7β-Hydroxy-artemisinin.

CRYSTALS OF THE TITLE COMPOUND [SYSTEMATIC NAME: (3R,6R,7S,8aR,9R,12aR)-7-hydr-oxy-3,6,9-trimethyl-octa-hydro-3,12-ep-oxy[1,2]dioxepino[4,3-i]isochromen-10(3H)-one], C(15)H(22)O(6), were obtained from microbial transformation of artemisinin by a culture of Cunninghamella elegans. The stereochemistry of the compound is consistent with the spectroscopic findings in previously published works. A weak O-H⋯O hydrogen bond occurs in the crystal structure, together with intermolecular C-H⋯O hydrogen bonds.

Related literature

For related literature, see: Blasko & Cordell (1988 ▶); Chen & Yu (2001 ▶); Liu et al. (2006 ▶); Parshikov et al. (2004 ▶, 2005 ▶, 2006 ▶); Zhan, Zhang et al. (2002 ▶); CDC (2007 ▶); Klayman (1985 ▶); TDR (2007 ▶); Zhan, Guo et al. (2002 ▶).

Experimental

Crystal data

C15H22O6

M = 298.33

Orthorhombic,

a = 6.3047 (2) Å

b = 9.1266 (2) Å

c = 24.5309 (6) Å

V = 1411.52 (6) Å3

Z = 4

Cu Kα radiation

μ = 0.90 mm−1

T = 296 (2) K

0.23 × 0.15 × 0.12 mm

Data collection

Bruker SMART CCD diffractometer

Absorption correction: none

12572 measured reflections

2464 independent reflections

2456 reflections with I > 2σ(I)

R int = 0.020

Refinement

R[F 2 > 2σ(F 2)] = 0.028

wR(F 2) = 0.072

S = 1.08

2464 reflections

194 parameters

H-atom parameters constrained

Δρmax = 0.24 e Å−3

Δρmin = −0.16 e Å−3

Absolute structure: Flack (1983 ▶), with 990 Friedel pairs

Flack parameter: 0.11 (14)

Data collection: SMART (Bruker, 2002 ▶); cell refinement: SAINT (Bruker, 2002 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Bruker, 2002 ▶); software used to prepare material for publication: SHELXTL.

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808000251/hb2682sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808000251/hb2682Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C15H22O6	F000 = 640
Mr = 298.33	Dx = 1.404 Mg m−3
Orthorhombic, P212121	Cu Kα radiation λ = 1.54178 Å
Hall symbol: P 2ac 2ab	Cell parameters from 9907 reflections
a = 6.3047 (2) Å	θ = 3.6–66.0º
b = 9.1266 (2) Å	µ = 0.90 mm−1
c = 24.5309 (6) Å	T = 296 (2) K
V = 1411.52 (6) Å3	Needle, colourless
Z = 4	0.23 × 0.15 × 0.12 mm

Bruker SMART CCD diffractometer	2456 reflections with I > 2σ(I)
Monochromator: graphite	Rint = 0.020
T = 100 K	θmax = 66.5º
ω scans	θmin = 3.6º
Absorption correction: none	h = −7→7
12572 measured reflections	k = −10→10
2464 independent reflections	l = −28→29

Refinement on F2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F2 > 2σ(F2)] = 0.028	w = 1/[σ2(Fo2) + (0.0408P)2 + 0.3857P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.072	(Δ/σ)max = 0.001
S = 1.08	Δρmax = 0.24 e Å−3
2464 reflections	Δρmin = −0.16 e Å−3
194 parameters	Extinction correction: none
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983), 990 Friedel pairs
Secondary atom site location: difference Fourier map	Flack parameter: 0.11 (14)

