis artselaeri; Pedicularis striata; Markhamia stipulate; Fernandoa adenophylla; Markhamia lutea; Scrophularia scorodonia; Penstemon serrulatus Menz; Aeginetia indica Linn; Pedicularis lasiophrys; Lagotis stolonifera; Conandron ramoidioides; Paulownia tomentosa stem; Phlomis grandiflora; Pedicularis spicata; Pedicularis bngijora; cistanche salsa; Brandisia hancei; Phlomis linearis	[15,19,24,25,29,63,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84]
132	cis-Acteoside or cisacteoside	Scrophularia ningpoensis Hemsl; Scrophularia nodosa L.; Penstemon serrulatus Menz	[17,63,71]
133	Cistanoside C or leucosceptoside A or trans-leucosceptoside A	Rehmannia glutinosa var. Purpurea; Fernandoa adenophylla; Penstemon serrulatus Menz; Pedicularis bngijora; cistanche salsa; Lamiophlomis rotata	[19,69,71,79,85,86]
134	cis-Leucosceptoside A	Penstemon serrulatus Menz	[71]
135	2′′,3′′′-Diacetyl acteoside	Aeginetia indica Linn	[72]
136	2′-Acetyl acteoside	Rehmannia glutinosa var. Purpurea; cistanche salsa; Aeginetia indica Linn; Brandisia hancei	[19,64,72,82]
137	l′-O-β-d-(3-Methoxy-4-hydroxy-β-phenyl)-ethyl-6′-O-feruloyl-α-l-(2-acetyl)-rhamnosyl-(1→3′)-4′-acetylglucopyranoside or pedicularioside E	Pedicularis lasiophrys	[73]
138	Martynoside or trans-martynoside	Rehmannia glutinosa var. Purpurea; Pedicularis artselaeri; Fernandoa adenophylla; Penstemon serrulatus Menz; Paulownia tomentosa stem; Galeopws pubescens	[19,66,69,71,76,87]
139	cis-Martynoside	Penstemon serrulatus Menz	[71]
140	2-(4-Hydroxy-3-methoxyphenyl)ethyl O-α-l-rhamnopyranosyl-(1→3)-O-(4-O-feruloyl)-β-d-glucopyranoside or cistanoside D	cistanche salsa; Pedicularis artselaeri; Pedicularis lasiophrys; Pedicularis bngijora	[64,66,73,79]
141	2-(3′,4′-Dihydroxyphenyl)-ethanol 1-O-β-d-xylosyl-(1→3)-β-d-(4-caffeyl)-glucoside or conandroside	Conandron ramoidioides	[74]
142	Isonuomioside A	Paraboea glutinosa; Lantana camaro L.	[27,29]
143	Calceolarioside E	Paraboea glutinosa; Lantana camaro L.	[27,29]
144	Plantamajoside	Lagotis stolonifera	[75]
145	Isocistanoside F	Ligustrum purpurascens	[24]
146	α-l-Rhamnopyranosyl(1→3)-O-(4-O-caffeoyl)-d-glucopyranoseor cistanoside F	cistanche salsa	[85]
147	3-Hydroxy-4-methoxy-β-phenylethoxy-O-α-l-rhamnopyranosyl-(1→3)-6-O-feruloyl-β-d-gluco-pyranoside or isomartynoside	Galeopws pubescens	[87]
148	1′-O-β-d-(3,4-Dihydroxy-β-phenyl)-ethyl-4′-O-caffeoyl-β-d-xylopyranosyl-(1′′′→6′)-glucopyran oside or calceolarioside C	Calceolaria hypericina	[25]
149	4-Cinnamoyl desxylosyl mussatioside	Mussatia	[88]
150	1-O-trans-Caffeoyl-2′-O-trans-sinapoylgentiobiose.	Wasabia japonica Matsumura	[89]
151	1-O-trans-Feruloyl-2′-O-trans-sinapoylgentiobiose	Wasabia japonica Matsumura	[89]
152	1,2′-di-O-trans-sinapoylgentiobiose	Wasabia japonica Matsumura	[89]
153	1-(3′′,4′′-Dihydroxy-5′′-methoxy)-O-trans-cinnamoyl-2′-O-trans-feruloyl gentiobiose	Wasabia japonica Matsumura	[89]
154	1-(3′′,4′′-Dihydroxy-5′′-methoxy)-O-trans-cinnamoyl-2′-O-trans-sinapoylgentiobiose	Wasabia japonica Matsumura	[89]
155	1,2′-Di-(3′′,4′′-dihydroxy-5′′-methoxy)-O-trans-cinnamoyl gentiobiose	Wasabia japonica Matsumura	[89]
156	(5-O-E-Caffeoyl)-β-d-apio-d-furanosyl-(1→6)-β-d-glucopyranosyl benzoic acid ester or psydroside	Psydrax livida	[90]
157	Crenatoside	Orobanche crenata	[91]
158	Campneoside II or orobanchoside	Paulownia tomentosa stem; Orobanche crenata	[76,91]
159	Campneoside I	Paulownia tomentosa stem	[76]
160	Ligurobustoside C	Ligustrum purpurascens	[24]
161	Ligurobustoside I	Ligustrum purpurascens	[24]
162	1-O-{6-O-[3-O-(E,E)-(β,β′-bis-Sinapoyl)-β-d-fructo-furanosyl]}-α-d-glucopyranoside intramolecular ester or glomeratose E	Polygala glomerata	[38]
163	3-O-[(E)-Sinapoyl]-β-d-fructofuranosyl-(2→1)-[β-d-glucopyranosyl-(1→2)]-[6-O-(E)-sinapoyl]-α-d-glucopyranosideor tricornose D	Polygala tricornis	[37]
164	3-O-[(E)-3,4,5-Trimethoxycinnamoyl]-β-d-fructo-furanosyl-(2→1)-[β-d-glucopyranosyl-(1→2)]-[6-O-(E)-sinapoyl]-α-d-glucopyranoside or tricornose C	Polygala tricornis	[37]
165	3-O-(E)-3,4,5-Trimethoxycinnamoyl-[4-O-(E)-feruloyl]-β-d-fructofuranosyl-(2→1)-[β-d-gluco-pyranosyl-(1→2)]-[6-O-(E)-sinapoyl]-α-d- gluco-pyranoside or tricornose F	Polygala tricornis	[37]
166	3-O-(E)-3,4,5-Trimethoxycinnamoyl-[4-O-(E)-sinapoyl]-β-d-fructofuranosyl-(2→1)-[β-d-glucopyranosyl-(1→2)]-[6-O-(E)-sinapoyl]-α-d-glucopyranoside or tricornose E	Polygala tricornis	[37]
167	Reiniose E	Polygala reinii Fr.et Sav	[46]
168	Reiniose F	Polygala reinii Fr.et Sav	[46]
169	O-β-d-Glucopyranosyl-(1→3)-6-O-feruloyl -α-d-glucopyranosyl β-d-fructofuranoside or arillatose C	Polygala arillata	[51]
170	O-β-d-Glucopyranosyl-(1→3)-6-O-sinapoyl-α-d-glucopyranosyl β-d-fructofuranoside or arillatose D	Polygala arillata	[51]
171	O-β-d-Glucopyranosyl-(1→3)-α-d-gluco-pyranosyl-3′-O-feruloyl-β-d-fructofuranoside or arillatose E	Polygala arillata	[51]
172	O-β-d-Glucopyranosyl-(1→3)-α-d-gluco-pyr anosyl-3′-O-sinapoyl-β-d-fructofuranoside or arillatose F	Polygala arillata	[51]
173	3-Feruloyl-4-acetyl-6′-(13′-O-β-d-gluco-pyranosyl)feruloylsucrose	Lilium longiflorum	[55]
174	Reiniose D	Polygala reinii Fr.et Sav; Polyyala fallax	[46,92]
175	Dalmaisiose A	Polygala dalmaisiana	[93]
176	3,4-Dihydroxyphenylethanol-6-O-trans-caffeoyl-β-d-apiofuranosyl(1→5)-β-d-apiofuranosyl(1→3)-β-d-glucopyranoside or paraboside B	Paraboea glutinosa	[27]
177	3,4-Dihydroxyphenylethanol-4-O-trans-caffeoyl-β-d-apiofuranosyl(1→5)-β-d-apiofuranosyl(1→3)-β-d-glucopyranosideor paraboside A	Paraboea glutinosa	[27]
178	2-(3,4-Dihydroxyphenyl)ethyl 3,6-O-bis(β-d-apiofranosyl)-4-O-caffeoyl-β-d-glucopyranoside or paucifloside	Lysionotus pauciflorus	[94]
179	l′-O-β-d-(3,4-Dihydroxy-β-phenyl)-ethyl-4′-O-caffeoyl-β-d-apiosyl-(l→3′)-α-l-rhamnosyl-(l→6′)-glucopyranoside or pedicularioside A	Pedicularis striata; Markhamia lutea; Pedicularis striata pall ssp. arachnoidea; Pedicularis spicata	[5,67,77,78]
180	l′-O-β-d-(3,4-Dihydroxy-β-phenyl)-ethyl-4′-O-feruloyl-β-d-apiosyl(1→3′)-α-l-rhamnosyl-(1→6′)-glucopyranoside or pedicularioside M	Pedicularis striata pall ssp. arachnoidea	[77]
181	l′-O-β-d-(3-hydroxy-4-methoxy-β-phenyl)-ethyl-4′-feruloyl-β-d-apiosyl(l→3′)-α-l-rhamnosyl-(l→6′)-glucopyranoside or pedicularioside N	Pedicularis artselaeri; Pedicularis striata pall ssp. arachnoidea	[66,77]
182	l′-O-β-d-(3-Methoxy-4-hydroxy-β-phenyl)-ethyl-4′-O-feruloyl-β-d-apiosyl-(1→3′)-α-l-rhamnos yl-(1→6′)-glucopyranoside or pedicularioside H	Pedicularis spicata	[78]
183	3,4-Dihydroxy-β-phenylethoxy-O-[α-arabino-pyranosyl-(1′′′′→2′′)-α-rhamnopyranosyl-(1′′′→3′′)-6′′-O-caffeoyl-β-glucopyranoside] or markhamioside C	Markhamia stipulata	[68]
184	Ehrenoside	Veronica pectinata var. glandulosa; Aragoa cundinamarcensis	[75,95,96]
185	3,4-Dihydroxy-β-phenylethoxy-O-[α-arabino-pyranosyl-(1′′′′→2′′)-α-rhamnopyranosyl-(1′′′→3′′)-4-O-caffeoyl-6-O-acetyl-β-glucopyranoside or markhamioside D	Markhamia stipulata	[68]
186	2-(3,4-Dihydroxyphenyl)ethyl-O-α-l-arabino-pyranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→3)]-(4-O-trans-feruloyl)-β-d-glucopyranoside or verpectoside A	Veronica pectinata var. glandulosa	[95]
187	Lagotoside	Lagotis stolonifera	[75]
188	3,4-Dihydroxy-β-phenylethoxy-O-β-apiofuranosyl-(1→2)-α-rhamnopyranosyl-(1→3)-4-O-caffeoyl-β-glucopyranosideor 2′′-O-β-apiosylverbascoside	Markhamia stipulata ; Fernandoa adenophylla	[68,69]
189	1-O-(3,4-Dihydroxyphenyl)ethyl β-d-apiofuranosyl(1→2)-α-l-rhamnopyranosyl (1→3)-4-O-caffeoyl-6-acetyl-β-d-glucopyrano sideor luteoside A	Markhamia stipulate; Markhamia lutea	[5,68]
190	1-O-(3,4-Dihydroxyphenyl)ethyl β-d-apio-furanosyl(1→2)-α-l-rhamnopyranosyl(1→3)-6-O-caffeoyl-β-d-glucopyranosideor luteoside B	Markhamia stipulate; Markhamia lutea	[5,68]
191	1-O-(3,4-Dihydroxyphenyl)ethyl β-d-apio-furan osyl(1→2)-α-l-rhamnopyranosyl(1→3)-6-O-feruloyl-β-d-glucopyranoside or luteoside C	Markhamia lutea	[5]
192	3-Hydroxy-4-methoxy-β-phenylethoxy-O-[β-apio-furanosyl-(1′′′′→2′′)-α-rhamnopyranosyl-(1′′′→3′′)-6′′-O-feruloyl-β-glucopyranoside] or markhamioside B	Markhamia stipulate	[68]
193	3,4-Dihydroxy-β-phenylethoxy-O-[β-galacto-pyranosyl-(1′′′′→2′′)-α-rhamnopyranosyl-(1′′′→3′′)-4-O-caffeoyl-6-O-acetyl-β-glucopyranoside] or markhamioside E	Markhamia stipulate	[68]
194	2-(3,4-Dihydroxyphenyl)ethyl-O-β-d-gluco-pyranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→3)]-(4-O-trans-caffeoyl)-β-d-glucopyranoside or verpectoside B	Veronica pectinata var. glandulosa	[95]
195	2-(3,4-Dihydroxyphenyl)ethyl-O-β-d-gluco-pyranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→3)]-(4-O-trans-feruloyl)-β-d-glucopyranoside or verpectoside C	Veronica pectinata var. glandulosa	[95]
196	1′-O-β-d-(3-Methoxy-4-hydroxy-phenyl)-ethyl-α-l-rhamnosyl-(1→3′)-α-l-arabinosyl-(1→4′)-6′-O-feruloyl-glucopyranoside or pedicularioside I	Pedicularis bngijora	[79]
197	Angoroside A	Scrophularia nodosa L.; Scrophularia scorodonia	[63,70]
198	Scrophuloside B1	Scrophularia nodosa L.	[63]
199	Scrophuloside B2	Scrophularia nodosa L.	[63]
200	3,4-Dihydroxy-β-phenylethoxy-O-α-l-arabino-pyranosyl-(1→6)-α-l-rhamnopyranosyl-(1→3)-4-O-feruloyl-β-d-glucopyranoside or angoroside D	Scrophularia scorodonia	[70]
201	Angoroside C	Scrophularia nodosa L.	[63]
202	Forthysioside B	Markhamia lutea	[5]
203	6′-β-d-Apiofuranosyl cistanoside C	Lamiophlomis rotata	[86]
204	Lamiophlomiside A	Lamiophlomis rotata	[86]
205	cis-Lamiophlomiside A	Lamiophlomis rotata	[86]
206	Forsythoside B	Phlomis grandiflora; Phlomis fruticosa	[80]
207	Alyssonoside	Phlomis grandiflora; Phlomis fruticosa	[80]
208	2-(3,4-Dihydroxyphenyl)ethyl O-α-rhamno-pyranosyl-(1→3)-[β-d-galactopyranosyl-(l→6)]-(4-O-p-coumaroyl)-β-d-glucopyranoside or jionoside E	Rehmannia glutinosa var. Purpurea	[19]
209	Purpureaside C	Rehmannia glutinosa var. Purpurea; Scrophularia nodosa L.	[19,63]
210	Jionoside A1	Rehmannia glutinosa var. Purpurea	[19]
211	Jionoside A2	Rehmannia glutinosa var. Purpurea	[19]
212	Jionoside B1	Rehmannia glutinosa var. Purpurea	[19]
213	Jionoside B2	Rehmannia glutinosa var. Purpurea	[19]
214	Echinacoside	Ligustrum purpurascens; cistanche salsa	[24,81]
215	2-(4-Hydroxy-3-methoxyphenyl)ethyl O-α-l-rhamnopyranosyl-(1→3)-O-[β-d-glucopyrano syl(1→6)]-(4-O-caffeoyl)-β-d-glucopyranosideor cistanoside A	Ligustrum purpurascens	[81]
216	2-(4-Hydroxy-3-methoxyphenyl)ethyl O-α-l-rhamnopyranosyl-(1→3)-O-[β-d-glucopyran osyl(1→6)]-(4-O-feruloyl)-β-d-glucopyranoside or cistanoside B	Ligustrum purpurascens	[81]
217	Poliumoside	Brandisia hancei	[82]
218	[β-(3′,4′-Dihydroxylphenyl)-ethyl]-(2-O-acetyl)-(3,6-O-di-α-l-rhamnopyranosyl-(4-O-caffeoyl)β-d-glucopyranoside or brandioside	Brandisia hancei	[82]
219	Arenarioside	Scrophularia nodosa L.	[63]
220	1-O-3,4-(Sihydroxyphenyl)-ethyl-β-d-apiofuranosyl-(1→4)-α-l-rharmnopyranosyl-(1→3)-4-O-caffeoyl-β-d-glucopyranoside or myricoside	Markhamia lutea; Picria tel-ferae Lour.	[5,97]
221	Rossicaside B	Boschniakia rossica	[98]
222	Rossicaside A	Boschniakia rossica	[98]
223	2-O-Acetylrossicaside A	Ortbocarpus densiflourus var. gracilis	[99]
224	β-d-glucopyranosyl(1→4)-α-l-rhamnopyranosyl-(1→3)-(4-O-trans-caffeoyl)-d-glucopyranose	Boschniakia rossica	[98]
225	Lavandulifolioside	leonurus glaucescens	[83]
226	β-(3,4-Dihydroxyphenyl)-ethyl-O-α-L-arabinopyranosyl-(1→2)-α-L-rhamnopyranosyl-(l →3)-4-O-feruloyl-β-D-glucopyranoside or leonosides A	leonurus glaucescens	[83]
