N-tert-Butyl-5α-androstane-17β-carboxamide

Yan, X.; Xu, S.; Wang, J.; Chen, Y.; Xia, P.

doi:10.1107/S1600536809005741

organic compounds

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ISSN: 2056-9890

Volume 65| Part 3| March 2009| Page o587

doi:10.1107/S1600536809005741

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N-tert-Butyl-5α-androstane-17β-carboxamide

Xin Yan,^a Shiqing Xu,^a Jingmei Wang,^b Ying Chen ^a and Peng Xia ^a ^*

^aDepartment of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 200032, People's Republic of China, and ^bCenter of Analysis and Measurement, Fudan University, Shanghai 200433, People's Republic of China
^*Correspondence e-mail: pxia@fudan.edu.cn

(Received 10 February 2009; accepted 18 February 2009; online 25 February 2009)

The title compound, C₂₄H₄₁NO, is a new derivative of the anti-HIV steroid 17β-(N-tert-butylaminocarbonyl)androst-4-en-3-one. There are four rings in the structure and these are trans-fused. The three six-membered rings exhibit chair conformations, while the five-membered ring adopts an envelope conformation.

Related literature

For the anti-HIV activity of 17β-(N-tert-butylaminocarbonyl)-androst-4-en-3-one, see: Xia et al. (1999 ). For discussion of absolute configuration, see: Marker et al. (1940 ); Fieser & Fieser (1959 ); Throop & Tokes (1967 ); House (1972 ); Castro-Méndez et al. (2002 ).

Experimental

Crystal data

C₂₄H₄₁NO
M_r = 359.58
Orthorhombic, P 2₁ 2₁ 2₁
a = 6.373 (2) Å
b = 12.802 (4) Å
c = 26.775 (9) Å
V = 2184.3 (12) Å³
Z = 4
Mo Kα radiation
μ = 0.07 mm⁻¹
T = 294 K
0.15 × 0.08 × 0.06 mm

Data collection

Bruker SMART CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ) T_min = 0.990, T_max = 0.996
10583 measured reflections
2757 independent reflections
1433 reflections with I > 2σ(I)
R_int = 0.063

Refinement

R[F² > 2σ(F²)] = 0.037
wR(F²) = 0.068
S = 0.75
2757 reflections
240 parameters
H-atom parameters constrained
Δρ_max = 0.10 e Å⁻³
Δρ_min = −0.12 e Å⁻³

Data collection: SMART (Bruker, 2000 ); cell refinement: SAINT (Bruker, 2000); 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.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809005741/tk2372sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809005741/tk2372Isup2.hkl

checkCIF report

Comment top

17β-(N-tert-Butylcarboxamide)-androst-4-ene-3-one was reported to exhibit potent anti-HIV activity in acutely infected H₉ lymphocytes with EC₅₀ and therapeutic index values of 0.8 and 300 µM, respectively (Xia et al., 1999). During our work of structural modification, which is motivated by the search for more potent anti-HIV agents, we found that 17β-(N-tert-butylcarboxamide)-5α-androstane (I) could be obtained through Pd/C catalytic hydrogenation of 17β-(N-tert-butylcarboxamide)-androst-4-ene-3-ol in excellent yield (90%); full structural details of (I) are reported herein.

The molecular structure of (I), Fig.1, shows the A/B, B/C and C/D ring junctions to be all trans. The cyclohexane rings adopt chair conformations, and the cyclopentane ring adopts an envelope conformation. Based on the known configurations of the C10, C13-methyl groups, see Experimental, 5-H is assigned an α-configuration. The 17-N-tert-butylcarboxamide group is in a β-configuration. The stereogenic sites of (I) exhibit the following chirality: C5 = R, C8 = R, C9 = S, C10 = S, C13 = S, C14 = S and C17 = S.

