Absolute configuration of fibaruretin B.

The title furan-oditerpenoid, known as fibaruretin B (systematic name: 2β,3α-dihy-droxy-2,3,7,8α-tetra-hydro-penianthic acid lactone), C(20)H(24)O(7), was isolated from the roots of Arcangelisia flava. The absolute configurations at positions 2, 3, 4, 4a, 7, 9, 10a and 10b of fibaruretin B are S, R, S, R, S, S, S and S, respectively. In the crystal structure, the mol-ecules are linked into infinite chains along the c axis by O-H⋯O hydrogen bonds and weak C-H⋯O inter-actions.

Related literature

For ring conformations, see: Cremer & Pople (1975 ▶). For bond-length data, see: Allen et al. (1987 ▶). For background to and activities of furan­oditerpenoids, see: Ito & Furukawa (1969 ▶); Keawpradub et al. (2005 ▶); Moody et al. (2006 ▶); Nguyen-Pouplin et al. (2007 ▶); Su et al. (2008 ▶). For a related structure, see: Bakhari et al. (1998 ▶). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986 ▶).

Experimental

Crystal data

C20H24O7

M = 376.39

Monoclinic,

a = 7.0942 (2) Å

b = 11.7149 (4) Å

c = 10.1921 (3) Å

β = 90.805 (1)°

V = 846.96 (5) Å3

Z = 2

Cu Kα radiation

μ = 0.93 mm−1

T = 100 K

0.43 × 0.12 × 0.08 mm

Data collection

Bruker APEX DUO CCD area-detector diffractometer

Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T min = 0.692, T max = 0.926

11247 measured reflections

2645 independent reflections

2641 reflections with I > 2σ(I)

R int = 0.018

Refinement

R[F 2 > 2σ(F 2)] = 0.025

wR(F 2) = 0.066

S = 1.09

2645 reflections

254 parameters

1 restraint

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.19 e Å−3

Δρmin = −0.15 e Å−3

Absolute structure: Flack (1983 ▶), with 1098 Friedel pairs

Flack parameter: 0.03 (12)

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ▶).

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811014887/is2703sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811014887/is2703Isup2.hkl

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

C20H24O7	F(000) = 400
Mr = 376.39	Dx = 1.476 Mg m−3
Monoclinic, P21	Melting point = 539–540 K
Hall symbol: P 2yb	Cu Kα radiation, λ = 1.54178 Å
a = 7.0942 (2) Å	Cell parameters from 2645 reflections
b = 11.7149 (4) Å	θ = 4.3–66.5°
c = 10.1921 (3) Å	µ = 0.93 mm−1
β = 90.805 (1)°	T = 100 K
V = 846.96 (5) Å3	Needle, colourless
Z = 2	0.43 × 0.12 × 0.08 mm

Bruker APEX DUO CCD area-detector diffractometer	2645 independent reflections
Radiation source: sealed tube	2641 reflections with I > 2σ(I)
graphite	Rint = 0.018
φ and ω scans	θmax = 66.5°, θmin = 4.3°
Absorption correction: multi-scan (SADABS; Bruker, 2009)	h = −8→8
Tmin = 0.692, Tmax = 0.926	k = −11→13
11247 measured reflections	l = −11→12

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.025	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.066	w = 1/[σ2(Fo2) + (0.0393P)2 + 0.1838P] where P = (Fo2 + 2Fc2)/3
S = 1.09	(Δ/σ)max = 0.001
2645 reflections	Δρmax = 0.19 e Å−3
254 parameters	Δρmin = −0.15 e Å−3
1 restraint	Absolute structure: Flack (1983), with 1098 Friedel pairs
Primary atom site location: structure-invariant direct methods	Flack parameter: 0.03 (12)

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K.