227	β-(3-Hydroxy,4-methoxyphenyl)-ethyl-O-α-l-arabinopyranosyl-(l→2)-α-l-rhamnopyranosyl-(1→3)-4-O-feruloyl-β-d-glucopyranoside or leonoside B	leonurus glaucescens	[83]
228	2R-Galactosyl-acteoside or lamalboside	Lamium album	[100]
229	3,4-Dihydroxy-β-phenylethoxy-O-β-d-gluco-pyranosyl-(1→2)-α-l-rhamnopyranosyl-(1→3)-4-O-caffeoyl-β-d-glucopyranoside or phlinoside A	Phlomis linearis	[84]
230	3,4-Dihydroxy-β-phenylethoxy-O-α-l-lyxo-pyranosyl-(1→2)-α-l-rhamnopyranosyl-(1→3)-4-O-caffeoyl-β-d-glucopyranoside or teucrioside	Teucrium chamaedrys	[101]
231	3,4-Dihydroxy-β-phenylethoxy-O-β-d-xylo-pyranosyl-(1→2)-α-L-rhamnopyranosyl-(1→3)-4-O-caffeoyl-β-d-glucopyranoside or phlinoside B	Phlomis linearis	[84]
232	3,4-Dihydroxy-β-phenylethoxy-O-β-d-xylo-pyranosyl-(1→2)-α-l-rhamnopyranosyl-(1→3)-4-O-feruloyl-β-d-glucopyranoside or phlinoside D	Phlomis lineuris	[102]
233	2-(4-Hydroxyphenyl)-ethyl-[3-O-α-l-rhamno-pyranosyl(1→4)-α-l-rhamnopyranosyl][6-O-p-coumaroyl]-O-β-d-glucopyranoside or ligupurpuroside C	Ligustrum purpurascens	[24]
234	2-(4-Hydroxyphenyl)-ethyl-[3-O-α-l-rhamno-pyranosyl(1→4)-α-l-rhamnopyranosyl][6-O-(E)-caffeoyl]-O-β-d-glucopyranoside or ligupurpuroside D	Ligustrum purpurascens	[24]
235	3-O-[α-l-Rhamnopyranosyl(1→4)-α-l-rhamno-pyranosyl]-4-O-(E)-caffeoyl-d-glucopyranose or ligupurpuroside F	Ligustrum purpurascens	[24]
236	Ligupurpuroside B	Ligustrum purpurascens	[24]
237	Ligurobustosides N	Ligustrum purpurascens	[24]
238	Ligupurpuroside A	Ligustrum purpurascens	[24]
239	3,4-Dihydroxy-β-phenylethoxy-O-α-l-rhamno-pyranosyl-(l→2)-α-l-rhamnopyranosyl-(1→3)-4-O-caffeoyl-β-d-glucopyranoside or phlinoside C	Phlomis linearis	[84]
240	3,4-Dihydroxy-β-phenylethoxy-O-α-l-rhamno-pyranosyl-(l→2)-α-l-rhamnopyranosyl-(l→3)-4-O-feruloyl-β-d-glucopyranoside or phlinoside E	Phlomis lineuris	[102]
241	Myricoside	Clerodendrum serratum	[103]
242	3-Hydroxy-4-methoxy-β-phenethyl-O-β-d-apio-furanosyl-(1→3)-α-l-rhamnopyranosyl-(1→3)-4-O-feruloyl-β-d-glucopyranoside or serratumoside A	Clerodendrum serratum	[103]
243	Aragoside	Aragoa cundinamarcensis	[96]
244	Persicoside	Aragoa cundinamarcensis	[96]
245	1′-O-β-d-(3-Hydroxy-4-methoxy-β-phenyl)-ethyl-4′-O-feruloyl-β-d-glucopyranosyl-(1→3)-α-l-rhamnosyl-(1→6′)-glucopyranoside or artselaeroside B	Pedicularis artselaeri	[66]
246	3,4-Dihydroxy-β-phenyl-ethyl-O-α-l-rhamno-pyranosyl-(1→2)-O-β-d-glucopyranosyl-(1→6)-3-O-caffeoyl-β-d-allopyranoside or magnoloside B	Magnolia obovata Thunb	[62]
247	α-l-Xylopyranosyl-(4′′→2′)-(3-O-β-d-gluco-pyranosyl)-1′-O-E-caffeoyl-β-d-glucopyranoside	Coussarea hydrangeifolia	[21]
248	2-(3,4-Dihydroxyphenyl)-R,S-2-ethoxyethyl-O-β-d-glucopyranosyl(1→4)-α-l-rhamno-pyranosyl(1→3)(4-O-trans-caffeoyl)-β-d-gluco-pyranoside or rossicaside F	Boschniakia rossica	[97]
249	4-Cinnamoyl desxylosylmussatioside	Mussatia	[88]
250	4-p-Coumaroylmussatioside	Mussatia	[88]
251	4-cis-p-Coumaroylmussatioside	Mursatia byacinthima	[104]
252	4-p-Methoxycmnamoylmussatioslde ormussatloside III	Mussatia	[88]
253	4-Feruloylmussatioside	Mussatia	[88]
254	4-Dimethylcaffeoylmussatloside or mussatioside II	Mussatia	[88]
255	3-O-[(E)-Sinapoyl]-β-d-fructofuranosyl-(2→1)-[β-d-glucopyranosyl-(1→4)-β-d-gluco-pyranosyl-(1→2)]-[6-O-(E)-sinapoyl]-α-d-gluco-pyranoside or tricornose G	Polygala tricornis	[37]
256	3-O-(E)-Sinapoyl-[4-O-(E)-p-coumaroyl]-β-d-fructofuranosyl-(2→1)-[β-d-glucopyranosyl-(1→4)-β-d-glucopyranosyl-(1→2)]-[6-O-(E)-sinapoyl]-α-d-glucopyranoside or tricornose L	Polygala tricornis	[37]
257	3-O-(E)-Sinapoyl-[4-O-(E)-feruloyl]-β-d-fructo-furanosyl-(2→1)-[β-d-glucopyranosyl-(1→4)-β-d-glucopyranosyl-(1→2)]-[6-O-(E)-sinapoyl] -α-d-glucopyranoside or tricornose K	Polygala tricornis	[37]
258	3-O-(E)-sinapoyl-[4-O-(E)-sinapoyl]-β-d-fructo-furanosyl-(2→1)-[β-d-glucopyranosyl-(1→4)-β-d-glucopyranosyl-(1→2)]-[6-O-(E)-sinapoyl]-α-d-glucopyranoside or tricornose H	Polygala tricornis	[37]
259	3-O-(E)-3,4,5-Trimethoxylcinnamoyl-[4-O-(E)-feruloyl]-β-d-fructofuranosyl-(2→1)-[β-d-gluco-pyranosyl-(1→4)-β-d-glucopyranosyl-(1→2)]-[6-O-(E)-sinapoyl]-α-d-glucopyranoside or tricornose J	Polygala tricornis	[37]
260	3-O-(E)-3,4,5-Trimethoxylcinnamoyl-[4-O-(E)-sinapoyl]-β-d-fructofuranosyl-(2→1)-[β-d-glucopyranosyl-(1→4)-β-d-glucopyranosyl-(1→2)]-[6-O-(E)-sinapoyl]-α-d-glucopyranoside or tricornose I	Polygala tricornis	[37]
261	Senegose I	Polygala senega var. latifolia Torr. Et Gray	[105]
262	1-O-(E)-p-Coumaroyl-(3-O-benzoyl)-β-d-fructo-furanosyl-(2→1)-[β-d-glucopyranosyl-(1→2)]-[6-O-acetyl-β-d-glucopyranoysl-(1→3)]-[4-O-(E)-feruloyl]-(6-d-acetyl)-α-d-glucopyranoside or glomeratose F	Polygala glomerata	[38]
263	1-O-(E)-p-Coumaroyl-(3-O-benzoyl)-β-d-fructo-furanosyl-(2→l)-[β-d-glucopyranosyl-(1→2)]-[6-O-acetyl-β-d-glucopyranoside-(1→3)]-{4-O-[4-O-β-d-glucopyranosyl-(E)-feruloyl]}-[6-O-(E)-p-coumaroyl]-α-d-glucopyranosyl or glomeratose G	Polygala glomerata	[38]
264	1-O-p-coumaroyl-(3-O-benzoyl)-β-d-fructo-furanosyl-(2→1)-[β-d-glucopyranosyl-(1→2)]-[6-O-acetyl-β-d-glucopyranosyl-(1→3)]-(4-O-p-coumaroyl)-α-d-glucopyranoside or fallaxose C	Polyyala fallax	[92]
265	Reiniose G	Polygala glomerata; Polygala reinii Fr. et Sav	[38,46]
266	Dalmaisiose H	Polygala dalmaisiana	[93]
267	1-O-p-Coumaroyl-(3-O-benzoyl)-β-d-fructo-furanosyl-(2→1)-[β-d-glucopyranosyl-(1→2)]-[6-O-acetyl-β-d-glucopyranosyl-(1→3)]-(4-O-feruloyl)-α-d-glucopyranoside or fallaxose D	Polyyala fallax	[92]
268	Dalmaisiose J	Polygala dalmaisiana	[93]
269	Dalmaisiose L	Polygala dalmaisiana	[93]
270	Dalmaisiose M	Polygala dalmaisiana	[93]
271	Reiniose H	Polygala reinii Fr. et Sav	[46]
272	Senegose G	Polyyala fallax; Polygala senega var. latifolia Torr. Et Gray	[92,105]
273	Senegose H	Polygala senega var. latifolia Torr. Et Gray	[105]
274	Senegose F	Polygala reinii Fr. et Sav; Polygala senega var. latifolia Torr. Et Gray	[46,105]
275	3-O-β-D-Glucopyranosylpresenegenin 28-O-β-D-xylopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→2)-{4-O-[(E)-3,4-dimethoxycinnamoyl]}-β-D-fucopyranosyl ester or Polygalasaponin XLII	Polygala glomerata Lour	[106]
276	3,4-Dihydroxy-β-phenylethyl-O-α-l-rhamno-pyranosyl-(1→2)-O-[O-β-d-glucopyranosyl-(1→4)-β-d-glucopyranosyl-(1→6)]-3-O-caffeoyl-β-d-allopyranoside or magnoloside C	Magnolia obovata Thunb	[62]
278	3-O-{4-O-[β-d-Glucopyranosyl-(1→3)-(2-O-acetyl)-α-l-rhamnopyranosyl]-feruloyl}-β-d-fructo-furanosyl-(2→1)-(4,6-di-O-benzoyl)-α-d-gluco-pyranoside or fallaxose B	Polyyala fallax	[92]
279	2-(3,4-Dihydroxyphenyl)ethyl O-β-apio-furanosyl-(1→6)-O-[O-β-apiofuranosyl-(1→4)-α-rhamnopyranosyl-(1→3)]-4-O-(E)-caffeoyl-β-glucopyranoside or lunariifolioside	Phlomis lunariifolia	[106]
280	Tenuifoliose K	Polygala tenuifolia Willd	[11]
281	Tenuifoliose J	Polygala tenuifolia Willd	[11]
282	tenuifoliose I	Polygala tenuifolia Willd	[11]
283	Tenuifoliose H	Polygala tenuifolia Willd	[11]
284	Tenuifoliose C	Polygala tenuifolia Willd; Polyyala fallax	[12,92]
285	Tenuifoliose B	Polygala tenuifolia Willd	[12]
286	Tenuifoliose D	Polygala tenuifolia Willd; Polygala reinii Fr. et Sav	[12,46]
287	Tenuifoliose E	Polygala tenuifolia Willd	[12]
288	Tenuifoliose A	Polygala tenuifolia Willd	[11,12]
289	Tenuifoliose P	Polygala tenuifolia Willd	[11]
290	Tenuifoliose O	Polygala tenuifolia Willd	[11]
291	Reiniose I	Polygala reinii Fr. et Sav	[46]
292	Tenuifoliose N	Polygala tenuifolia Willd	[11]
293	Reiniose J	Polygala reinii Fr. et Sav	[46]
294	1-O-Feruloyl-(3-O-benzoyl)-β-d-fructofuranosyl-(2→1)-[β-d-glucopyranosyl-(1→2)]-[β-d-gluco-pyranosyl-(1→3)-(6-o-acetyl)-β-d-gluco-pyranosyl-(1→3)]-(6-o-feruloyl)-α-d-glucopyranoside or fallaxose E	Polyyala fallax	[92]
295	Senegose K	Polygala senega L.	[107]
296	Senegose J	Polygala senega L.	[107]
297	Senegose N	Polygala senega L.	[107]
298	Senegose O	Polygala senega L.	[107]
299	Senegose M	Polygala senega L.	[107]
300	Senegose L	Polygala senega L.	[107]
301	Senegose D	Polygala senega var. latifolia Torr. Et Gray	[108]
302	Senegose C	Polygala senega var. latifolia Torr. Et Gray	[108]
303	Senegose B	Polygala senega var. latifolia Torr. Et Gray	[108]
304	Senegose A	Polygala senega var. latifolia Torr. Et Gray	[108]
305	Senegose E	Polygala senega var. latifolia Torr. Et Gray	[108]
306	Dalmaisiose D	Polygala dalmaisiana	[93]
307	Dalmaisiose B	Polygala dalmaisiana	[93]
308	Dalmaisiose E	Polygala dalmaisiana	[93]
309	Dalmaisiose I	Polygala dalmaisiana	[93]
310	Dalmaisiose N	Polygala dalmaisiana	[93]
311	Dalmaisiose F	Polygala dalmaisiana	[93]
3312	Dalmaisiose P	Polygala dalmaisiana	[93]
313	Dalmaisiose G	Polygala dalmaisiana	[93]
314	Dalmaisiose C	Polygala dalmaisiana	[93]
315	Dalmaisiose K	Polygala dalmaisiana	[93]
316	Dalmaisiose O	Polygala dalmaisiana	[93]
317	E-Senegasaponin b	Polygala senega L.var. latifolia Torrey et Gray	[109]
318	Z-Senegasaponin b	Polygala senega L.var. latifolia Torrey et Gray	[109]
319	Senegin II	Polygala glomerata Lour	[106]
320	(Z)-Senegin II	Polygala glomerata Lour	[106]
321	Tenuifoliose M	Polygala tenuifolia Willd	[11]
322	Tenuifoliose L	Polygala tenuifolia Willd	[11]
323	Tenuifoliose G	Polygala tenuifolia Willd	[11]
324	Tenuifoliose F	Polygala tenuifolia Willd	[11,12]
325	3-O-β-d-Glucopyranosylpresenegenin 28-O-β-d-galactopyranosyl-(1→4)-β-d-xylo-pyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→2)[β-d-glucopyranosyl-(1→3)]-(4-O-[(E)-3,4-dimethoxycinnamoyl]}-8-O-fucopyranosyl ester or polygalasaponin XLIV	Polygala glomerata Lour	[106]
326	3-O-β-d-Glucopyranosylpresenegenin 28-O-β-d-galactopyranosyl-(1→4)-β-d-xylopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→2)-[6-O-acetyl-β-d-glucopyranosyl-(1→3)]-{4-O-[(E)-3,4-dimethoxycinnamoyl])-β-d-fucopyranosyl ester or polygalasaponin XLV	Polygala glomerata Lour	[106]
327	3-O-β-d-Glucopyranosylpresenegenin 28-O-β-d-galactopyranosyl-(1→4)-β-O-xylopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→2)-[6-O-acetyl-β-d-glucopyranosyl-(1→3)]-{4-O-[(Z)-3,4-dimethoxycinnamoyl]}-β-d-fucopyranosyl ester or polygalasaponin XLVI	Polygala glomerata Lour	[106]
328	3-O-β-d-Glucopyranosylpresenegenin, 28-O-β-d-galactopyransyl(1→4)-β-d-xylopyranosyl -(1→4)-α-l-rhamnopyranosyl-(1→2)-{4-O-p-methoxycinnamoyl]}-[β-d-glucopyranosy l(1→3)]-β-d-fucopyranosyl ester or polygalasaponin X X X	Polygala japonica Houtt.	[56]
329	3-O-β-d-Glucopyranosylpresenegenin 28-O-β-d-galactopyranosyl-(1→4)-β-d-xylo-pyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→2)-[α-l-arabinopyranosyl-(1→3)]-[4-O-(E)-p-methoxycinnamoyl]-β-d-fucopyranosyl ester or polygalasaponin XLIII	Polygala glomerata Lour	[106]
330	3-O-β-d-Glucopyranosylpresenegenin 28-O-α-l-arabinopyransyl (1→4)-β-d-xylopyranosyl-(1→4)-[β-d-apiofuranosyl-(1→3)]-α-l-rhamnopyranosyl-(1→2)-[4-O-3,4,5-trimethoxy-cinnamoyl]-β-d-fucopyranosyl ester or polygalasaponin XXXI	Polygala japonica Houtt.	[56]
331	E-Senegasaponin a	Polygala senega L.var. latifolia Torrey et Gray	[109]
332	Z-Senegasaponin a	Polygala senega L.var. latifolia Torrey et Gray	[109]
333	1-O-(E)-p-Coumaroyl-(3-O-benzoyl)-β-d-fructo-furanosyl-(2→1)-[6-O-(E)-feruloyl-β-d-gluco-pyranosyl-(1→2)]-[6-O-acetyl-β-d-gluco-pyranosyl-(1→3)-(4-O-acetyl)-β-d-glucopyranosyl-(1→3)]-4-O-[4-O-α-l-rhamnopyranosyl-(E)-p-coumaroyl]-α-d-glucopyranoside or polygalajaponicose I	Polygala japonica	[110]
334	3-O-β-d-Glucopyranosylpresenegenin 28-O-α-L-arabinopyransyl-(1→4)-β-d-xylo-pyranosyl-(1→4)-[β-d-apiofuranosyl-(1→3)]-α-l-rhamnopyranosyl-(1→2)-[4-O-p-methoxy-cinnamoyl]-[α-l-rhamnopyranosyl(1→3)]-β-d-fucopyranosyl ester or polygalasaponin XXXII	Polygala japonica Houtt.	[56]