Related literature top

For the anti-HIV activity of 17β-(N-tert-butylaminocarbonyl)-androst-4-en-3-one, see: Xia et al. (1999). For discussion of absolute configuration, see: Marker et al. (1940); Fieser & Fieser (1959); Throop & Tokes (1967); House (1972); Castro-Méndez et al. (2002);

Experimental top

Compound (I) was prepared from the corresponding 4-ene-3-ol by catalytic hydrogenation with 5% palladium-on-charcoal in EtOH for 1 day. After filtration and removal of the solvent, the residue was crystallized from acetone to give colourless crystals.

The starting material, 17β-(N-tert-butylcarboxamide)-androst-4-ene-3-ol, was obtained from the reduction of 17β-(N-tert-butylcarboxamide)-androst-4-ene-3-one with NaBH₄. It is an intermediate in the synthesis of Finasteride and derived initially from diosgenin, for which the absolute configurations of all chiral centers of the steroid skeleton have been determined (Fieser & Fieser, 1959; Marker et al., 1940). Recently, the absolute configurations of the chiral centres were confirmed by the X-ray crystal structure determination of a 3-Br substituted steroid substrate synthesized from diosgenin (Castro-Méndez et al., 2002). The hydrogenation of 4-en-3-one moiety did not cause inversion of the configurations at C8, C9, C10, C13 and C14 (Throop & Tokes, 1967; House, 1972). Thus, by comparing the orientation of 5-H to that of methyl groups at C10 and C13, the absolute configuration of (I) could be determined.

Computing details top

Data collection: SMART (Bruker, 2000); cell refinement: SMART (Bruker, 2000); data reduction: SHELXTL (Sheldrick, 2008); 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 (Sheldrick, 2008).

Figures top

Fig. 1. The molecular structure of (I), with atom labels and 30% probability displacement ellipsoids for non-H atoms.

N-tert-Butyl-5α-androstane-17β-carboxamide top

Crystal data top

C₂₄H₄₁NO	D_x = 1.093 Mg m⁻³
M_r = 359.58	Melting point: 451.5 K
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 962 reflections
a = 6.373 (2) Å	θ = 2.8–19.0°
b = 12.802 (4) Å	µ = 0.07 mm⁻¹
c = 26.775 (9) Å	T = 294 K
V = 2184.3 (12) Å³	Parallelepiped, colourless
Z = 4	0.15 × 0.08 × 0.06 mm
F(000) = 800

Data collection top

Bruker SMART CCD area-detector diffractometer	2757 independent reflections
Radiation source: sealed tube	1433 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.063
ϕ and ω scans	θ_max = 27.1°, θ_min = 1.5°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −8→8
T_min = 0.990, T_max = 0.996	k = −16→16
10583 measured reflections	l = −34→22

Refinement top

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)] = 0.037	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.068	H-atom parameters constrained
S = 0.75	w = 1/[σ²(F_o²) + (0.0299P)²] where P = (F_o² + 2F_c²)/3
2757 reflections	(Δ/σ)_max < 0.001
240 parameters	Δρ_max = 0.10 e Å⁻³
0 restraints	Δρ_min = −0.12 e Å⁻³

Crystal data top

C₂₄H₄₁NO	V = 2184.3 (12) Å³
M_r = 359.58	Z = 4
Orthorhombic, P2₁2₁2₁	Mo Kα radiation
a = 6.373 (2) Å	µ = 0.07 mm⁻¹
b = 12.802 (4) Å	T = 294 K
c = 26.775 (9) Å	0.15 × 0.08 × 0.06 mm

Data collection top

Bruker SMART CCD area-detector diffractometer	2757 independent reflections
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	1433 reflections with I > 2σ(I)
T_min = 0.990, T_max = 0.996	R_int = 0.063
10583 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.037	0 restraints
wR(F²) = 0.068	H-atom parameters constrained
S = 0.75	Δρ_max = 0.10 e Å⁻³
2757 reflections	Δρ_min = −0.12 e Å⁻³
240 parameters

Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
N1	0.8035 (3)	0.65842 (13)	0.56653 (6)	0.0540 (5)
H1	0.9247	0.6820	0.5751	0.065*
O1	0.4554 (3)	0.67334 (13)	0.58044 (5)	0.0666 (5)
C1	1.1936 (4)	0.62769 (17)	0.84810 (7)	0.0534 (6)
H1A	1.2184	0.5667	0.8274	0.064*
H1B	1.2916	0.6815	0.8377	0.064*
C2	1.2381 (4)	0.59935 (18)	0.90230 (7)	0.0614 (7)
H2A	1.1548	0.5388	0.9114	0.074*
H2B	1.3849	0.5806	0.9057	0.074*
C3	1.1892 (4)	0.6872 (2)	0.93761 (8)	0.0682 (7)
H3A	1.2928	0.7420	0.9334	0.082*
H3B	1.1993	0.6618	0.9717	0.082*
C4	0.9727 (4)	0.73240 (19)	0.92929 (7)	0.0635 (7)
H4A	0.9568	0.7949	0.9494	0.076*
H4B	0.8681	0.6822	0.9402	0.076*
C5	0.9344 (4)	0.75945 (17)	0.87460 (7)	0.0522 (6)
H5	1.0430	0.8106	0.8660	0.063*
C6	0.7298 (4)	0.81485 (17)	0.86688 (7)	0.0610 (7)
H6A	0.7239	0.8752	0.8887	0.073*
H6B	0.6157	0.7685	0.8760	0.073*
C7	0.7000 (4)	0.85044 (16)	0.81299 (7)	0.0614 (7)
H7A	0.5601	0.8792	0.8091	0.074*
H7B	0.8002	0.9053	0.8055	0.074*
C8	0.7295 (3)	0.76086 (15)	0.77615 (7)	0.0426 (5)
H8	0.6196	0.7091	0.7826	0.051*
C9	0.9436 (3)	0.70738 (15)	0.78447 (6)	0.0397 (5)
H9	1.0496	0.7621	0.7802	0.048*
C10	0.9693 (3)	0.66681 (15)	0.83881 (7)	0.0400 (5)
C11	0.9900 (4)	0.62511 (16)	0.74440 (7)	0.0508 (6)
H11A	0.9022	0.5646	0.7505	0.061*
H11B	1.1350	0.6031	0.7477	0.061*
C12	0.9537 (3)	0.66238 (17)	0.69070 (7)	0.0499 (6)
H12A	1.0565	0.7154	0.6823	0.060*
H12B	0.9722	0.6042	0.6679	0.060*
C13	0.7344 (3)	0.70711 (14)	0.68449 (7)	0.0382 (5)
C14	0.7092 (3)	0.79588 (15)	0.72231 (7)	0.0436 (5)
H14	0.8250	0.8446	0.7162	0.052*
C15	0.5092 (4)	0.85175 (17)	0.70618 (7)	0.0567 (6)
H15A	0.5117	0.9245	0.7163	0.068*
H15B	0.3863	0.8185	0.7205	0.068*
C16	0.5093 (4)	0.84178 (16)	0.64878 (7)	0.0599 (7)
H16A	0.5323	0.9095	0.6334	0.072*
H16B	0.3760	0.8145	0.6372	0.072*
C17	0.6889 (4)	0.76619 (14)	0.63516 (6)	0.0442 (6)
H17	0.8130	0.8077	0.6266	0.053*
C18	0.5691 (4)	0.62057 (15)	0.69106 (7)	0.0539 (6)
H18A	0.5990	0.5642	0.6685	0.081*
H18B	0.4323	0.6483	0.6840	0.081*
H18C	0.5730	0.5952	0.7248	0.081*
C19	0.8159 (4)	0.57727 (15)	0.84878 (8)	0.0584 (7)
H19A	0.8546	0.5178	0.8290	0.088*
H19B	0.6764	0.5989	0.8401	0.088*
H19C	0.8204	0.5589	0.8835	0.088*
C20	0.6366 (4)	0.69668 (16)	0.59120 (8)	0.0487 (6)
C21	0.7988 (4)	0.58025 (17)	0.52642 (8)	0.0598 (7)
C22	0.6959 (5)	0.48089 (17)	0.54580 (9)	0.0912 (9)
H22A	0.7737	0.4550	0.5739	0.137*
H22B	0.6947	0.4292	0.5198	0.137*
