5α-Androst-3-en-17β-yl acetate.

In the crystal structure of the title compound, C(21)H(32)O(2), ring A is highly distorted, with a conformation inter-mediate between 10β-sofa and 1α,10β-half chair; rings B and C have slightly flattened chair conformations. Ring D assumes an unusual 13β-envelope conformation, probably induced by the acet-oxy substituent. Cohesion of the crystal structure is due only to weak van der Waals inter-actions.

Related literature

For structure–activity relationships (SAR) of steroids with modified A and D rings as aromatase inhibitors, see: Cepa et al. (2005 ▶, 2008 ▶). For the synthesis and assignment of the absolute configuration, see: Cepa et al. (2008 ▶). For a related structure, see Paixão et al. (2001 ▶). For reference bond-length data, see: Allen et al. 1987 ▶. For conformational details, see: Duax & Norton (1975 ▶); Cremer & Pople (1975 ▶); Altona et al. (1968 ▶).

Experimental

Crystal data

C21H32O2

M = 316.47

Monoclinic,

a = 14.7728 (3) Å

b = 6.2673 (1) Å

c = 20.2514 (5) Å

β = 99.874 (1)°

V = 1847.21 (7) Å3

Z = 4

Mo Kα radiation

μ = 0.07 mm−1

T = 293 K

0.41 × 0.39 × 0.10 mm

Data collection

Bruker APEXII CCD area-detector diffractometer

Absorption correction: multi-scan (SADABS; Sheldrick, 2000 ▶) T min = 0.971, T max = 0.993

22420 measured reflections

2292 independent reflections

1554 reflections with I > 2σ(I)

R int = 0.030

Refinement

R[F 2 > 2σ(F 2)] = 0.045

wR(F 2) = 0.102

S = 1.08

2292 reflections

211 parameters

1 restraint

H-atom parameters constrained

Δρmax = 0.13 e Å−3

Δρmin = −0.17 e Å−3

Data collection: APEX2 (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: ORTEPII (Johnson, 1976 ▶); software used to prepare material for publication: SHELXL97.

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809053264/wn2371sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809053264/wn2371Isup2.hkl

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

C21H32O2	F(000) = 696
Mr = 316.47	Dx = 1.138 Mg m−3
Monoclinic, C2	Mo Kα radiation, λ = 0.71073 Å
a = 14.7728 (3) Å	Cell parameters from 7585 reflections
b = 6.2673 (1) Å	θ = 2.8–21.5°
c = 20.2514 (5) Å	µ = 0.07 mm−1
β = 99.874 (1)°	T = 293 K
V = 1847.21 (7) Å3	Prism, colourless
Z = 4	0.41 × 0.39 × 0.10 mm

Bruker APEXII CCD area-detector diffractometer	2292 independent reflections
Radiation source: fine-focus sealed tube	1554 reflections with I > 2σ(I)
graphite	Rint = 0.030
φ and ω scans	θmax = 27.9°, θmin = 2.0°
Absorption correction: multi-scan (SADABS; Sheldrick, 2000)	h = −18→18
Tmin = 0.971, Tmax = 0.993	k = −8→8
22420 measured reflections	l = −26→25

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.045	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.102	H-atom parameters constrained
S = 1.08	w = 1/[σ2(Fo2) + (0.0455P)2 + 0.3162P] where P = (Fo2 + 2Fc2)/3
2292 reflections	(Δ/σ)max < 0.001
211 parameters	Δρmax = 0.13 e Å−3
1 restraint	Δρmin = −0.17 e Å−3

Experimental. IR νmax(KBr) cm-1: 3015 (═C–H), 1733 (C═O); 1H NMR (300 MHz, CDCl3) δ: 0.77 (3H, s, 18-H3)*, 0.79 (3H, s, 19-H3)*, 2.03 (3H, s, CH3COO), 4.59 (1H, dd, J17α,16α=7.9, J17α,16β=7.9, 17α-H), 5.27 (1H, ddd, J4,3=9.8, J4,5α=4.5, J4,2α=2.5, 4-H), 5.54 (1H, ddd, J3,4=9.8, J3,2β=6.3, J3,2α=3.2, 3-H); 13C NMR (75.6 MHz, DMSO-d6) δ: 11.8 (C-19)**, 12.2 (C-18)**, 20.5, 21.1, 23.4, 23.5, 27.2, 27.5, 31.5, 34.1, 34.9, 35.3, 36.9, 42.7, 45.8 (C-5), 50.7, 53.3, 82.9 (C-17), 125.4 (C-3), 131.2 (C-4); 171.2 (C═O); EIMS m/z 316 (M+, 100%). *,** Signals may be interchangeable.