Up to now, there has been no detailed research on the extraction procedures for these chemical constituents. Generally, the crude extracts wer prepared with different concentrations of methanol, ethanol or acetone-water solution by the impregnation method, refluxing extraction or decoction method [10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111]. Then the extracts were evaporated in a rotary evaporator to yield a syrupy residue. This residue was suspended in H2O and extracted successively with petroleum ether, CHCl3, EtOAc and H2O-satd n-BuOH [10,14,15,22]. The different extracts were then fractionated on different chromatographic columns with different mobile phases. Thereinto, silica gel CC was the most commonly used positive phase chromatographic column and eluted with petroleum ether, petroleum ether–EtOAc CHCl3–EtOAc, CHCl3–MeOH, CHCl3–MeOH–H2O with various ratios [10,11,22,30]. Mitsubishi Diaion HP-20, Diaion HP20SS, Chromatorex ODS, different types of macroporous resin and MCI columns were the reverse phase chromatography columns, which were used widely, eluted with a step-gradient of MeOH–H2O or EtOH–H2O (10%–100%), respectively. Sephadex LH-20 was also commonly used [19,31]. Some oligosachariches were isolated by preparative HPLC (Develosil Lep-ODS) [11]. Preparative TLC and recycle semi-preparative HPLC were often used to further purify samples [15].