H22C	0.5545	0.4959	0.5559	0.137*
C23	1.0254 (5)	0.5606 (2)	0.51203 (10)	0.1023 (10)
H23A	1.0853	0.6236	0.4988	0.153*
H23B	1.0314	0.5066	0.4872	0.153*
H23C	1.1031	0.5392	0.5410	0.153*
C24	0.6785 (5)	0.6221 (2)	0.48153 (8)	0.0816 (8)
H24A	0.5353	0.6348	0.4908	0.122*
H24B	0.6828	0.5717	0.4550	0.122*
H24C	0.7415	0.6861	0.4705	0.122*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.0549 (14)	0.0628 (12)	0.0443 (11)	−0.0034 (11)	0.0022 (10)	−0.0105 (10)
O1	0.0572 (12)	0.0831 (11)	0.0595 (10)	−0.0006 (11)	−0.0099 (9)	−0.0130 (9)
C1	0.0520 (16)	0.0652 (14)	0.0430 (13)	0.0011 (13)	−0.0016 (12)	−0.0034 (11)
C2	0.0565 (18)	0.0790 (15)	0.0486 (14)	0.0058 (14)	−0.0050 (12)	0.0054 (13)
C3	0.075 (2)	0.0871 (18)	0.0425 (14)	0.0031 (17)	−0.0089 (14)	0.0036 (13)
C4	0.072 (2)	0.0781 (17)	0.0407 (14)	0.0077 (16)	0.0017 (13)	−0.0055 (12)
C5	0.0539 (17)	0.0644 (15)	0.0382 (13)	0.0022 (14)	0.0015 (12)	−0.0031 (11)
C6	0.069 (2)	0.0696 (15)	0.0443 (14)	0.0139 (14)	−0.0002 (12)	−0.0153 (12)
C7	0.0739 (18)	0.0619 (14)	0.0483 (14)	0.0217 (14)	0.0024 (13)	−0.0083 (12)
C8	0.0440 (15)	0.0451 (12)	0.0386 (12)	0.0060 (11)	0.0060 (10)	−0.0030 (10)
C9	0.0386 (13)	0.0454 (12)	0.0351 (12)	−0.0033 (11)	0.0036 (10)	−0.0027 (10)
C10	0.0367 (14)	0.0471 (12)	0.0363 (12)	−0.0011 (11)	0.0051 (10)	0.0010 (10)
C11	0.0466 (15)	0.0642 (14)	0.0415 (12)	0.0151 (12)	−0.0001 (11)	−0.0012 (11)
C12	0.0482 (15)	0.0620 (14)	0.0395 (12)	0.0051 (13)	0.0042 (11)	−0.0075 (11)
C13	0.0392 (14)	0.0419 (11)	0.0336 (11)	0.0017 (11)	0.0008 (10)	−0.0009 (10)
C14	0.0486 (15)	0.0413 (11)	0.0409 (12)	0.0021 (12)	0.0023 (11)	0.0032 (10)
C15	0.0699 (19)	0.0552 (14)	0.0451 (13)	0.0215 (14)	−0.0044 (12)	−0.0012 (11)
C16	0.0740 (19)	0.0529 (13)	0.0527 (14)	0.0134 (14)	−0.0027 (13)	0.0028 (12)
C17	0.0508 (15)	0.0464 (12)	0.0355 (12)	−0.0004 (12)	−0.0007 (11)	0.0017 (10)
C18	0.0607 (16)	0.0527 (13)	0.0485 (14)	−0.0046 (13)	0.0004 (12)	0.0035 (11)
C19	0.0584 (18)	0.0646 (15)	0.0522 (14)	−0.0089 (14)	−0.0024 (13)	0.0098 (12)
C20	0.0608 (18)	0.0484 (13)	0.0370 (13)	0.0006 (14)	0.0000 (13)	0.0067 (11)
C21	0.073 (2)	0.0573 (14)	0.0492 (14)	0.0029 (14)	0.0018 (13)	−0.0104 (13)
C22	0.135 (3)	0.0530 (15)	0.0855 (19)	−0.0078 (19)	0.0009 (19)	−0.0047 (14)
C23	0.085 (2)	0.124 (2)	0.098 (2)	0.017 (2)	0.016 (2)	−0.0481 (19)
C24	0.113 (2)	0.0870 (17)	0.0447 (14)	−0.0078 (18)	−0.0044 (16)	−0.0127 (14)