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes)are estimated using the full covariance matrix. The cell e.s.d.'s are takeninto account individually in the estimation of e.s.d.'s in distances, anglesand torsion angles; correlations between e.s.d.'s in cell parameters are onlyused when they are defined by crystal symmetry. An approximate (isotropic)treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR andgoodness of fit S are based on F2, conventional R-factors R are basedon F, with F set to zero for negative F2. The threshold expression ofF2 > σ(F2) is used only for calculating R-factors(gt) etc. and isnot relevant to the choice of reflections for refinement. R-factors basedon F2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

	x	y	z	Uiso*/Ueq
O1	0.61177 (15)	1.07519 (10)	0.80390 (4)	0.0180 (2)
O2	0.80303 (16)	1.07108 (10)	0.76947 (4)	0.0196 (2)
O5	1.06564 (17)	1.28606 (12)	0.91615 (4)	0.0257 (2)
O11	1.00751 (15)	1.07562 (11)	0.87615 (4)	0.0202 (2)
O3	0.96938 (15)	0.88540 (11)	0.81679 (4)	0.0179 (2)
O4	0.3981 (2)	0.79291 (13)	0.99868 (4)	0.0312 (3)
H4	0.5183	0.7748	1.0095	0.047*
C10	0.9351 (2)	1.20070 (15)	0.90000 (5)	0.0180 (3)
C8A	0.5644 (2)	1.08876 (15)	0.89973 (5)	0.0164 (3)
H8A	0.4185	1.1175	0.8910	0.020*
C15	0.6384 (2)	1.33349 (16)	0.94762 (6)	0.0231 (3)
H15A	0.6812	1.2917	0.9818	0.035*
H15B	0.4877	1.3486	0.9477	0.035*
H15C	0.7091	1.4256	0.9424	0.035*
C6	0.4729 (2)	0.76793 (15)	0.90164 (6)	0.0196 (3)
H6	0.6086	0.7227	0.9114	0.024*
C7	0.4095 (2)	0.87131 (16)	0.94816 (6)	0.0211 (3)
H7	0.2672	0.9086	0.9401	0.025*
C3	0.8719 (2)	0.92375 (15)	0.76551 (5)	0.0189 (3)
C13	1.0455 (3)	0.92467 (16)	0.72317 (6)	0.0244 (3)
H13A	0.9850	0.9423	0.6879	0.037*
H13B	1.1165	0.8316	0.7232	0.037*
H13C	1.1456	1.0007	0.7315	0.037*
C5	0.5912 (2)	0.74642 (15)	0.80360 (6)	0.0205 (3)
H5A	0.6983	0.6846	0.8203	0.025*
H5B	0.4763	0.6831	0.7919	0.025*
C9	0.6978 (2)	1.22918 (15)	0.90130 (6)	0.0177 (3)
H9	0.6651	1.2817	0.8675	0.021*
C14	0.3095 (2)	0.64461 (16)	0.89482 (6)	0.0241 (3)
H14A	0.2810	0.6009	0.9296	0.036*
H14B	0.3647	0.5716	0.8705	0.036*
H14C	0.1806	0.6842	0.8801	0.036*
C4	0.6880 (2)	0.81822 (16)	0.75307 (6)	0.0207 (3)
H4A	0.5777	0.8717	0.7340	0.025*
H4B	0.7389	0.7419	0.7289	0.025*
C12A	0.6419 (2)	0.98999 (15)	0.85346 (6)	0.0164 (3)
C12	0.8748 (2)	0.95112 (15)	0.86157 (6)	0.0166 (3)
H12	0.8821	0.8810	0.8918	0.020*
C8	0.5571 (2)	1.00298 (15)	0.95338 (5)	0.0185 (3)
H8B	0.6987	0.9698	0.9627	0.022*
H8C	0.5074	1.0665	0.9824	0.022*
C5A	0.5049 (2)	0.85116 (16)	0.84744 (5)	0.0171 (3)
H5A1	0.3644	0.8832	0.8352	0.021*

