Unusual hemiacetal structure derived from Salvinorin A.

The salvinorin A analog dimethyl (2R,3aR,4R,6aR,7R,9S,9aS,9bS)-2-(3-fur-yl)-9,9a-dihydr-oxy-3a,6a-dimethyl-dodeca-hydro-benzo[de]chromene-4,7-dicarboxyl-ate, C(22)H(30)O(8), has a relatively simple spatial arrangement in which mol-ecules are linked into layers by two pairs of O-H⋯O hydrogen bonds. Each mol-ecule has as the central feature a dodeca-hydro-1H-phenalene ring system. Its three six-membered rings are in the chair conformation, with two axial methyl groups, one axial OH, and one equatorial OH, these OH groups being directly responsible for linking of the mol-ecules in the crystal structure.

Related literature

For the synthesis of analogs of salvinorin A, see: Bikbulatov et al. (2007 ▶); Lee et al. (2006 ▶); Beguin et al. (2006 ▶); Stewart et al. (2006 ▶) and references cited therein. For modifications of salvinorin A with changed pharmacological profile, see: Rothman et al. (2007 ▶); Groer et al. (2007 ▶); Tidgewell et al. (2006 ▶); Harding et al. (2005 ▶, 2006 ▶).

Experimental

Crystal data

C22H30O8

M = 422.46

Monoclinic,

a = 11.6801 (5) Å

b = 6.0522 (3) Å

c = 15.3739 (6) Å

β = 107.678 (2)°

V = 1035.47 (8) Å3

Z = 2

Cu Kα radiation

μ = 0.86 mm−1

T = 296 (2) K

0.32 × 0.15 × 0.13 mm

Data collection

Bruker SMART CCD area-detector diffractometer

Absorption correction: none

18724 measured reflections

3726 independent reflections

3615 reflections with I > 2σ(I)

R int = 0.037

Refinement

R[F 2 > 2σ(F 2)] = 0.037

wR(F 2) = 0.096

S = 1.05

3726 reflections

277 parameters

1 restraint

H-atom parameters constrained

Δρmax = 0.41 e Å−3

Δρmin = −0.21 e Å−3

Absolute structure: Flack (1983 ▶), 1587 Friedel pairs

Flack parameter: 0.14 (18)

Data collection: SMART (Bruker, 2003 ▶); cell refinement: SAINT (Bruker, 2003 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Crystal structure: contains datablocks I, global. DOI: 10.1107/S160053680800144X/gw2037sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S160053680800144X/gw2037Isup2.hkl

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

C22H30O8	F000 = 452
Mr = 422.46	Dx = 1.355 Mg m−3
Monoclinic, P21	Cu Kα radiation λ = 1.54178 Å
Hall symbol: P 2yb	Cell parameters from 8551 reflections
a = 11.6801 (5) Å	θ = 3.0–69.4º
b = 6.0522 (3) Å	µ = 0.86 mm−1
c = 15.3739 (6) Å	T = 296 (2) K
β = 107.678 (2)º	Blocks, colourless
V = 1035.47 (8) Å3	0.32 × 0.15 × 0.13 mm
Z = 2

Bruker SMART CCD area-detector diffractometer	3615 reflections with I > 2σ(I)
Monochromator: graphite	Rint = 0.037
T = 100 K	θmax = 69.4º
phi and ω scans	θmin = 3.0º
Absorption correction: none	h = −13→13
18724 measured reflections	k = −7→7
3726 independent reflections	l = −18→18

Refinement on F2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F2 > 2σ(F2)] = 0.037	w = 1/[σ2(Fo2) + (0.0458P)2 + 0.4492P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.096	(Δ/σ)max < 0.001
S = 1.05	Δρmax = 0.42 e Å−3
3726 reflections	Δρmin = −0.21 e Å−3
277 parameters	Extinction correction: none
1 restraint	Absolute structure: Flack (1983), 1587 Friedel pairs
Primary atom site location: structure-invariant direct methods	Flack parameter: 0.14 (18)
Secondary atom site location: difference Fourier map

Experimental. The structure was solved using Direct methods and difference Fourier techniques SHELXTL, V6.12 (Bruker, 2003). Hydrogen atoms were placed in their expected chemical positions using the HFIX command and were included in the final cycles of least squares with isotropic Uij related to the atoms ridden upon. All non-hydrogen atoms were refined anisotropically.Structure solution, refinement, graphics and generation of publication materials were performed by using SHELXTL, V6.12 software. Additional details of data collection and structure refinement are given in Table 1.