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 taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used 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 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 > σ(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
C1	0.19131 (17)	0.6621 (5)	0.62336 (12)	0.0534 (7)
H1A	0.1677	0.7480	0.6565	0.064*
H1B	0.2252	0.7558	0.5983	0.064*
C2	0.11018 (18)	0.5657 (6)	0.57530 (14)	0.0724 (9)
H2A	0.0626	0.5259	0.6006	0.087*
H2B	0.0848	0.6733	0.5429	0.087*
C3	0.13589 (19)	0.3740 (5)	0.53863 (13)	0.0633 (8)
H3	0.0923	0.3151	0.5050	0.076*
C4	0.21769 (18)	0.2854 (5)	0.55206 (12)	0.0525 (7)
H4	0.2288	0.1648	0.5279	0.063*
C5	0.29364 (15)	0.3678 (4)	0.60392 (11)	0.0428 (6)
H5	0.3265	0.4721	0.5808	0.051*
C6	0.36450 (17)	0.2002 (4)	0.63145 (13)	0.0508 (7)
H6A	0.3366	0.0950	0.6568	0.061*
H6B	0.3858	0.1278	0.5946	0.061*
C7	0.44506 (15)	0.3031 (4)	0.67622 (12)	0.0480 (7)
H7A	0.4773	0.3944	0.6493	0.058*
H7B	0.4873	0.1928	0.6958	0.058*
C8	0.41595 (15)	0.4351 (4)	0.73221 (11)	0.0385 (6)
H8	0.3911	0.3380	0.7626	0.046*
C9	0.34047 (14)	0.5989 (4)	0.70474 (10)	0.0353 (5)
H9	0.3681	0.6951	0.6756	0.042*
C10	0.25731 (14)	0.4943 (4)	0.65963 (11)	0.0394 (6)
C11	0.31613 (15)	0.7380 (4)	0.76137 (11)	0.0434 (6)
H11A	0.2728	0.8468	0.7421	0.052*
H11B	0.2860	0.6500	0.7905	0.052*
C12	0.39942 (15)	0.8466 (4)	0.80345 (11)	0.0429 (6)
H12A	0.4253	0.9487	0.7759	0.052*
H12B	0.3800	0.9237	0.8401	0.052*
C13	0.47280 (15)	0.6831 (4)	0.83163 (11)	0.0378 (6)
C14	0.49663 (14)	0.5547 (4)	0.77246 (11)	0.0399 (6)
H14	0.5161	0.6592	0.7417	0.048*
C15	0.58350 (16)	0.4311 (5)	0.80303 (13)	0.0599 (8)
H15A	0.6212	0.4002	0.7694	0.072*
H15B	0.5679	0.2981	0.8229	0.072*
C16	0.63351 (16)	0.5840 (5)	0.85708 (13)	0.0572 (7)
H16A	0.6450	0.5148	0.9006	0.069*
H16B	0.6917	0.6301	0.8458	0.069*
C17	0.56810 (15)	0.7744 (4)	0.85757 (12)	0.0447 (6)
H17	0.5826	0.8834	0.8263	0.054*
C18	0.44041 (17)	0.5428 (5)	0.88509 (12)	0.0530 (7)
H18A	0.4859	0.4358	0.8998	0.080*
H18B	0.3835	0.4751	0.8664	0.080*
H18C	0.4316	0.6296	0.9225	0.080*
C19	0.20421 (17)	0.3490 (5)	0.70079 (13)	0.0562 (7)
H19A	0.1693	0.4350	0.7265	0.084*
H19B	0.2468	0.2625	0.7305	0.084*
H19C	0.1634	0.2587	0.6711	0.084*
C17A	0.64397 (18)	0.9967 (5)	0.94474 (13)	0.0538 (7)
C17B	0.6399 (2)	1.0837 (7)	1.01266 (14)	0.0876 (11)
H17B	0.5804	1.0557	1.0238	0.131*
H17C	0.6505	1.2348	1.0129	0.131*
H17D	0.6862	1.0165	1.0450	0.131*
O17A	0.57234 (11)	0.8688 (3)	0.92319 (8)	0.0531 (5)
O17B	0.70289 (13)	1.0344 (4)	0.91272 (10)	0.0760 (7)