	U11	U22	U33	U12	U13	U23
O1	0.0161 (5)	0.0194 (5)	0.0185 (5)	0.0033 (4)	0.0003 (4)	0.0022 (4)
O2	0.0198 (5)	0.0179 (5)	0.0212 (5)	0.0016 (4)	0.0043 (4)	0.0019 (4)
O5	0.0209 (5)	0.0243 (5)	0.0318 (5)	−0.0053 (5)	−0.0020 (4)	−0.0077 (4)
O11	0.0135 (5)	0.0206 (5)	0.0266 (5)	−0.0006 (4)	−0.0026 (4)	−0.0048 (4)
O3	0.0156 (4)	0.0185 (5)	0.0196 (5)	0.0031 (4)	−0.0004 (4)	−0.0017 (4)
O4	0.0419 (7)	0.0276 (6)	0.0240 (5)	−0.0063 (5)	0.0054 (5)	0.0044 (5)
C10	0.0188 (7)	0.0186 (7)	0.0166 (6)	−0.0016 (6)	−0.0004 (5)	−0.0003 (5)
C8A	0.0130 (6)	0.0155 (6)	0.0208 (6)	0.0007 (6)	−0.0018 (5)	−0.0004 (5)
C15	0.0225 (7)	0.0183 (7)	0.0283 (7)	−0.0007 (6)	0.0008 (6)	−0.0034 (6)
C6	0.0174 (7)	0.0171 (7)	0.0244 (7)	−0.0005 (6)	−0.0004 (6)	0.0021 (6)
C7	0.0194 (7)	0.0214 (7)	0.0225 (7)	−0.0011 (6)	0.0033 (6)	0.0025 (6)
C3	0.0213 (7)	0.0165 (7)	0.0189 (6)	0.0020 (6)	−0.0004 (6)	−0.0002 (5)
C13	0.0279 (8)	0.0201 (7)	0.0253 (7)	0.0001 (6)	0.0054 (6)	−0.0001 (6)
C5	0.0205 (7)	0.0174 (6)	0.0234 (7)	−0.0033 (6)	−0.0011 (6)	−0.0029 (6)
C9	0.0178 (7)	0.0160 (7)	0.0192 (6)	0.0006 (6)	−0.0018 (5)	0.0000 (5)
C14	0.0235 (7)	0.0193 (7)	0.0295 (8)	−0.0029 (7)	0.0009 (6)	0.0020 (6)
C4	0.0226 (7)	0.0200 (7)	0.0196 (6)	0.0004 (6)	−0.0024 (6)	−0.0023 (5)
C12A	0.0157 (7)	0.0159 (6)	0.0175 (6)	0.0009 (6)	−0.0024 (5)	0.0018 (5)
C12	0.0146 (6)	0.0154 (6)	0.0198 (7)	−0.0007 (5)	−0.0002 (5)	0.0003 (5)
C8	0.0189 (7)	0.0184 (7)	0.0181 (6)	0.0012 (6)	0.0009 (6)	−0.0014 (5)
C5A	0.0126 (6)	0.0186 (7)	0.0202 (6)	−0.0006 (5)	−0.0027 (5)	−0.0004 (5)