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
C2	0.18522 (17)	0.9011 (4)	0.91971 (13)	0.0308 (5)
H2	0.1571	0.7482	0.9184	0.037*
C5	0.15034 (17)	0.9159 (3)	0.58226 (12)	0.0226 (4)
H5A	0.1171	0.7690	0.5668	0.027*
H5B	0.1226	1.0076	0.5282	0.027*
C3	0.12566 (17)	1.0070 (4)	0.82782 (12)	0.0261 (4)
H3A	0.1552	1.1568	0.8281	0.031*
H3B	0.0396	1.0144	0.8176	0.031*
C6	0.28737 (16)	0.9033 (3)	0.61198 (12)	0.0217 (4)
H6A	0.3195	1.0521	0.6224	0.026*
H6B	0.3122	0.8401	0.5626	0.026*
C4	0.10549 (16)	1.0123 (3)	0.65832 (12)	0.0209 (4)
H4	0.1380	1.1622	0.6711	0.025*
C8	0.54094 (17)	0.7152 (4)	0.82950 (13)	0.0283 (4)
H8A	0.5286	0.5568	0.8302	0.034*
H8B	0.6268	0.7428	0.8472	0.034*
C9	0.48763 (17)	0.8258 (3)	0.89657 (12)	0.0256 (4)
H9	0.4971	0.9857	0.8914	0.031*
C7	0.48158 (17)	0.8048 (3)	0.73302 (12)	0.0230 (4)
H7	0.4950	0.9648	0.7349	0.028*
C3A	0.15070 (16)	0.8761 (3)	0.74901 (11)	0.0202 (4)
C6A	0.34211 (16)	0.7655 (3)	0.69886 (12)	0.0197 (4)
C9A	0.35251 (18)	0.7770 (3)	0.87112 (13)	0.0239 (4)
C9B	0.29098 (16)	0.8644 (3)	0.77341 (11)	0.0191 (4)
H9B	0.3154	1.0198	0.7767	0.023*
C10	0.16237 (19)	1.0186 (5)	0.99865 (14)	0.0448 (7)
C12	0.1441 (3)	1.0759 (8)	1.13703 (17)	0.0705 (12)
H12	0.1433	1.0539	1.1967	0.085*
C11	0.1675 (3)	0.9226 (8)	1.0830 (2)	0.0778 (12)
H11	0.1846	0.7751	1.0985	0.093*
C13	0.1359 (3)	1.2334 (7)	1.00599 (18)	0.0751 (12)
H13	0.1281	1.3414	0.9615	0.090*
C16	−0.03024 (17)	1.0299 (3)	0.62641 (12)	0.0252 (4)
C18	0.54524 (17)	0.7069 (4)	0.66942 (13)	0.0261 (4)
C14	0.08432 (17)	0.6535 (3)	0.73785 (13)	0.0257 (4)
H14A	0.1270	0.5548	0.7856	0.039*
H14B	0.0801	0.5906	0.6796	0.039*
H14C	0.0045	0.6763	0.7414	0.039*
C15	0.31545 (17)	0.5190 (3)	0.67784 (13)	0.0259 (4)
H15A	0.2316	0.5000	0.6460	0.039*
H15B	0.3359	0.4370	0.7339	0.039*
H15C	0.3623	0.4661	0.6405	0.039*
C19	0.6056 (3)	0.7648 (5)	0.53744 (18)	0.0490 (7)
H19A	0.6898	0.7427	0.5672	0.073*
H19B	0.5951	0.8701	0.4890	0.073*
H19C	0.5692	0.6270	0.5128	0.073*
C17	−0.1957 (2)	1.2172 (6)	0.65095 (18)	0.0505 (7)
H17A	−0.2322	1.2419	0.5868	0.076*
H17B	−0.2122	1.3404	0.6846	0.076*
H17C	−0.2279	1.0848	0.6688	0.076*
O1	0.31411 (11)	0.9003 (3)	0.93685 (8)	0.0273 (3)
O3	0.32773 (13)	0.5526 (2)	0.87711 (9)	0.0286 (3)
H3	0.3709	0.5030	0.9256	0.043*
O5	−0.09773 (12)	0.9134 (3)	0.57030 (10)	0.0352 (4)
O6	−0.06776 (13)	1.1939 (3)	0.66985 (10)	0.0349 (4)
O2	0.54549 (13)	0.7663 (3)	0.98856 (9)	0.0311 (3)
H2A	0.5935	0.6663	0.9902	0.047*
O7	0.58818 (15)	0.5249 (3)	0.67619 (11)	0.0429 (4)
O8	0.54884 (15)	0.8474 (3)	0.60324 (11)	0.0383 (4)
O4	0.1223 (2)	1.2643 (7)	1.09199 (17)	0.1192 (16)