	U11	U22	U33	U12	U13	U23
C1	0.0468 (15)	0.0607 (18)	0.0501 (15)	0.0143 (13)	0.0005 (13)	−0.0053 (14)
C2	0.0503 (16)	0.094 (2)	0.0664 (19)	0.0145 (18)	−0.0084 (15)	−0.021 (2)
C3	0.0517 (17)	0.085 (2)	0.0500 (16)	−0.0041 (17)	−0.0007 (13)	−0.0134 (17)
C4	0.0549 (16)	0.0559 (16)	0.0456 (15)	−0.0013 (14)	0.0061 (13)	−0.0085 (13)
C5	0.0421 (13)	0.0468 (14)	0.0400 (13)	0.0028 (13)	0.0082 (11)	0.0007 (12)
C6	0.0507 (16)	0.0492 (15)	0.0520 (15)	0.0099 (13)	0.0074 (13)	−0.0120 (13)
C7	0.0422 (14)	0.0486 (15)	0.0530 (15)	0.0155 (12)	0.0072 (12)	−0.0062 (13)
C8	0.0365 (12)	0.0400 (13)	0.0394 (13)	0.0057 (11)	0.0079 (10)	0.0030 (11)
C9	0.0356 (12)	0.0359 (13)	0.0354 (12)	0.0034 (11)	0.0085 (10)	0.0034 (11)
C10	0.0324 (12)	0.0456 (14)	0.0399 (13)	0.0033 (11)	0.0059 (10)	0.0007 (11)
C11	0.0379 (13)	0.0472 (16)	0.0437 (14)	0.0117 (12)	0.0028 (11)	−0.0036 (12)
C12	0.0437 (14)	0.0432 (14)	0.0421 (13)	0.0076 (12)	0.0079 (11)	−0.0051 (12)
C13	0.0327 (12)	0.0441 (14)	0.0367 (13)	0.0037 (10)	0.0063 (10)	0.0037 (11)
C14	0.0325 (12)	0.0421 (14)	0.0452 (13)	0.0073 (11)	0.0074 (10)	0.0029 (12)
C15	0.0391 (14)	0.070 (2)	0.0666 (18)	0.0160 (14)	−0.0019 (13)	−0.0073 (16)
C16	0.0378 (13)	0.073 (2)	0.0582 (16)	0.0059 (15)	0.0001 (12)	0.0014 (16)
C17	0.0382 (13)	0.0567 (15)	0.0389 (14)	−0.0024 (12)	0.0059 (11)	0.0019 (12)
C18	0.0490 (15)	0.0644 (17)	0.0459 (15)	−0.0046 (14)	0.0087 (12)	0.0078 (14)
C19	0.0474 (14)	0.0678 (18)	0.0556 (15)	−0.0138 (14)	0.0148 (12)	−0.0053 (15)
C17A	0.0412 (15)	0.0629 (18)	0.0527 (17)	−0.0044 (14)	−0.0049 (13)	0.0013 (14)
C17B	0.070 (2)	0.124 (3)	0.0644 (19)	−0.028 (2)	0.0012 (15)	−0.027 (2)
O17A	0.0442 (10)	0.0721 (12)	0.0418 (9)	−0.0114 (10)	0.0045 (7)	−0.0088 (10)
O17B	0.0516 (11)	0.1011 (17)	0.0758 (14)	−0.0238 (13)	0.0125 (10)	−0.0063 (13)