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

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on 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	0.09153 (14)	1.02466 (10)	0.68755 (10)	0.0211 (2)
O2	0.32424 (17)	1.15137 (10)	0.70124 (12)	0.0296 (3)
O3	0.27902 (16)	0.75672 (11)	0.80552 (11)	0.0252 (3)
H1O3	0.255 (4)	0.732 (2)	0.883 (3)	0.061 (8)*
O4	0.55436 (14)	0.96856 (12)	0.80516 (10)	0.0239 (3)
H1O4	0.527 (3)	0.965 (2)	0.888 (3)	0.046 (6)*
O5	0.31561 (13)	0.83615 (10)	0.09804 (9)	0.0178 (2)
O6	0.53283 (13)	0.96975 (11)	0.09604 (9)	0.0206 (2)
O7	−0.09239 (17)	0.58024 (10)	−0.04095 (11)	0.0275 (3)
C1	0.08225 (19)	0.83863 (15)	0.58193 (13)	0.0188 (3)
H1A	−0.0153	0.8680	0.5235	0.023*
H1B	0.0542	0.7589	0.5981	0.023*
C2	0.07216 (19)	0.90202 (14)	0.70997 (14)	0.0185 (3)
H2A	−0.0459	0.8851	0.7547	0.022*
C3	0.2412 (2)	0.87467 (14)	0.79792 (13)	0.0181 (3)
H3A	0.2207	0.9052	0.8861	0.022*
C4	0.39121 (19)	0.94530 (14)	0.72888 (14)	0.0170 (3)
C5	0.45100 (19)	0.89413 (13)	0.59309 (13)	0.0147 (3)
C6	0.56241 (19)	0.98757 (13)	0.51939 (14)	0.0162 (3)
H6A	0.4927	1.0586	0.5247	0.019*
H6B	0.6821	0.9989	0.5647	0.019*
C7	0.60174 (18)	0.96286 (14)	0.37404 (14)	0.0163 (3)
H7A	0.6105	1.0347	0.3272	0.020*
H7B	0.7225	0.9246	0.3676	0.020*
C8	0.44977 (18)	0.88869 (13)	0.30780 (13)	0.0145 (3)
H8A	0.4901	0.8096	0.3218	0.017*
C9	0.25169 (18)	0.89794 (14)	0.37078 (13)	0.0151 (3)
C10	0.27476 (18)	0.84594 (14)	0.51044 (13)	0.0147 (3)
H10A	0.3078	0.7660	0.4940	0.018*
C11	0.1130 (2)	0.82256 (15)	0.28832 (13)	0.0200 (3)
H11A	0.0532	0.7684	0.3465	0.024*
H11B	0.0149	0.8712	0.2516	0.024*
C12	0.20406 (19)	0.75715 (14)	0.17735 (13)	0.0158 (3)
H12A	0.2855	0.6969	0.2132	0.019*
C13	0.0605 (2)	0.70654 (14)	0.08547 (14)	0.0169 (3)
C14	−0.1096 (2)	0.75809 (15)	0.03551 (14)	0.0214 (3)
H14A	−0.1519	0.8318	0.0517	0.026*
C15	−0.1952 (2)	0.67891 (16)	−0.03912 (14)	0.0245 (4)
H15A	−0.3091	0.6896	−0.0837	0.029*
C16	0.0642 (2)	0.60018 (15)	0.03548 (15)	0.0226 (3)
H16A	0.1600	0.5475	0.0508	0.027*
C17	0.43951 (19)	0.90427 (14)	0.16102 (14)	0.0161 (3)
C18	0.2742 (2)	1.05332 (15)	0.70502 (14)	0.0196 (3)
C19	0.5852 (2)	0.79280 (14)	0.61724 (14)	0.0185 (3)
H19A	0.6860	0.8160	0.6751	0.028*
H19B	0.6363	0.7681	0.5353	0.028*
H19C	0.5170	0.7311	0.6564	0.028*
C20	0.17620 (19)	1.02044 (14)	0.36919 (14)	0.0185 (3)
H20A	0.0509	1.0215	0.4036	0.028*
H20B	0.1736	1.0485	0.2807	0.028*
H20C	0.2567	1.0681	0.4223	0.028*