	U11	U22	U33	U12	U13	U23
C2	0.0193 (9)	0.0538 (13)	0.0210 (9)	−0.0075 (10)	0.0087 (7)	−0.0039 (9)
C5	0.0235 (9)	0.0264 (9)	0.0172 (8)	−0.0001 (8)	0.0053 (7)	0.0016 (7)
C3	0.0159 (9)	0.0401 (11)	0.0237 (9)	−0.0026 (8)	0.0078 (7)	−0.0048 (9)
C6	0.0233 (9)	0.0242 (9)	0.0195 (8)	−0.0030 (8)	0.0093 (7)	−0.0008 (7)
C4	0.0202 (9)	0.0206 (9)	0.0226 (9)	−0.0014 (7)	0.0074 (7)	−0.0020 (7)
C8	0.0190 (9)	0.0402 (12)	0.0239 (9)	0.0031 (8)	0.0037 (8)	−0.0023 (8)
C9	0.0222 (10)	0.0362 (11)	0.0178 (8)	−0.0017 (8)	0.0051 (7)	−0.0020 (8)
C7	0.0198 (9)	0.0281 (10)	0.0215 (9)	−0.0020 (8)	0.0067 (7)	−0.0046 (7)
C3A	0.0161 (9)	0.0257 (9)	0.0185 (8)	−0.0028 (7)	0.0050 (7)	−0.0016 (7)
C6A	0.0174 (9)	0.0236 (9)	0.0180 (8)	−0.0013 (7)	0.0054 (7)	−0.0011 (7)
C9A	0.0222 (10)	0.0311 (10)	0.0199 (8)	−0.0026 (8)	0.0084 (7)	0.0001 (8)
C9B	0.0174 (9)	0.0207 (9)	0.0190 (8)	−0.0034 (7)	0.0053 (7)	−0.0003 (7)
C10	0.0168 (10)	0.098 (2)	0.0218 (10)	−0.0058 (12)	0.0089 (8)	−0.0109 (12)
C12	0.0373 (15)	0.160 (4)	0.0190 (11)	0.0052 (19)	0.0150 (10)	−0.0089 (18)
C11	0.082 (2)	0.126 (3)	0.0380 (15)	−0.036 (2)	0.0370 (15)	−0.0145 (18)
C13	0.072 (2)	0.120 (3)	0.0285 (13)	0.050 (2)	0.0076 (13)	−0.0206 (16)
C16	0.0219 (9)	0.0290 (10)	0.0249 (9)	0.0025 (8)	0.0075 (8)	0.0039 (8)
C18	0.0175 (9)	0.0341 (11)	0.0254 (9)	0.0010 (8)	0.0048 (7)	−0.0053 (8)
C14	0.0209 (9)	0.0306 (10)	0.0243 (9)	−0.0062 (8)	0.0048 (7)	0.0024 (8)
C15	0.0252 (10)	0.0257 (10)	0.0254 (9)	0.0003 (8)	0.0060 (8)	−0.0028 (8)
C19	0.0518 (16)	0.0625 (17)	0.0461 (13)	0.0102 (13)	0.0350 (12)	0.0024 (13)
C17	0.0283 (11)	0.0711 (18)	0.0494 (14)	0.0197 (12)	0.0077 (11)	−0.0069 (13)
O1	0.0180 (7)	0.0454 (8)	0.0191 (6)	−0.0045 (6)	0.0066 (5)	−0.0041 (6)
O3	0.0278 (7)	0.0308 (7)	0.0235 (6)	−0.0033 (6)	0.0022 (5)	0.0080 (6)
O5	0.0237 (7)	0.0461 (9)	0.0313 (7)	−0.0011 (7)	0.0015 (6)	−0.0102 (7)
O6	0.0259 (7)	0.0379 (8)	0.0393 (8)	0.0089 (7)	0.0074 (6)	−0.0058 (7)
O2	0.0292 (8)	0.0361 (8)	0.0244 (7)	0.0024 (6)	0.0027 (6)	−0.0009 (6)
O7	0.0443 (9)	0.0492 (10)	0.0389 (8)	0.0204 (8)	0.0181 (7)	0.0006 (8)
O8	0.0409 (9)	0.0458 (10)	0.0395 (8)	0.0042 (7)	0.0290 (7)	0.0025 (7)
O4	0.0566 (14)	0.244 (5)	0.0456 (13)	0.063 (2)	−0.0011 (11)	−0.063 (2)