2.1. Monosaccharide Esters

The 27 monosaccharide [16,18,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35] esters 1–10, 21–27 represent the simplest structures found among CASEDs (Figure 1, Figure 2, Figure 3, Figure 4 and Figure 5). The main structural moiety of these compounds (Figure 2 and Figure 5), is a β-d-glucose ester, or an α-l-rhamnose ester in compounds 11–15 (Figure 3). Compounds 16–20 exist as anomeric mixtures in solution and the phenylacrylic group is often attached at the C-6 position of the glycosyl moiety. Coincidentally, compounds 11–15 possess the same p-methoxy- cinnamoyl group attached to the rhamnose unit though an ester bond in the monosaccharide ester. Compounds 2, 4 and 20 are phenylpropanol esters linked with glucose as the important part. Compounds 1 and 3 contain two different phenylpropanols attached to one glucose molecule. Ningposide D (14) [16] is also an anomeric mixture of rhamnose esters and the anomeric ration α/β is 3:1, here it was drawn as the α-l-rhamnose ester. Isolated from the underground parts of Globularia orientali, globularitol (21) has a carbohydrate chain moiety, formed by a glucitol group. It has the ability to efficiently scavenge free radicals [32]. Grayanin (22) has a mandelonitrile unit connected at the C-1 position in the glucose. This compound is a unique cyanogenic glycoside among CASEDs [20]. The benzeneacetonitrile group of grayanin may be originated from phenylalanine from the biosynthetic pathway viewpoint. Up to now, paederol A (25) and B (26), are the only two reported CASEDs with acyclic sugars. By the way, paederol A and B did not exhibit obviously cytotoxicity in the Lu1 (lung cancer), LNCaP (prostate cancer) and MCF-7 (breast cancer) [34]. Kaempferol 3-O-β-d-(6-O-p-E-coumaroyl)-glucopyranoside (27) is the only flavonoid of CASEDs, which possess inhibitory activity towards a drug-metabolizing enzyme, CYP3A4 [35].