	U11	U22	U33	U12	U13	U23
O1	0.0209 (5)	0.0249 (7)	0.0177 (5)	0.0024 (4)	0.0029 (4)	−0.0014 (5)
O2	0.0385 (6)	0.0192 (7)	0.0313 (6)	−0.0040 (5)	0.0147 (5)	−0.0054 (5)
O3	0.0353 (6)	0.0215 (6)	0.0189 (6)	−0.0015 (5)	0.0068 (5)	0.0065 (5)
O4	0.0183 (5)	0.0407 (7)	0.0125 (5)	−0.0077 (5)	−0.0016 (4)	−0.0034 (5)
O5	0.0203 (5)	0.0222 (6)	0.0109 (4)	−0.0035 (4)	0.0008 (4)	−0.0001 (4)
O6	0.0215 (5)	0.0262 (6)	0.0143 (5)	−0.0042 (5)	0.0021 (4)	0.0028 (4)
O7	0.0346 (6)	0.0253 (7)	0.0225 (6)	−0.0079 (5)	−0.0056 (4)	−0.0038 (5)
C1	0.0175 (7)	0.0248 (9)	0.0141 (6)	−0.0075 (6)	0.0010 (5)	−0.0010 (6)
C2	0.0169 (7)	0.0244 (9)	0.0145 (7)	−0.0046 (6)	0.0041 (5)	0.0001 (6)
C3	0.0209 (7)	0.0223 (9)	0.0112 (7)	−0.0035 (6)	0.0025 (5)	−0.0010 (6)
C4	0.0162 (6)	0.0217 (9)	0.0131 (6)	−0.0044 (6)	−0.0011 (5)	−0.0020 (6)
C5	0.0147 (6)	0.0171 (8)	0.0124 (6)	−0.0016 (6)	0.0005 (5)	−0.0007 (6)
C6	0.0148 (6)	0.0187 (8)	0.0152 (7)	−0.0021 (6)	−0.0003 (5)	−0.0005 (6)
C7	0.0140 (6)	0.0205 (8)	0.0144 (7)	−0.0022 (6)	0.0016 (5)	0.0005 (6)
C8	0.0143 (6)	0.0155 (8)	0.0138 (7)	0.0006 (5)	0.0007 (5)	0.0001 (6)
C9	0.0142 (6)	0.0189 (8)	0.0122 (6)	−0.0022 (6)	0.0012 (5)	−0.0010 (6)
C10	0.0153 (6)	0.0158 (8)	0.0130 (7)	−0.0029 (5)	0.0010 (5)	−0.0015 (5)
C11	0.0159 (6)	0.0296 (9)	0.0144 (7)	−0.0044 (6)	0.0011 (5)	−0.0045 (6)
C12	0.0170 (6)	0.0171 (8)	0.0132 (6)	−0.0010 (6)	0.0001 (5)	0.0029 (6)
C13	0.0197 (7)	0.0185 (8)	0.0124 (6)	−0.0032 (6)	0.0022 (5)	0.0012 (6)
C14	0.0226 (7)	0.0249 (9)	0.0167 (7)	−0.0005 (6)	−0.0008 (5)	0.0000 (6)
C15	0.0248 (7)	0.0310 (10)	0.0177 (7)	−0.0055 (7)	−0.0041 (6)	0.0004 (6)
C16	0.0280 (8)	0.0209 (9)	0.0190 (7)	−0.0036 (6)	−0.0008 (6)	−0.0012 (6)
C17	0.0146 (6)	0.0178 (8)	0.0158 (7)	0.0040 (6)	0.0010 (5)	−0.0013 (6)
C18	0.0254 (7)	0.0210 (9)	0.0125 (6)	−0.0025 (6)	0.0070 (5)	−0.0040 (6)
C19	0.0166 (6)	0.0218 (9)	0.0172 (6)	0.0012 (6)	0.0005 (5)	0.0035 (6)
C20	0.0171 (6)	0.0232 (9)	0.0152 (7)	0.0032 (6)	−0.0005 (5)	0.0016 (6)