C2—O1	1.447 (2)	C9A—O1	1.433 (2)
C2—C10	1.499 (3)	C9A—C9B	1.548 (2)
C2—C3	1.515 (3)	C9B—H9B	0.9800
C2—H2	0.9800	C10—C13	1.349 (5)
C5—C6	1.527 (3)	C10—C11	1.405 (4)
C5—C4	1.535 (2)	C12—O4	1.318 (6)
C5—H5A	0.9700	C12—C11	1.328 (5)
C5—H5B	0.9700	C12—H12	0.9300
C3—C3A	1.548 (3)	C11—H11	0.9300
C3—H3A	0.9700	C13—O4	1.391 (3)
C3—H3B	0.9700	C13—H13	0.9300
C6—C6A	1.540 (2)	C16—O5	1.204 (2)
C6—H6A	0.9700	C16—O6	1.342 (3)
C6—H6B	0.9700	C18—O7	1.202 (3)
C4—C16	1.514 (2)	C18—O8	1.336 (3)
C4—C3A	1.567 (2)	C14—H14A	0.9600
C4—H4	0.9800	C14—H14B	0.9600
C8—C9	1.513 (3)	C14—H14C	0.9600
C8—C7	1.533 (3)	C15—H15A	0.9600
C8—H8A	0.9700	C15—H15B	0.9600
C8—H8B	0.9700	C15—H15C	0.9600
C9—O2	1.416 (2)	C19—O8	1.456 (3)
C9—C9A	1.535 (3)	C19—H19A	0.9600
C9—H9	0.9800	C19—H19B	0.9600
C7—C18	1.517 (3)	C19—H19C	0.9600
C7—C6A	1.571 (2)	C17—O6	1.440 (3)
C7—H7	0.9800	C17—H17A	0.9600
C3A—C14	1.538 (3)	C17—H17B	0.9600
C3A—C9B	1.568 (2)	C17—H17C	0.9600
C6A—C15	1.538 (3)	O3—H3	0.8200
C6A—C9B	1.563 (2)	O2—H2A	0.8200
C9A—O3	1.398 (2)
O1—C2—C10	106.57 (15)	O3—C9A—O1	110.13 (15)
O1—C2—C3	109.20 (15)	O3—C9A—C9	112.80 (17)
C10—C2—C3	114.2 (2)	O1—C9A—C9	103.77 (15)
O1—C2—H2	108.9	O3—C9A—C9B	110.57 (15)
C10—C2—H2	108.9	O1—C9A—C9B	110.73 (15)
C3—C2—H2	108.9	C9—C9A—C9B	108.67 (15)
C6—C5—C4	111.12 (14)	C9A—C9B—C6A	114.36 (15)
C6—C5—H5A	109.4	C9A—C9B—C3A	113.02 (14)
C4—C5—H5A	109.4	C6A—C9B—C3A	116.49 (14)
C6—C5—H5B	109.4	C9A—C9B—H9B	103.6
C4—C5—H5B	109.4	C6A—C9B—H9B	103.6
H5A—C5—H5B	108.0	C3A—C9B—H9B	103.6
C2—C3—C3A	111.77 (17)	C13—C10—C11	105.5 (3)
C2—C3—H3A	109.3	C13—C10—C2	128.8 (3)
C3A—C3—H3A	109.3	C11—C10—C2	125.6 (3)
C2—C3—H3B	109.3	O4—C12—C11	108.6 (3)
C3A—C3—H3B	109.3	O4—C12—H12	125.7
H3A—C3—H3B	107.9	C11—C12—H12	125.7
C5—C6—C6A	114.07 (15)	C12—C11—C10	109.2 (4)
C5—C6—H6A	108.7	C12—C11—H11	125.4
C6A—C6—H6A	108.7	C10—C11—H11	125.4