Figure 2

Structures of compounds 1–10.

Figure 3

Structures of compounds 11–15.

Figure 4

Structures of compounds 16–20.

Figure 5

Structures of compounds 21–27.

2.2. Disaccharide Esters

Disaccharide esters 28–162 (Figure 6, Figure 7, Figure 8, Figure 9, Figure 10, Figure 11, Figure 12, Figure 13, Figure 14, Figure 15 and Figure 16) [4,5,10,13,15,17,19,24,25,29,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91] constitute the largest group among CASEDs. Their glycosyl parts include glycosyl groups, with glucopyrannosyl, rhamnopyranosyl, fructofuranosyl, and arabinopyranosyl ones being the most important and sucrose units as found in compounds 28–120, 162 are more rare,. Among them, the glycosyl unit in 28–120 has the anomeric carbon on α-d-glucose linked to a β-d-fructose. The ester bond is often formed at the C-6 position of α-d-glucose and C-3 position of β-d-fructose. The compounds 122–140 are composed of α-l-rhamnose and β-d-glucose, with a connection between the C-1 location of α-l-rhamnose and C-3 position of β-d-glucose. The cinnamic acid unit is mainly connected to the C-4 position of β-d-glucose, and less often in the C-6 location. The glycosyl moieties of compounds 145–147 are similar to those of 122–140, and the configuration of the hydroxyl attached to the anomeric carbon of glucose could not be determined. The aglycone part of compounds 150–155 is two β-d-glucoses joined by C-1 and C-6, and the functional group is attached to the C-2 position of the parent nucleus.

Figure 6

Structures of compounds 28–120.

Figure 7

Structure of compound 121.

Figure 8

Structures of compounds 122–140.

Figure 9

Structure of compound 141.

Figure 10

Structures of compounds 142–143.

Figure 11

Structure of compound 144.

Figure 12

Structures of compounds 145–147.

Figure 13

Structure of compound 148.

Figure 14

Structure of compound 149.

Figure 15

Structures of compounds 150–155.

Figure 16

Structures of compounds 156–162.

Sibiricose A5 (28), tenuifoliside A (51) and DISS (73) from the root of Polygala sibirica (Yuanzhi) [13], have the same core sucrose unit and the ester is always connected at the C-6 position of α-d-glucose and C-3 position of β-d-fructose. These compounds have anti-depression properties. In 1968, verbascoside (=acteoside 131) was the first CASED isolated from the medical plant Syringa vulgaris (Oleaceae) [3]. So far, it has been reported in nine families. Magnoloside A (121) from medicinal plants of the Magnoliaceae family is unique among the phenylpropanoids in rarely occurring alone as the core glycosyl [62]. In addition, crenatoside (157) has a novel annular framework which attaches the C-1 and C-2 of the glucose to a hexatomic oxygen ring [91]. Glomeratose E (162) possesses a (E,E)-β,β′-bis-sinapoyl group between the α-d-glucose and β-d-fructose [38].

2.3. Trisaccharide Esters

Ninety three compounds 163–254 [5,19,21,24,37,46,51,55,63,64,65,66,67,75,78,79,80,81,82,83,84,85,86,93,94,95,96,97,98,99,100,101,102,103,104] represent the trisaccharide ester category. They are mainly obtained from the Scrophulariaccae plant family. The most common glycosyl moieties are sucrose, with glucose as core unit (compounds 163–174, 175, Figure 17, Figure 18, Figure 19 and Figure 20 and Figure 21), di-apiose combined with glucose (176–178, Figure 22 and Figure 23), glucose as the kernel glycosyl (179–246, 247–248, Figure 24, Figure 25, Figure 26, Figure 27, Figure 28, Figure 29, Figure 30, Figure 31, Figure 32, Figure 33, Figure 34, Figure 35, Figure 36, Figure 37, Figure 38, Figure 39, Figure 40, Figure 41, Figure 42, Figure 43, Figure 44, Figure 45, Figure 46, Figure 47, Figure 48, Figure 49, Figure 50, Figure 51 and Figure 52 and Figure 53), and rhamnose as the central part with its terminal carbon combined with glucose and the C-3 connected with xylose (249–254, Figure 54). The phenylpropanoid groups usually esterify the C-3 and C-4 positions of fructose, C-3, C-4 and C-6 of glucose and C-4 of rhamnose. Tricornoses E (165) and F (166) from the Polygalaceae family possess two different phenylpropanoids attached to one fructose molecule [37]. Lilongiside (173), reiniose D (174) and hydrangeifolin II (253) differ from other trisaccharide esters in that their three sugar cores are not combined as a whole chain [21,46,55]. The aglycone groups of lilongiside and reiniose D are sucrose with glucose, rhamnose. Hydrangeifolin II is composed of caffeoyl glycoside with a diglycosyl unit esterified with an ester linkage. This compound has a weak DPPH free radical scavenging activity. Teucrioside (229) from the Labiatae family is the only CASED that has a lyxose moiety, rarely occuring in higher plants [101]. The anomeric carbon configuration of glucose unit in ligupurpuroside F (234) is not determined [24]. Rossicaside F (254) exists as epimers at the β-C of the phenethyl alcohol moiety (R,S-β-OEt) [98].

Figure 17

Structures of compounds 163–166.

Figure 18

Structures of compounds 167–168.

Figure 19

Structures of compounds 169–172.

Figure 20

Structures of compounds 173–174.

Figure 21

Structure of compound 175.

Figure 22

Structures of compounds 176–177.

Figure 23

Structure of compound 178.

Figure 24

Structures of compounds 179–182.

Figure 25

Structures of compounds 183–187.

Figure 26

Structures of compounds 188–192.

Figure 27

Structure of compound 193.

Figure 28

Structures of compounds 194–195.

Figure 29

Structure of compound 196.

Figure 30

Structures of compounds 197–201.

Figure 31

Structures of compounds 202–205.

Figure 32

Structures of compounds 206–207.

Figure 33

Structures of compounds 208–213.

Figure 34

Structures of compounds 214–216.

Figure 35

Structures of compounds 217–218.

Figure 36

Structure of compound 219.

Figure 37

Structure of compound 220.

Figure 38

Structures of compounds 221–223.

Figure 39

Structure of compound 224.

Figure 40

Structures of compounds 225–227.

Figure 41

Structure of compound 228.

Figure 42

Structure of compound 229.

Figure 43

Structure of compound 230.

Figure 44

Structures of compounds 231–232.

Figure 45

Structures of compounds 233–234.

Figure 46

Structures of compounds 235–238.

Figure 47

Structures of compounds 239–240.

Figure 48

Structures of compounds 241–242.

Figure 49

Structure of compound 243.

Figure 50

Structure of compound 244.

Figure 51

Structure of compound 245.

Figure 52

Structure of compound 246.

Figure 53

Structures of compounds 247–248.

Figure 54

Structures of compounds 249–254.

2.4. Tetrasaccharide Esters

Of all the tetrasaccharide esters 255–279 (Figure 55, Figure 56, Figure 57, Figure 58, Figure 59 and Figure 60) [37,38,46,62,92,93,105,106,107], 23 are found in Polygalaceae plants Most of the phenylacrylic moieties are coumaroyl, feruloyl and sinapoyl groups. According to the core glycosyl type, these compounds can be classified into four groups, including the combination of fructose with three glucoses (255–274, Figure 55, Figure 56 and Figure 57), rhamnose, fructose with two glucoses (277–278, Figure 60), the other tetrasaccharide esters (275, 276, 279, Figure 58, Figure 59 and Figure 60). Senegoses F–I (261, 272–274) [105], whose absolute configurations were established by spectroscopic and chemical means, were purified from Polygala senega var. latifolia ToRR. et GRAY(Polygalaceae). Polygalasaponin XLII (275) which was obtained from the roots of Polygalaglomerata Lour belongs to the oleanane-type saponins, [107]. Its fucose C-4 position attaches to a 3,4-dimethoxycinnamoyl by an ester bond. The structures of fallaxose A (277) and fallaxose B (278), found in the roots of Polygala fallax, are similar, except for the acetyl group and the glucose location. Both are esterified with ferulic acid [92].

Figure 55

Structures of compounds 255–260.

Figure 56

Structure of compound 261.

Figure 57

Structures of compounds 262–274.

Figure 58

Structure of compound 275.

Figure 59

Structure of compound 276.

Figure 60

Structures of compounds 277–279.