O1—C18	1.3482 (19)	C7—C8	1.5338 (19)
O1—C2	1.462 (2)	C7—H7A	0.9700
O2—C18	1.203 (2)	C7—H7B	0.9700
O3—C3	1.409 (2)	C8—C17	1.5078 (19)
O3—H1O3	0.86 (3)	C8—C9	1.5568 (17)
O4—C4	1.4117 (16)	C8—H8A	0.9800
O4—H1O4	0.87 (3)	C9—C20	1.532 (2)
O5—C17	1.3437 (18)	C9—C10	1.5548 (19)
O5—C12	1.4677 (17)	C9—C11	1.5593 (19)
O6—C17	1.2156 (19)	C10—H10A	0.9800
O7—C15	1.367 (2)	C11—C12	1.518 (2)
O7—C16	1.3677 (18)	C11—H11A	0.9700
C1—C2	1.504 (2)	C11—H11B	0.9700
C1—C10	1.5593 (18)	C12—C13	1.4962 (19)
C1—H1A	0.9700	C12—H12A	0.9800
C1—H1B	0.9700	C13—C16	1.347 (2)
C2—C3	1.521 (2)	C13—C14	1.436 (2)
C2—H2A	0.9800	C14—C15	1.340 (2)
C3—C4	1.528 (2)	C14—H14A	0.9300
C3—H3A	0.9800	C15—H15A	0.9300
C4—C18	1.531 (2)	C16—H16A	0.9300
C4—C5	1.5720 (18)	C19—H19A	0.9600
C5—C19	1.539 (2)	C19—H19B	0.9600
C5—C6	1.550 (2)	C19—H19C	0.9600
C5—C10	1.6006 (18)	C20—H20A	0.9600
C6—C7	1.5388 (19)	C20—H20B	0.9600
C6—H6A	0.9700	C20—H20C	0.9600
C6—H6B	0.9700
C18—O1—C2	108.45 (12)	C20—C9—C8	112.23 (12)
C3—O3—H1O3	109.8 (19)	C10—C9—C8	105.44 (11)
C4—O4—H1O4	109.2 (15)	C20—C9—C11	107.87 (11)
C17—O5—C12	117.74 (10)	C10—C9—C11	109.21 (12)
C15—O7—C16	106.07 (12)	C8—C9—C11	107.75 (11)
C2—C1—C10	115.53 (12)	C9—C10—C1	111.57 (11)
C2—C1—H1A	108.4	C9—C10—C5	114.52 (11)
C10—C1—H1A	108.4	C1—C10—C5	117.14 (11)
C2—C1—H1B	108.4	C9—C10—H10A	103.9
C10—C1—H1B	108.4	C1—C10—H10A	103.9
H1A—C1—H1B	107.5	C5—C10—H10A	103.9
O1—C2—C1	110.12 (12)	C12—C11—C9	114.55 (11)
O1—C2—C3	102.95 (12)	C12—C11—H11A	108.6
C1—C2—C3	111.13 (12)	C9—C11—H11A	108.6
O1—C2—H2A	110.8	C12—C11—H11B	108.6
C1—C2—H2A	110.8	C9—C11—H11B	108.6
C3—C2—H2A	110.8	H11A—C11—H11B	107.6
O3—C3—C2	112.76 (13)	O5—C12—C13	105.82 (10)
O3—C3—C4	115.02 (13)	O5—C12—C11	109.30 (12)
C2—C3—C4	99.38 (11)	C13—C12—C11	111.92 (11)
O3—C3—H3A	109.7	O5—C12—H12A	109.9
C2—C3—H3A	109.7	C13—C12—H12A	109.9
C4—C3—H3A	109.7	C11—C12—H12A	109.9
O4—C4—C3	114.97 (12)	C16—C13—C14	105.98 (13)
O4—C4—C18	111.49 (13)	C16—C13—C12	125.95 (15)