O1—C12A	1.4556 (16)	C7—C8	1.525 (2)
O1—O2	1.4727 (13)	C7—H7	0.9800
O2—C3	1.4164 (17)	C3—C13	1.509 (2)
O5—C10	1.2003 (18)	C3—C4	1.538 (2)
O11—C10	1.3615 (17)	C13—H13A	0.9600
O11—C12	1.4558 (17)	C13—H13B	0.9600
O3—C12	1.3866 (17)	C13—H13C	0.9600
O3—C3	1.4429 (16)	C5—C4	1.529 (2)
O4—C7	1.4328 (17)	C5—C5A	1.5383 (19)
O4—H4	0.8200	C5—H5A	0.9700
C10—C9	1.5193 (19)	C5—H5B	0.9700
C8A—C12A	1.5297 (18)	C9—H9	0.9800
C8A—C8	1.5320 (18)	C14—H14A	0.9600
C8A—C9	1.5333 (19)	C14—H14B	0.9600
C8A—H8A	0.9800	C14—H14C	0.9600
C15—C9	1.5289 (19)	C4—H4A	0.9700
C15—H15A	0.9600	C4—H4B	0.9700
C15—H15B	0.9600	C12A—C12	1.5234 (19)
C15—H15C	0.9600	C12A—C5A	1.5405 (19)
C6—C7	1.5336 (19)	C12—H12	0.9800
C6—C14	1.535 (2)	C8—H8B	0.9700
C6—C5A	1.5444 (18)	C8—H8C	0.9700
C6—H6	0.9800	C5A—H5A1	0.9800
C12A—O1—O2	111.00 (9)	C5A—C5—H5A	108.2
C3—O2—O1	108.33 (9)	C4—C5—H5B	108.2
C10—O11—C12	124.56 (11)	C5A—C5—H5B	108.2
C12—O3—C3	113.74 (10)	H5A—C5—H5B	107.4
C7—O4—H4	109.5	C10—C9—C15	111.29 (12)
O5—C10—O11	117.15 (13)	C10—C9—C8A	113.38 (11)
O5—C10—C9	123.87 (13)	C15—C9—C8A	113.89 (11)
O11—C10—C9	118.85 (12)	C10—C9—H9	105.8
C12A—C8A—C8	110.23 (11)	C15—C9—H9	105.8
C12A—C8A—C9	109.62 (11)	C8A—C9—H9	105.8
C8—C8A—C9	114.95 (11)	C6—C14—H14A	109.5
C12A—C8A—H8A	107.2	C6—C14—H14B	109.5
C8—C8A—H8A	107.2	H14A—C14—H14B	109.5
C9—C8A—H8A	107.2	C6—C14—H14C	109.5
C9—C15—H15A	109.5	H14A—C14—H14C	109.5
C9—C15—H15B	109.5	H14B—C14—H14C	109.5
H15A—C15—H15B	109.5	C5—C4—C3	114.09 (11)
C9—C15—H15C	109.5	C5—C4—H4A	108.7
H15A—C15—H15C	109.5	C3—C4—H4A	108.7
H15B—C15—H15C	109.5	C5—C4—H4B	108.7
C7—C6—C14	110.94 (12)	C3—C4—H4B	108.7
C7—C6—C5A	111.84 (11)	H4A—C4—H4B	107.6
C14—C6—C5A	110.77 (11)	O1—C12A—C12	111.07 (11)
C7—C6—H6	107.7	O1—C12A—C8A	105.26 (10)
C14—C6—H6	107.7	C12—C12A—C8A	110.38 (11)
C5A—C6—H6	107.7	O1—C12A—C5A	106.63 (10)
O4—C7—C8	110.58 (12)	C12—C12A—C5A	111.18 (11)
O4—C7—C6	110.46 (12)	C8A—C12A—C5A	112.12 (11)
C8—C7—C6	112.84 (12)	O3—C12—O11	106.56 (11)
O4—C7—H7	107.6	O3—C12—C12A	114.31 (11)
C8—C7—H7	107.6	O11—C12—C12A	113.85 (11)
C6—C7—H7	107.6	O3—C12—H12	107.2
O2—C3—O3	107.52 (10)	O11—C12—H12	107.2
O2—C3—C13	105.32 (11)	C12A—C12—H12	107.2
O3—C3—C13	107.01 (11)	C7—C8—C8A	110.41 (11)
O2—C3—C4	112.14 (12)	C7—C8—H8B	109.6
O3—C3—C4	110.01 (11)	C8A—C8—H8B	109.6
C13—C3—C4	114.44 (12)	C7—C8—H8C	109.6
C3—C13—H13A	109.5	C8A—C8—H8C	109.6
C3—C13—H13B	109.5	H8B—C8—H8C	108.1
H13A—C13—H13B	109.5	C5—C5A—C12A	112.32 (11)
C3—C13—H13C	109.5	C5—C5A—C6	110.02 (11)
H13A—C13—H13C	109.5	C12A—C5A—C6	113.30 (11)
H13B—C13—H13C	109.5	C5—C5A—H5A1	106.9
C4—C5—C5A	116.20 (12)	C12A—C5A—H5A1	106.9
C4—C5—H5A	108.2	C6—C5A—H5A1	106.9

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4···O4i	0.82	2.48	3.2488 (18)	156
C5A—H5A1···O3ii	0.98	2.53	3.4731 (16)	161
C5—H5B···O2iii	0.97	2.53	3.4571 (17)	159
C13—H13B···O2iv	0.96	2.44	3.3703 (18)	164

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O4—H4⋯O4i	0.82	2.48	3.2488 (18)	156
C5A—H5A1⋯O3ii	0.98	2.53	3.4731 (16)	161
C5—H5B⋯O2iii	0.97	2.53	3.4571 (17)	159
C13—H13B⋯O2iv	0.96	2.44	3.3703 (18)	164

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) .