Geometric parameters (Å, º) top

N1—C20	1.345 (3)	C11—H11B	0.9700
N1—C21	1.468 (3)	C12—C13	1.519 (3)
N1—H1	0.8600	C12—H12A	0.9700
O1—C20	1.227 (3)	C12—H12B	0.9700
C1—C2	1.522 (3)	C13—C14	1.531 (3)
C1—C10	1.535 (3)	C13—C18	1.539 (3)
C1—H1A	0.9700	C13—C17	1.549 (3)
C1—H1B	0.9700	C14—C15	1.524 (3)
C2—C3	1.502 (3)	C14—H14	0.9800
C2—H2A	0.9700	C15—C16	1.542 (2)
C2—H2B	0.9700	C15—H15A	0.9700
C3—C4	1.513 (3)	C15—H15B	0.9700
C3—H3A	0.9700	C16—C17	1.542 (3)
C3—H3B	0.9700	C16—H16A	0.9700
C4—C5	1.524 (3)	C16—H16B	0.9700
C4—H4A	0.9700	C17—C20	1.513 (3)
C4—H4B	0.9700	C17—H17	0.9800
C5—C6	1.498 (3)	C18—H18A	0.9599
C5—C10	1.541 (3)	C18—H18B	0.9599
C5—H5	0.9800	C18—H18C	0.9599
C6—C7	1.525 (2)	C19—H19A	0.9599
C6—H6A	0.9700	C19—H19B	0.9599
C6—H6B	0.9700	C19—H19C	0.9599
C7—C8	1.524 (2)	C21—C23	1.516 (4)
C7—H7A	0.9700	C21—C24	1.523 (3)
C7—H7B	0.9700	C21—C22	1.522 (3)
C8—C14	1.515 (2)	C22—H22A	0.9599
C8—C9	1.542 (3)	C22—H22B	0.9599
C8—H8	0.9800	C22—H22C	0.9599
C9—C11	1.532 (2)	C23—H23A	0.9599
C9—C10	1.554 (2)	C23—H23B	0.9599
C9—H9	0.9800	C23—H23C	0.9599
C10—C19	1.530 (3)	C24—H24A	0.9599
C11—C12	1.532 (3)	C24—H24B	0.9599
C11—H11A	0.9700	C24—H24C	0.9599