C5—C6—H6B	108.7	C10—C13—O4	107.7 (3)
C6A—C6—H6B	108.7	C10—C13—H13	126.1
H6A—C6—H6B	107.6	O4—C13—H13	126.1
C16—C4—C5	110.25 (14)	O5—C16—O6	123.23 (18)
C16—C4—C3A	111.23 (15)	O5—C16—C4	125.74 (18)
C5—C4—C3A	112.15 (15)	O6—C16—C4	111.03 (16)
C16—C4—H4	107.7	O7—C18—O8	122.7 (2)
C5—C4—H4	107.7	O7—C18—C7	125.1 (2)
C3A—C4—H4	107.7	O8—C18—C7	112.15 (17)
C9—C8—C7	110.12 (16)	C3A—C14—H14A	109.5
C9—C8—H8A	109.6	C3A—C14—H14B	109.5
C7—C8—H8A	109.6	H14A—C14—H14B	109.5
C9—C8—H8B	109.6	C3A—C14—H14C	109.5
C7—C8—H8B	109.6	H14A—C14—H14C	109.5
H8A—C8—H8B	108.2	H14B—C14—H14C	109.5
O2—C9—C8	113.43 (16)	C6A—C15—H15A	109.5
O2—C9—C9A	110.34 (15)	C6A—C15—H15B	109.5
C8—C9—C9A	110.20 (15)	H15A—C15—H15B	109.5
O2—C9—H9	107.5	C6A—C15—H15C	109.5
C8—C9—H9	107.5	H15A—C15—H15C	109.5
C9A—C9—H9	107.5	H15B—C15—H15C	109.5
C18—C7—C8	108.61 (16)	O8—C19—H19A	109.5
C18—C7—C6A	112.77 (14)	O8—C19—H19B	109.5
C8—C7—C6A	112.85 (15)	H19A—C19—H19B	109.5
C18—C7—H7	107.4	O8—C19—H19C	109.5
C8—C7—H7	107.4	H19A—C19—H19C	109.5
C6A—C7—H7	107.4	H19B—C19—H19C	109.5
C14—C3A—C3	109.09 (16)	O6—C17—H17A	109.5
C14—C3A—C4	109.84 (14)	O6—C17—H17B	109.5
C3—C3A—C4	109.53 (15)	H17A—C17—H17B	109.5
C14—C3A—C9B	116.24 (16)	O6—C17—H17C	109.5
C3—C3A—C9B	105.55 (14)	H17A—C17—H17C	109.5
C4—C3A—C9B	106.38 (14)	H17B—C17—H17C	109.5
C15—C6A—C6	109.81 (15)	C9A—O1—C2	113.84 (14)
C15—C6A—C9B	115.31 (16)	C9A—O3—H3	109.5
C6—C6A—C9B	106.15 (14)	C16—O6—C17	116.61 (17)
C15—C6A—C7	109.91 (15)	C9—O2—H2A	109.5
C6—C6A—C7	108.86 (15)	C18—O8—C19	115.88 (19)
C9B—C6A—C7	106.57 (13)	C12—O4—C13	108.9 (3)

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···O2i	0.82	1.99	2.757 (2)	155
O2—H2A···O1i	0.82	2.07	2.787 (2)	146

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H3⋯O2i	0.82	1.99	2.757 (2)	155
O2—H2A⋯O1i	0.82	2.07	2.787 (2)	146

Symmetry code: (i) .