C1—C2	1.533 (3)	C11—H11B	0.9700
C1—C10	1.533 (3)	C12—C13	1.529 (3)
C1—H1A	0.9700	C12—H12A	0.9700
C1—H1B	0.9700	C12—H12B	0.9700
C2—C3	1.495 (4)	C13—C17	1.527 (3)
C2—H2A	0.9700	C13—C18	1.534 (3)
C2—H2B	0.9700	C13—C14	1.534 (3)
C3—C4	1.315 (3)	C14—C15	1.536 (3)
C3—H3	0.9300	C14—H14	0.9800
C4—C5	1.491 (3)	C15—C16	1.545 (4)
C4—H4	0.9300	C15—H15A	0.9700
C5—C6	1.520 (3)	C15—H15B	0.9700
C5—C10	1.548 (3)	C16—C17	1.536 (4)
C5—H5	0.9800	C16—H16A	0.9700
C6—C7	1.511 (3)	C16—H16B	0.9700
C6—H6A	0.9700	C17—O17A	1.446 (3)
C6—H6B	0.9700	C17—H17	0.9800
C7—C8	1.524 (3)	C18—H18A	0.9600
C7—H7A	0.9700	C18—H18B	0.9600
C7—H7B	0.9700	C18—H18C	0.9600
C8—C14	1.521 (3)	C19—H19A	0.9600
C8—C9	1.547 (3)	C19—H19B	0.9600
C8—H8	0.9800	C19—H19C	0.9600
C9—C11	1.532 (3)	C17A—O17B	1.195 (3)
C9—C10	1.546 (3)	C17A—O17A	1.340 (3)
C9—H9	0.9800	C17A—C17B	1.490 (4)
C10—C19	1.538 (3)	C17B—H17B	0.9600
C11—C12	1.531 (3)	C17B—H17C	0.9600
C11—H11A	0.9700	C17B—H17D	0.9600
C2—C1—C10	113.4 (2)	H11A—C11—H11B	107.7
C2—C1—H1A	108.9	C13—C12—C11	111.2 (2)
C10—C1—H1A	108.9	C13—C12—H12A	109.4
C2—C1—H1B	108.9	C11—C12—H12A	109.4
C10—C1—H1B	108.9	C13—C12—H12B	109.4
H1A—C1—H1B	107.7	C11—C12—H12B	109.4
C3—C2—C1	113.2 (2)	H12A—C12—H12B	108.0
C3—C2—H2A	108.9	C17—C13—C12	115.5 (2)
C1—C2—H2A	108.9	C17—C13—C18	110.66 (18)
C3—C2—H2B	108.9	C12—C13—C18	111.13 (19)
C1—C2—H2B	108.9	C17—C13—C14	98.27 (17)
H2A—C2—H2B	107.7	C12—C13—C14	107.64 (17)
C4—C3—C2	122.6 (3)	C18—C13—C14	113.1 (2)
C4—C3—H3	118.7	C8—C14—C13	114.43 (17)
C2—C3—H3	118.7	C8—C14—C15	119.4 (2)
C3—C4—C5	123.6 (3)	C13—C14—C15	103.75 (18)
C3—C4—H4	118.2	C8—C14—H14	106.1
C5—C4—H4	118.2	C13—C14—H14	106.1
C4—C5—C6	114.0 (2)	C15—C14—H14	106.1
C4—C5—C10	112.18 (18)	C14—C15—C16	103.8 (2)
C6—C5—C10	112.93 (18)	C14—C15—H15A	111.0
C4—C5—H5	105.6	C16—C15—H15A	111.0
C6—C5—H5	105.6	C14—C15—H15B	111.0
C10—C5—H5	105.6	C16—C15—H15B	111.0
C7—C6—C5	110.3 (2)	H15A—C15—H15B	109.0
C7—C6—H6A	109.6	C17—C16—C15	105.17 (18)
C5—C6—H6A	109.6	C17—C16—H16A	110.7
C7—C6—H6B	109.6	C15—C16—H16A	110.7
C5—C6—H6B	109.6	C17—C16—H16B	110.7
H6A—C6—H6B	108.1	C15—C16—H16B	110.7
C6—C7—C8	112.61 (19)	H16A—C16—H16B	108.8
C6—C7—H7A	109.1	O17A—C17—C13	111.19 (17)
C8—C7—H7A	109.1	O17A—C17—C16	113.30 (19)
C6—C7—H7B	109.1	C13—C17—C16	104.5 (2)
C8—C7—H7B	109.1	O17A—C17—H17	109.2
H7A—C7—H7B	107.8	C13—C17—H17	109.2
C14—C8—C7	111.78 (18)	C16—C17—H17	109.2
C14—C8—C9	108.42 (18)	C13—C18—H18A	109.5