C3—C4—C18	98.12 (11)	C14—C13—C12	128.05 (15)
O4—C4—C5	109.22 (11)	C15—C14—C13	106.37 (16)
C3—C4—C5	113.41 (12)	C15—C14—H14A	126.8
C18—C4—C5	109.13 (12)	C13—C14—H14A	126.8
C19—C5—C6	107.67 (11)	C14—C15—O7	110.84 (14)
C19—C5—C4	109.10 (11)	C14—C15—H15A	124.6
C6—C5—C4	107.64 (12)	O7—C15—H15A	124.6
C19—C5—C10	106.79 (12)	C13—C16—O7	110.72 (14)
C6—C5—C10	113.19 (11)	C13—C16—H16A	124.6
C4—C5—C10	112.30 (10)	O7—C16—H16A	124.6
C7—C6—C5	115.73 (12)	O6—C17—O5	118.17 (13)
C7—C6—H6A	108.3	O6—C17—C8	126.71 (13)
C5—C6—H6A	108.3	O5—C17—C8	115.10 (12)
C7—C6—H6B	108.3	O2—C18—O1	121.13 (15)
C5—C6—H6B	108.3	O2—C18—C4	129.41 (14)
H6A—C6—H6B	107.4	O1—C18—C4	109.46 (13)
C8—C7—C6	113.24 (11)	C5—C19—H19A	109.5
C8—C7—H7A	108.9	C5—C19—H19B	109.5
C6—C7—H7A	108.9	H19A—C19—H19B	109.5
C8—C7—H7B	108.9	C5—C19—H19C	109.5
C6—C7—H7B	108.9	H19A—C19—H19C	109.5
H7A—C7—H7B	107.7	H19B—C19—H19C	109.5
C17—C8—C7	113.08 (12)	C9—C20—H20A	109.5
C17—C8—C9	111.68 (11)	C9—C20—H20B	109.5
C7—C8—C9	114.33 (11)	H20A—C20—H20B	109.5
C17—C8—H8A	105.6	C9—C20—H20C	109.5
C7—C8—H8A	105.6	H20A—C20—H20C	109.5
C9—C8—H8A	105.6	H20B—C20—H20C	109.5
C20—C9—C10	114.15 (11)
C18—O1—C2—C1	−94.59 (13)	C2—C1—C10—C9	−121.36 (14)
C18—O1—C2—C3	23.98 (14)	C2—C1—C10—C5	13.4 (2)
C10—C1—C2—O1	64.85 (17)	C19—C5—C10—C9	−116.27 (13)
C10—C1—C2—C3	−48.58 (18)	C6—C5—C10—C9	2.04 (17)
O1—C2—C3—O3	−164.81 (11)	C4—C5—C10—C9	124.18 (13)
C1—C2—C3—O3	−46.95 (16)	C19—C5—C10—C1	110.25 (14)
O1—C2—C3—C4	−42.52 (13)	C6—C5—C10—C1	−131.43 (13)
C1—C2—C3—C4	75.34 (15)	C4—C5—C10—C1	−9.29 (18)
O3—C3—C4—O4	−77.80 (16)	C20—C9—C11—C12	124.47 (13)
C2—C3—C4—O4	161.55 (13)	C10—C9—C11—C12	−110.95 (14)
O3—C3—C4—C18	163.86 (12)	C8—C9—C11—C12	3.10 (18)
C2—C3—C4—C18	43.21 (13)	C17—O5—C12—C13	171.56 (12)
O3—C3—C4—C5	48.87 (17)	C17—O5—C12—C11	50.87 (15)
C2—C3—C4—C5	−71.78 (15)	C9—C11—C12—O5	−51.14 (16)
O4—C4—C5—C19	52.16 (16)	C9—C11—C12—C13	−168.04 (13)
C3—C4—C5—C19	−77.48 (15)	O5—C12—C13—C16	105.01 (16)