2.5. Other Sugar Esters

To our knowledge, pentasaccharide esters 280–320 (Figure 61, Figure 62, Figure 63 and Figure 64) [11,12,46,92,93,107,108,109,110], hexsaccharide esters 321–333 (Figure 65, Figure 66, Figure 67, Figure 68, Figure 69, Figure 70 and Figure 71) [11,12,56,107,109,110], heptasaccharide esters 334 (Figure 72) [56] were all found in the Polygalaceae family and most of them form a series of similar type compounds. That is to say, CASEDs with higher carbon numbers are rarely found in plants outside the Polygalaceae. The phenylacrylic groups usually locate at C-1 of fructose, C-4 of glucose, as well as C-4 of fucose. Most glycosyl moieties of pentasaccharide esters are four glucoses and a fructose with different locations and sequence. Tenuifolioses A and B (285, 288), obtained from Polygala tenuifolia Willd, showed neuroprotective activity. Tenuifolioses A and B have the same glycosyl core, with β-d-glucoses connected at the C-1 and C-4 position and the first glucose combined with another glucose at C-2 and β-d-fructose at C-1 [12]. Compounds 280–294 with this same sugar core serve to remind researchers of the need for more studies on these compounds to find more precursor compounds of anti-depression drugs. The tenuifoliose A–E (284–288), senegose A–E (301–305), J–O (295–300) type of oligosaccharide multi-esters are esterified with coumaric and ferulic acids [108,111]. Compounds 306–307, 311 [93] are pentasaccharide esters having the same glycosyl connection sequence as that of reiniose G (265) and have a p-coumaroyl residue at C-6 of glucose [38]. Compounds 308–310, 312–316 are also pentasaccharide esters, but with a feruloyl residue at C-6 of glucose. Compounds 319–320 and 325–330 are CASEDs belonging to the oleanane-type saponins and found in the root parts of Polygala glomerata Lour [107], which have the same parent nuclei as polygalasaponin XLII (275). To our knowledge, only one heptasaccharide ester (polygalasaponin XXXII, 334) was reported, and it is also an oleanane-type saponin, with hippocampus-dependent learning and memory enhancing activity. Polygalasaponin XXXII [56], as the representative of oleanane-type saponins in CASEDs, has also captured attention of researchers to do more investigation on the other compounds of the class (317–320, 325–332) in order to identify compounds with the same activity or with more sugars that might improve the improve hippocampus-dependent learning and memory enhancing activity of polygalasaponin XXXII.

Figure 61

Structures of compounds 280–294.

Figure 62

Structures of compounds 295–305.

Figure 63

Structures of compounds 306–316.

Figure 64

Structures of compounds 317–320.

Figure 65

Structures of compounds 321–322.

Figure 66

Structures of compounds 323–324.

Figure 67

Structures of compounds 325–328.

Figure 68

Structure of compound 329.

Figure 69

Structure of compound 330.

Figure 70

Structures of compounds 331–332.

Figure 71

Structure of compound 333.

Figure 72

Structure of compound 334.

3. Biological Activities

To date, approximately 334 CASEDs have been isolated from various medicinal plants and their structures characterized. However, the biological activities, mechanism of action and structure-activity-relationships (SAR) of many CASEDs have rarely been explored up to now. Hence, an overview of the pharmacological activities of the CASED may serve as valuable indication to further probe into their full therapeutic potentials.

3.1. Anti-Depression Activity and Neuroprotective Activity

Depression, one of the major mental disorders, is accompanied by symptoms such as emotional slump, reduced physical activities, feelings of helplessness and pessimism and even suicide attempts. At present there are three main points of view regarding the pathogenesis of depression, including the biogenic amine theory, the nerve nutrition theory and the cytokines theory.

Sibiricose A5 (28), tenuifoliside A (51), 3′,6-disinapoylsucrose (DISS, 73), tenuifoliside B (52), buergerisides A1 (13), B1 (12), B2 (15) and C1 (11), tenuifolioses A (285) and B (288) show obvious antidepressant activity [10,12,13,18]. Sibiricose A5 (28) and tenuifoliside A (51), extracted from Chinese herbal medicine Polygala tenuifolia Willd, were found to dramatically protect PC12 cells damaged by glutamate [9]. Tenuifolioses A (285) and B (288) showed neuroprotective activity against glutamate and serum deficiency at a concentration of 1 × 10−5 mol·L−1 [12]. Liu et al. [1] discovered that DISS and tenuifoliside A (TEA, 51), isolated from Radix Polygalae, showed protective effects on SH-SY5Y against Cort-induced injury. A study by Ikeya et al. [112] showed that tenuifoliside B (52) improved the scopolamine-induced impairment of passive avoidance response by promoting the cholinergic system. Buergerisides A1 (13), B1 (12), B2 (15) and C1 (11) from the roots of Scrophularia buergeriana exhibit protective activity on primary cultures of rat cortical cells after exposure to excitotoxin, glutamate according to an investigation by Kim et al. [18].

Further findings demonstrate that a possible mechanism of the antidepressant action of DISS maybe be related with hippocampal neuroplasticity and neuroproliferation. DISS possesess potent and rapid antidepressant activity, which are mediated via brain MAO-A and MAO-B activity and upregulated serum cortisol levels induced by CMS [113]. In neuronal cells, DISS-mediated regulation of BDNF gene expression is associated with CREB-mediated transcription of BDNF upstream activation of ERK1/2 and CaMKII to cause neuroprotective and antidepressant effects [114]. Dong et al. [8] discovered that the neurotrophic mechanism of TEA (b24) in C6 cells correlates with TrkB/BDNF/ERK and TrkB/BDNF/PI3K.

3.2. Anticancer Activity

Belonging to the family of serine/threonine protein kinases that are activated by Ca2+, Protein Kinase C (PKC) is involved in signal transduction, and cellular proliferation and differentiation. It also plays an important role in cell cycle control, tumor genesis, antitumor drug resistance and apoptosis. PKC has been proved to be related with the activation of HIV-1 gene expression, tumor promotion, and the inhibition of apoptosis in leukemia cells. Therefore, it makes a lot of sense to find chemical compounds from natural plants to inhibit the activity of PKC [50,54].

Takasaki et al. found that vanicoside A (102) and vanicoside B (67) from Polygonum pensylvanirum inhibited PKC activity with IC50 values of 44 μg/mL and 31 μg/mL, respectively [54]. After this preliminary work, LaVerne et al. [50] continued the isolation work on this plant in order to obtain possible homologues via HPLC-MS and isolated vanicosides C-F (104, 57, 113, 91). Regretfully, LaVeme did not to do much research on the pharmacological activity of the vanicosides. Notably, acteoside (=verbascoside, 131) from Lantana camara also shows PKC inhibitory activity in the rat brain with an IC50 of 25 μM [29]. With the widest distribution in the plant kingdom, acteoside has been widely applied to treat diseases such as cancer, inflammation, or immune disorders.

In the virus family, the Epstein-Barr virus (EBV) is a type of herpes virus causing cancer. EBV has been considered one of the causes of many kinds of malignant tumors such as nasopharyngeal carcinoma. EBV infection mainly occurs human oropharyngeal epithelial cells and B lymphocytes. Lapathoside A (63), lapathoside D (31), vanicoside B (67) and hydropiperoside (37) exhibit remarkable inhibitory effects on the EBV, which is early antigen induced by tumor-promoters, so it makes sense to focus on these four compounds as worthy anti-tumor-promoters for cancer chemoprevention [2,39].

Meanwhile, Takasaki et al. [39] reported that lapathoside A (63) and vanicoside B (67) inhibited two-stage carcinogenesis induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Moreover, vanicoside B exhibits remarkable inhibitory effects, which are initiated with a NO (nitric oxide) donor and NOR-1((±)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexenamide).

Smilaside D (40), smilaside E (47) and smilaside F (99) displayed cytotoxicity against human colon tumor (DLD-1) cells (ED50 = 2.7, 4.5, 5.0 μg/mL), and smilaside A (79) showed weak cytotoxicity against DLD-1 cells (ED50 = 11.6 μg/mL). Furthermore, smilaside A (79), smilaside B (107), smilaside D, smilaside E and smilaside F displayed weak cytotoxicity (ED50 = 5.1–13.0 μg/mL) on three to six human tumor cell lines, consisting of human cervical carcinoma (Hela), human oral epithelium carcinoma (KB), DLD-1, human medulloblastoma (Med) cells, human lung carcinoma (A-549) and human breast adenocarcinoma (MCF-7) [14].

3.3. Antioxidant Activity

Plenty of CASEDs were found to possess antioxidant activities, mainly related to their substituted acid groups. The antioxidant properties of these compounds were tested by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays. Probably thanks to the presence of the 3,4-dihydroxy (catechol) moiety in the structure, compound 2 showed significant antioxidant activities, compared to caffeic acid [21]. Compound 21 from Globularia orientalis also exhibited antioxidant potential, indicating that it could efficiently scavenge free radicals [32].

Zhang et al. [15] found that smilasides G–L (38, 106, 46, 41, 105, 42) showed moderate scavenging activities against DPPH radicals and smilasides J–L (41, 105, 42) exhibited stronger antioxidant activity, which was quite similar to that in positive control ((±)-α-tocopherol). These results support the idea that the substituted feruloyl group plays a key role in the antioxidant activity of phenylpropanoid sugar esters. Heterosmilaside (95), helonioside B (45) and compound 98 showed strong antioxidant DPPH radical scavenging activity with IC50 values of 12.7, 9.1 and 8.7 µg/mL, respectively [46]. Compounds 28, 32 and 44 exhibited higher activity on scavenging the DPPH radical, compared to l-cysteine at the concentration of 0.02 mM, and the antioxidant activity of compound 32 was almost as same as that of α-tocopherol [36]. Compound 62 and verbascoside showed antioxidant potential pointing out their ability to efficiently scavenge free radicals. 6-O-Sinapoyl sucrose (75) showed weak activity in the DPPH test, but in the superoxide scavenging test, its antioxidative activity increased slightly, hence, a sucrose moiety esterified by sinapic acid seems to regulate the antioxidative activity [115]. Lapathoside D (31) showed DPPH radical scavenging activity with an IC50 of 0.088 mM [3]. Kiem et al. [53] found that vanicoside A (102), hydropiperoside B (103) and vanicoside E (113) exhibited significant DPPH radical scavenging properties, with IC50 values of 23.4, 26.7 and 49.0 µg/mL, respectively. However, compounds 66, 67 and 113 were inactive, probably due to the non-existence of acetyl groups in their molecules compared with 102, 103 and 113. Wang et al. discovered that diboside A (58) and lapathoside A (63) only showed low activities in the DPPH test [51].