C7—C8—C9	111.75 (17)	C13—C18—H18B	109.5
C14—C8—H8	108.3	H18A—C18—H18B	109.5
C7—C8—H8	108.3	C13—C18—H18C	109.5
C9—C8—H8	108.3	H18A—C18—H18C	109.5
C11—C9—C10	114.78 (17)	H18B—C18—H18C	109.5
C11—C9—C8	110.83 (16)	C10—C19—H19A	109.5
C10—C9—C8	112.44 (17)	C10—C19—H19B	109.5
C11—C9—H9	106.0	H19A—C19—H19B	109.5
C10—C9—H9	106.0	C10—C19—H19C	109.5
C8—C9—H9	106.0	H19A—C19—H19C	109.5
C1—C10—C19	108.93 (19)	H19B—C19—H19C	109.5
C1—C10—C9	111.59 (19)	O17B—C17A—O17A	123.3 (3)
C19—C10—C9	111.01 (18)	O17B—C17A—C17B	125.3 (3)
C1—C10—C5	105.87 (18)	O17A—C17A—C17B	111.4 (2)
C19—C10—C5	111.4 (2)	C17A—C17B—H17B	109.5
C9—C10—C5	107.95 (16)	C17A—C17B—H17C	109.5
C12—C11—C9	113.60 (18)	H17B—C17B—H17C	109.5
C12—C11—H11A	108.8	C17A—C17B—H17D	109.5
C9—C11—H11A	108.8	H17B—C17B—H17D	109.5
C12—C11—H11B	108.8	H17C—C17B—H17D	109.5
C9—C11—H11B	108.8	C17A—O17A—C17	116.84 (19)
C10—C1—C2—C3	−37.9 (3)	C9—C11—C12—C13	−55.1 (3)
C1—C2—C3—C4	6.9 (4)	C11—C12—C13—C17	163.78 (18)
C2—C3—C4—C5	−1.2 (5)	C11—C12—C13—C18	−69.1 (2)
C3—C4—C5—C6	155.6 (3)	C11—C12—C13—C14	55.2 (2)
C3—C4—C5—C10	25.7 (4)	C7—C8—C14—C13	−177.5 (2)
C4—C5—C6—C7	172.2 (2)	C9—C8—C14—C13	58.9 (2)
C10—C5—C6—C7	−58.2 (3)	C7—C8—C14—C15	−53.7 (3)
C5—C6—C7—C8	54.7 (3)	C9—C8—C14—C15	−177.28 (19)
C6—C7—C8—C14	−174.4 (2)	C17—C13—C14—C8	179.97 (19)
C6—C7—C8—C9	−52.7 (3)	C12—C13—C14—C8	−59.9 (2)
C14—C8—C9—C11	−53.2 (2)	C18—C13—C14—C8	63.3 (2)
C7—C8—C9—C11	−176.8 (2)	C17—C13—C14—C15	48.1 (2)
C14—C8—C9—C10	176.82 (17)	C12—C13—C14—C15	168.3 (2)
C7—C8—C9—C10	53.2 (2)	C18—C13—C14—C15	−68.6 (2)
C2—C1—C10—C19	−60.0 (3)	C8—C14—C15—C16	−162.0 (2)
C2—C1—C10—C9	177.1 (2)	C13—C14—C15—C16	−33.2 (2)
C2—C1—C10—C5	59.9 (3)	C14—C15—C16—C17	4.6 (3)
C11—C9—C10—C1	61.9 (2)	C12—C13—C17—O17A	78.3 (3)
C8—C9—C10—C1	−170.18 (18)	C18—C13—C17—O17A	−49.0 (3)
C11—C9—C10—C19	−59.8 (3)	C14—C13—C17—O17A	−167.57 (19)
C8—C9—C10—C19	68.1 (2)	C12—C13—C17—C16	−159.1 (2)
C11—C9—C10—C5	177.85 (19)	C18—C13—C17—C16	73.6 (2)
C8—C9—C10—C5	−54.2 (2)	C14—C13—C17—C16	−45.0 (2)
C4—C5—C10—C1	−52.5 (3)	C15—C16—C17—O17A	146.8 (2)
C6—C5—C10—C1	177.1 (2)	C15—C16—C17—C13	25.6 (3)
C4—C5—C10—C19	65.8 (3)	O17B—C17A—O17A—C17	−0.1 (4)
C6—C5—C10—C19	−64.7 (2)	C17B—C17A—O17A—C17	179.8 (2)
C4—C5—C10—C9	−172.1 (2)	C13—C17—O17A—C17A	−164.9 (2)
C6—C5—C10—C9	57.5 (2)	C16—C17—O17A—C17A	77.7 (3)
C10—C9—C11—C12	−177.70 (18)	C19—C10—C13—C18	3.33 (19)
C8—C9—C11—C12	53.6 (2)