C18—C4—C5—C19	174.28 (12)	C11—C12—C13—C16	−136.03 (16)
O4—C4—C5—C6	−64.40 (15)	O5—C12—C13—C14	−76.91 (17)
C3—C4—C5—C6	165.96 (12)	C11—C12—C13—C14	42.1 (2)
C18—C4—C5—C6	57.71 (14)	C16—C13—C14—C15	0.54 (17)
O4—C4—C5—C10	170.36 (13)	C12—C13—C14—C15	−177.84 (14)
C3—C4—C5—C10	40.72 (17)	C13—C14—C15—O7	−0.09 (18)
C18—C4—C5—C10	−67.53 (15)	C16—O7—C15—C14	−0.40 (17)
C19—C5—C6—C7	73.55 (14)	C14—C13—C16—O7	−0.81 (17)
C4—C5—C6—C7	−168.95 (12)	C12—C13—C16—O7	177.62 (13)
C10—C5—C6—C7	−44.25 (16)	C15—O7—C16—C13	0.76 (16)
C5—C6—C7—C8	29.86 (17)	C12—O5—C17—O6	179.82 (13)
C6—C7—C8—C17	155.77 (13)	C12—O5—C17—C8	0.97 (18)
C6—C7—C8—C9	26.47 (18)	C7—C8—C17—O6	−2.4 (2)
C17—C8—C9—C20	−71.31 (15)	C9—C8—C17—O6	128.28 (16)
C7—C8—C9—C20	58.69 (15)	C7—C8—C17—O5	176.37 (12)
C17—C8—C9—C10	163.84 (13)	C9—C8—C17—O5	−52.99 (17)
C7—C8—C9—C10	−66.16 (16)	C2—O1—C18—O2	−174.62 (13)
C17—C8—C9—C11	47.30 (17)	C2—O1—C18—C4	5.10 (14)
C7—C8—C9—C11	177.30 (12)	O4—C4—C18—O2	27.2 (2)
C20—C9—C10—C1	61.69 (15)	C3—C4—C18—O2	148.19 (15)
C8—C9—C10—C1	−174.68 (12)	C5—C4—C18—O2	−93.50 (18)
C11—C9—C10—C1	−59.14 (16)	O4—C4—C18—O1	−152.46 (11)
C20—C9—C10—C5	−74.33 (14)	C3—C4—C18—O1	−31.50 (13)
C8—C9—C10—C5	49.30 (16)	C5—C4—C18—O1	86.81 (13)
C11—C9—C10—C5	164.85 (12)

D—H···A	D—H	H···A	D···A	D—H···A
O3—H1O3···O5i	0.86 (3)	2.54 (3)	3.1305 (15)	127 (2)
O4—H1O4···O6i	0.87 (3)	2.12 (3)	2.9708 (14)	165 (2)
C3—H3A···O5i	0.98	2.39	3.1295 (16)	131
C6—H6A···O2	0.97	2.43	3.1718 (19)	133
C8—H8A···O2ii	0.98	2.29	3.2113 (19)	157
C19—H19C···O3	0.96	2.31	2.9489 (18)	124
C20—H20B···O7iii	0.96	2.53	3.4613 (18)	164

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H1O3⋯O5i	0.86 (3)	2.54 (3)	3.1305 (15)	127 (2)
O4—H1O4⋯O6i	0.87 (3)	2.12 (3)	2.9708 (14)	165 (2)
C3—H3A⋯O5i	0.98	2.39	3.1295 (16)	131
C6—H6A⋯O2	0.97	2.43	3.1718 (19)	133
C8—H8A⋯O2ii	0.98	2.29	3.2113 (19)	157
C19—H19C⋯O3	0.96	2.31	2.9489 (18)	124
C20—H20B⋯O7iii	0.96	2.53	3.4613 (18)	164

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