Ehrenoside (183), verpectoside A (185), B (193) and C (194) were isolated from the aerial parts of Veronica pectinata var. glandulosa. They revealed potent radical scavenging activity against DPPH radical. Ehrenoside and verpectoside B were more active than 3-tert-butyl-4-hydroxyanisole (BHA) and had comparable activity to all dl-α-tocopherol [104]. Hamerski et al. reported that the antioxidant activity of compound 2 (IC50 values 15.0 μM) was comparable to that of the positive control caffeic acid, while compound 253 possess only weak activity [21].

In the study of Wang et al. [116], compound 59 possessed modest activity, with an IC50 of 20.1 µM in the DPPH radical scavenging test and in the metmyoglobin assay it had antioxidative activity comparable with Trolox (3.70 Trolox equivalents). Quiquesetinerviusides A-E (86, 87, 115, 85 and 114) exhibited low DPPH scavenging activity, but considerable·OH radical scavenging activity (IC50 8.4 ± 1.1, 6.8 ± 1.0, 7.4 ± 1.0, 5.5 ± 0.9, 3.6 ± 0.8 µM, respectively) [4]. Hosoya et al. [89] used ESR to evaluate the effect on superoxide anion radicals (O2−) of compounds 154, 150, 155, 153 and they exhibited IC50 values of 28.5, 84.5, 8.4, 17.1 µM, respectively, using ascorbic acid (IC50 value 140 µM) as a positive control.

3.4. Antiinflammatory Activity

Antiinflammatory activity referes to the removal of inflammation or swelling. Acteoside (131), angoroside A (196) and angoroside C (200) revealed a considerable effect in the TXB2-release assay. Angoroside A (196), angoroside D (199), acteoside (131) and isoacteoside (128) significantly inhibited LPS-induced PGE2, NO and TNF-α in a concentration-dependent manner. In LPS-stimulated macrophages, angoroside C (200) only had activity on NO [63,70]. Acteoside (131) had strong in vitro and in vivo anti-inflammatory effects, whilst isoacteoside (128) was found to have modest activity. Pretreatment with 1–50 μM CASED (compounds 131, 157, 220) concentration-dependently diminished phorbol-12-myristate-13-acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced reactive oxygen species (ROS) production with IC50 values of approximately 6.8–23.9 and 3.0–8.8 μM, respectively [117]. The anti-inflammatory activities of quiquesetinerviusides D (85) and E (114) were evaluated in RAW 264.7 cells. Both of them exhibited strong activities against LPS-stimulated NO production. And the outcome showed inhibition of quiquesetinerviuside D and E (IC50 9.5, 9.2 µM) compared with a positive control, quercetin (IC50 34.5 µM). In vitro cyclooxygenase (COX) catalyzed prostaglandin biosynthesis inhibition assay, compounds 131,205, 218 and these compounds exhibited stronger inhibitory potencies on Cox-2 than Cox-1 (131,205, 218 IC50 on Cox-2 at 0.69, 0.49 and 0.61 mM, respectively).

3.5. Antiviral Activity

Niruriside (109) has particular inhibitory activity with an IC50 value of 3.3 μM, against the binding of regulation of virion expression (REV) protein to responsive element (RRE) RNA [60]. Kernan et al. [69] reported that verbacteoside (131), isoverbascoside (128), luteoside A (188) and luteoside B (189) exhibited antiviral activity (EC50) in an in vitro assay against respiratory syncytial virus (RSV), which was resembled or better than that of ribavirin, a drug used to cure RSV contagion in humans. Furthermore, these compounds also showed better activity against RSV than ribavirin. Verbascoside (131) exhibited antiviral activity against vesivular stomatitis virus (VSV), but was inactive against herpes simplex type I (HSV-1). The non-toxic confining cellular viability concentration for the activity was 53.6% at 500 μg/mL [118].

3.6. Other Activities

Compounds 138,131, 159, 158 isolated from Paulownia tomentosa stems were texted for in vitro cytotoxity against Streptococcus pyogenes (A308 and A77), Staphylococcus aureus (SG511, 285 and 503), Streptococcus faecium MD8b, etc. All the compounds exhibited remarkable antibacterial activity. Compound 159 showed a minimal inhibitory concentration (MIC) value of 150 μg/mL against Staphylococcus and Streptococcus species [76]. A mixture of poliumoside (216) and lamalboside (227) revealed moderate antibacterial activity. Compounds 130, 205 and 218 also possess antimicrobial activity [119]. Vanicoside A (102) and B (67) showed β-glucosidase inhibitory activity, with IC50 values of 59.8 and 48.3 μg/mL (59.9 and 50.5 μM), respectively [120]. The activity of forsythoside B (205) and alyssonoside (206) against free radical-induced impairment of endothelium-dependent relaxation in isolated rat aorta was investigated. Both provided partial protection at 10−4 M concentration against the electrolysis-induced inhibition acetylcholine response [121]. Senegin II (319) was tested for hypoglycemic activity in normal and KK-Ay mice. Under similar conditions, senegin II not only reduced the level of blood glucose in normal mice 4 h after intraperitoneal administration, but also significantly lowered the blood glucose level of KK-Ay mice [122]. Tenuifolioses B (288), and C (284) potentiated basal synaptic transmission in the dentate gyrus of anesthetized rats [12]. The only septsaccharide ester, polygalasaponin XXXII (334), could improve hippocampus-dependent learning and memory. The result suggests that it may be through the enhancement of synaptic transmission, activation of the MAP kinase cascade and improvement of BDNF level [56].

The rhizome extracts of Smilax glabra Rox B., which is called tufuling in Traditional Chinese Medicine, show many kinds of pharmacological activities like hypoglyceaemic, immuno- modulatory, free-radical scavenging and antioxidant enzyme fortifying activities. Compounds 32, 90, 100, 101, 108, 111, 112 were purified from the S. glabra which should impulse scientistc to perform more research on these compounds [40].

4. Conclusions

Because of the wide range of distribution, diverse structures and significant pharmacological activities of the CASEDs, more natural product researchers are paying great attention to these compounds. However, most studies on the CASED since 1977 are still isolated and report simple pharmacological activities. More in-depth research on the pharmacological mechanisms of action should be performed. Full exploitation on the broad array of biological activities of CASEDs awaits more researchers to devote themselves to this field.

Cpd.	R1	R2	R3	R4	R5	Cpd.	R1	R2	R3	R4	R5
1	E	H	H	H	G	6	R	H	H	E	H
2	G	H	H	H	G	7	S	H	H	H	G
3	S	H	H	H	I	8	S	H	H	G	H
4	I	H	H	H	I	9	T	H	H	H	G
5	R	H	H	H	E	10	V	H	H	H	G

Cpd.	R1	R2	R3	R4
11	H	H	H	F
12	H	A	F	H
13	H	A	F	F
14	H	F	A	H
15	H	A	F′	H

Cpd.	R1	R2	R3	R4	R5
16	H	H	H	H	E
17	H	H	H	H	G
18	H	H	H	H	K
19	H	H	H	E	H
20	H	H	G′	H	G

Cpd.	R1	R2	R3	R4	R5	R6	R7	R8	Cpd.	R1	R2	R3	R4	R5	R6	R7	R8
28	H	H	H	H	H	H	H	I	75	H	H	H	K	H	H	H	H
29	H	H	H	H	H	H	H	K	76	H	H	H	K	H	H	H	I
30.	H	H	H	H	H	H	H	M	77	H	H	H	M	H	H	H	M
31	H	H	H	H	H	E	H	E	78	H	H	H	M	H	H	H	H
32	H	H	H	H	H	I	H	I	79	H	H	A	A	H	I	H	I
33	H	H	H	H	H	I	H	E	80	H	H	A	B	H	H	H	M
34	H	H	H	H	K	H	H	I	81	H	H	A	I	H	H	H	I
35	H	H	H	H	K	H	H	K	82	H	H	A	K	H	H	H	K
36	H	H	H	H	A	H	H	I	83	H	H	B	H	H	H	H	I
37	H	H	H	H	E	E	H	E	84	H	H	B	H	H	H	H	M
38	H	H	H	H	E	I	H	E	85	H	H	E	A	H	I	H	I
39	H	H	H	H	E	I	H	I	86	H	H	I	H	H	I	H	I
40	H	H	H	H	E	I	A	I	87	H	H	I	A	H	I	H	I
41	H	H	H	H	I	I	H	E	88	H	H	K	H	H	H	H	K
42	H	H	H	H	I	I	H	I	89	H	A	H	A	A	H	H	E
43	H	H	H	A	H	H	H	M	90	H	A	H	A	H	I	H	I
44	H	H	H	A	H	H	H	I	91	H	A	H	I	E	E	H	E
45	H	H	H	A	H	I	H	I	92	H	A	H	I	H	A	H	I
46	H	H	H	A	E	I	H	E	93	H	A	H	I	H	A	A	I
47	H	H	H	A	E	I	H	I	94	H	A	H	K	H	H	H	K
48	H	H	H	B	H	H	H	I	95	H	I	H	H	H	I	H	H
49	H	H	H	B	H	H	H	M	96	H	A	A	A	A	H	H	E
50	H	H	H	B	H	H	H	K	97	A	H	H	A	A	I	H	I
51	H	H	H	C	H	H	H	M	98	A	H	H	A	H	I	H	I
52	H	H	H	C	H	H	H	K	99	A	H	H	A	I	I	H	E
53	H	H	H	D	H	H	H	H	100	A	H	H	A	I	I	H	I
54	H	H	H	E	H	H	H	K	101	A	H	H	A	E	I	H	I
55	H	H	H	E	H	H	H	M	102	A	H	H	I	E	E	H	E
56	H	H	H	E	H	H	I	I	103	A	H	H	I	I	E	H	E′
57	H	H	H	E	E	E	H	E	104	A	H	H	H	E	E	H	E
58	H	H	H	E	E	I	H	E	105	A	H	H	H	E	I	H	I
59	H	H	H	G	H	H	H	H	106	A	H	H	H	E	I	H	E
60	H	H	H	G	H	H	I	I	107	A	H	H	H	H	I	H	I
61	H	H	H	I	H	H	H	M	108	A	H	A	A	H	I	H	I
62	H	H	H	I	H	H	H	H	109	A	H	A	A	A	D	H	D
63	H	H	H	I	I	E	H	E	110	A	H	A	A	A	I	H	I
64	H	H	H	I	I	I	H	E	111	A	H	A	A	I	I	H	I
65	H	H	H	I	H	E	H	E	112	A	H	A	A	E	I	H	I
66	H	H	H	I	E	E	H	H	113	A	H	A	I	E	E	H	E
67	H	H	H	I	E	E	H	E	114	A	H	E	H	H	I	H	I
68	H	H	H	I	H	H	A	I	115	A	H	I	H	H	I	H	I
69	H	H	H	I	H	A	H	I	116	A	A	A	A	H	H	H	E
70	H	H	H	I	H	A	A	I	117	A	A	H	A	A	H	H	E
71	H	H	H	I	H	H	H	I	118	E	H	A	H	A	E	H	E
72	H	H	H	K	H	H	H	M	119	I	H	H	H	H	I	H	I
73	H	H	H	K	H	H	H	K	120	A	A	A	A	H	H	H	G
74	H	H	H	K	H	H	K	K

Cpd.	R1	R2	R3	R4
121	S	G	H	H

Cpd.	R1	R2	R3	R4	R5	R6	R7	Cpd.	R1	R2	R3	R4	R5	R6	R7
122	R	H	H	E	H	H	H	132	S	H	G′	H	H	H	H
123	R	H	E	H	H	H	H	133	S	H	I	H	H	H	H
124	G	H	T	H	H	H	H	134	S	H	I′	H	H	H	H
125	Q	H	G	H	H	H	H	135	S	A	G	H	H	H	A
126	R	H	E	H	H	H	H	136	S	A	G	H	H	H	H
127	S	H	H	E	H	H	H	137	T	H	A	I	H	A	H
128	S	H	H	G	H	H	H	138	T	H	I	H	H	H	H
129	S	H	E′	H	H	H	H	139	T	H	I′	H	H	H	H
130	S	H	G	D	H	H	H	140	U	H	I	H	H	H	H
131	S	H	G	H	H	H	H

Cpd.	R1	R2	R3	R4
141	S	H	G	H

Cpd.	R1	R2	R3	R4
142	S	H	H	G
143	S	H	G	H

Cpd.	R1	R2	R3	R4
144	S	H	G	H

Cpd.	R1	R2	R3	R4
145	H	H	H	E
146	H	H	G	H
147	T	H	H	I
148	S	H	H	G

Cpd.	R1	R2	R3	R4
148	S	H	H	G

Cpd.	R1	R2	R3
149	D	H	R

Cpd.	R1	R2
150	G	K
151	I	K
152	K	K
153	L	I
154	L	K
155	L	L

Cpd.	R1	R2	R3	Cpd.	R1	R2	R3
163	K	H	K	165	M	I	K
164	M	H	K	166	M	K	K

Cpd.	R1	R2	R3	R4	R5	R6	R7
167	H	H	I	H	H	H	K
168	H	H	K	H	H	H	K

Cpd.	R1	R2	Cpd.	R1	R2
169	I	H	171	H	I
170	K	H	172	H	K

Cpd.	R1	R2	R3	R4	R5	R6	R7	R8
173	H	H	H	O	H	H	A	I
174	H	H	P	B	H	H	H	B

Cpd.	R1	R2	R3
175	E	A	D

Cpd.	R1	R2	R3	R4
176	S	H	H	G
177	S	H	G	H

Cpd.	R1	R2
178	S	G

Cpd.	R1	R2
179	S	G
180	S	I
181	T	I
182	U	I

Cpd.	R1	R2	R3
183	S	H	G
184	S	G	H
185	S	G	A
186	S	I	H
187	T	I	H

Cpd.	R1	R2	R3
188	S	G	H
189	S	G	A
190	S	H	G
191	S	H	I
192	T	H	I

Cpd.	R1	R2	R3
193	S	G	A

Cpd.	R1	R2	R3
194	S	G	H
195	S	I	H

Cpd.	R1	R2	R3
196	U	H	I

Cpd.	R1	R2	R3
197	S	H	G
198	S	H	I
199	S	H	I′
200	S	H	I
201	T	H	I

Cpd.	R1	R2	R3
202	S	H	G
203	U	H	G
204	U	H	I
205	U	H	I′

Cpd.	R1	R2	R3
206	S	H	G
207	S	H	I

Cpd.	R1	R2	R3
208	S	H	E
209	S	H	G
210	S	H	I
211	S	H	I′
212	U	H	I
213	U	H	I′

Cpd.	R1	R2	R3
214	S	H	G
215	U	H	G
216	U	H	I

Cpd.	R1	R2	R3
217	S	H	G
218	S	A	G

Cpd.	R1	R2	R3
219	S	H	G

Cpd.	R1	R2	R3	R4
220	S	H	G	H

Cpd.	R1	R2	R3	R4
221	E	H	I	H
222	S	H	G	H
223	S	A	G	H

Cpd.	R1	R2	R3	R4
224	H	H	I	H

Cpd.	R1	R2	R3	R4
225	S	H	G	H
226	S	H	I	H
227	T	H	I	H

Cpd.	R1	R2	R3	R4
228	S	H	G	H

Cpd.	R1	R2	R3	R4
229	S	H	G	H

Cpd.	R1	R2	R3	R4
230	S	H	G	H

Cpd.	R1	R2	R3	R4
231	S	H	G	H
232	S	H	I	H

Cpd.	R1	R2	R3	R4
233	R	H	H	E
234	R	H	H	G

Cpd.	R1	R2	R3	R4
235	H	H	G	H
236	R	H	E	H
237	R	H	G	H
238	S	H	G	H

Cpd.	R1	R2	R3	R4
239	S	H	G	H
240	S	H	I	H

Cpd.	R1	R2	R3	R4
241	S	H	G	H
242	T	H	I	H

Cpd.	R1	R2	R3
243	S	G	H

Cpd.	R1	R2	R3
244	S	G	H

Cpd.	R1	R2	R3
245	T	H	I

Cpd.	R1	R2	R3
246	S	G	H

Cpd.	R1	R2	Cpd.	R1	R2
249	D	R	252	F	R
250	E	R	253	I	R
251	E′	R	254	J	R

Cpd.	R1	R2	R3	R4	Cpd.	R1	R2	R3	R3
255	K	H	H	K	258	K	K	H	K
256	K	E	H	K	259	M	I	H	K
257	K	I	H	K	260	M	K	H	K

Cpd.	R1	R2	R3	R4	R5	R6
261	I	B	H	I	A	A

Cpd.	R1	R2	R3	R4	R5	Cpd.	R1	R2	R3	R4	R5
262	E	B	I	A	A	269	E	B	I	H	I
263	E	B	H	E	A	270	E	B	I	A	I
264	E	B	E	H	A	271	I	B	E	A	A
265	E	B	E	A	A	272	I	B	I	H	A
266	E	B	E	A	E	273	I	B	I	A	H
267	E	B	I	H	A	274	I	B	I	A	A
268	E	B	I	H	E

Cpd.	R1	R2	R3
275	J	H	H

Cpd.	R1	R2	R3
276	S	G	H

Cpd.	R1	R2	R3	R4	R5	R6	Cpd.	R1	R2	R3	R4	R5	R6
280	E	B	E	H	H	A	288	E	B	I	A	A	A
281	E	B	E	H	A	A	289	I	B	I	H	H	A
282	E	B	E	A	H	A	290	I	B	I	H	A	A
283	E	B	E	A	A	A	291	I	B	I	A	H	A
284	E	B	I	H	H	A	292	I	B	I	A	A	A
285	E	B	I	H	A	A	293	I	B	E′	A	H	A
286	E	B	I	A	H	A	294	I	B	H	I	H	A
287	E	B	I	A	H	H

Cpd.	R1	R2	R3	R4	R5	Cpd.	R1	R2	R3	R4	R5
295	E	B	I	A	H	301	I	B	I	H	H
296	E	B	I	A	A	302	I	B	I	H	A
297	E	B	I′	A	A	303	I	B	I	A	H
298	E′	B	I	A	A	304	I	B	I	A	A
299	I	B	E	A	H	305	I	B	I′	A	A
300	I	B	E	A	A

Cpd.	R1	R2	R3	R4	R5
306	E	B	N	A	H
307	E	B	N	A	A
308	E	B	P	A	H
309	E	B	P	A	E
310	E	B	P	A	I
311	I	B	N	A	H
312	I	B	P	H	I
313	I	B	P	A	H
314	I	B	P	A	A
315	I	B	P	A	E
316	I	B	P	A	I

Cpd.	R1	R2	R3
317	F	H	H
318	F′	H	H
319	J	H	H
320	J′	H	H

Cpd.	R1	R2	R3	R4	R5
321	E	B	A	H	A
322	E	B	A	A	A

Cpd.	R1	R2	R3	R4	R5
323	E	B	A	H	A
324	E	B	A	A	A

Cpd.	R1	R2	R3	R4
325	J	H	H	H
326	J	A	H	H
327	J′	A	H	H
328	F	H	H	H

Cpd.	R1	R2	R3	R4
329	F	H	H	H

Cpd.	R1	R2	R3
330	M	H	H

Cpd.	R1	R2
331	F	H
332	F′	H

Cpd.	R1	R2	R3	R4	R5
333	E	B	A	A	A

Cpd.	R1	R2
334	F	H