C20—N1—C21	126.2 (2)	C13—C12—H12B	109.4
C20—N1—H1	116.9	C11—C12—H12B	109.4
C21—N1—H1	116.9	H12A—C12—H12B	108.0
C2—C1—C10	113.91 (17)	C12—C13—C14	107.69 (17)
C2—C1—H1A	108.8	C12—C13—C18	110.23 (17)
C10—C1—H1A	108.8	C14—C13—C18	112.79 (16)
C2—C1—H1B	108.8	C12—C13—C17	116.70 (16)
C10—C1—H1B	108.8	C14—C13—C17	100.48 (14)
H1A—C1—H1B	107.7	C18—C13—C17	108.70 (17)
C3—C2—C1	112.51 (19)	C8—C14—C15	118.68 (17)
C3—C2—H2A	109.1	C8—C14—C13	113.62 (16)
C1—C2—H2A	109.1	C15—C14—C13	104.39 (16)
C3—C2—H2B	109.1	C8—C14—H14	106.5
C1—C2—H2B	109.1	C15—C14—H14	106.5
H2A—C2—H2B	107.8	C13—C14—H14	106.5
C2—C3—C4	112.5 (2)	C14—C15—C16	104.07 (17)
C2—C3—H3A	109.1	C14—C15—H15A	110.9
C4—C3—H3A	109.1	C16—C15—H15A	110.9
C2—C3—H3B	109.1	C14—C15—H15B	110.9
C4—C3—H3B	109.1	C16—C15—H15B	110.9
H3A—C3—H3B	107.8	H15A—C15—H15B	109.0
C3—C4—C5	111.98 (19)	C15—C16—C17	106.73 (16)
C3—C4—H4A	109.2	C15—C16—H16A	110.4
C5—C4—H4A	109.2	C17—C16—H16A	110.4
C3—C4—H4B	109.2	C15—C16—H16B	110.4
C5—C4—H4B	109.2	C17—C16—H16B	110.4
H4A—C4—H4B	107.9	H16A—C16—H16B	108.6
C6—C5—C4	112.29 (18)	C20—C17—C16	112.92 (19)
C6—C5—C10	113.84 (17)	C20—C17—C13	114.68 (16)
C4—C5—C10	113.54 (18)	C16—C17—C13	104.10 (15)
C6—C5—H5	105.4	C20—C17—H17	108.3
C4—C5—H5	105.4	C16—C17—H17	108.3
C10—C5—H5	105.4	C13—C17—H17	108.3
C5—C6—C7	112.36 (18)	C13—C18—H18A	109.5
C5—C6—H6A	109.1	C13—C18—H18B	109.5
C7—C6—H6A	109.1	H18A—C18—H18B	109.5
C5—C6—H6B	109.1	C13—C18—H18C	109.5
C7—C6—H6B	109.1	H18A—C18—H18C	109.5
H6A—C6—H6B	107.9	H18B—C18—H18C	109.5
C8—C7—C6	111.84 (16)	C10—C19—H19A	109.5
C8—C7—H7A	109.2	C10—C19—H19B	109.5
C6—C7—H7A	109.2	H19A—C19—H19B	109.5
C8—C7—H7B	109.2	C10—C19—H19C	109.5
C6—C7—H7B	109.2	H19A—C19—H19C	109.5
H7A—C7—H7B	107.9	H19B—C19—H19C	109.5
C14—C8—C7	112.48 (16)	O1—C20—N1	122.7 (2)
C14—C8—C9	110.13 (16)	O1—C20—C17	122.2 (2)
C7—C8—C9	110.47 (17)	N1—C20—C17	115.0 (2)
C14—C8—H8	107.9	N1—C21—C23	106.2 (2)
C7—C8—H8	107.9	N1—C21—C24	110.37 (18)
C9—C8—H8	107.9	C23—C21—C24	109.7 (2)
C11—C9—C8	112.02 (16)	N1—C21—C22	109.20 (18)
C11—C9—C10	113.93 (16)	C23—C21—C22	111.0 (2)
C8—C9—C10	112.15 (15)	C24—C21—C22	110.2 (2)
C11—C9—H9	106.0	C21—C22—H22A	109.5
C8—C9—H9	106.0	C21—C22—H22B	109.5
C10—C9—H9	106.0	H22A—C22—H22B	109.5
C19—C10—C1	108.81 (17)	C21—C22—H22C	109.5
C19—C10—C5	112.08 (16)	H22A—C22—H22C	109.5
C1—C10—C5	106.56 (16)	H22B—C22—H22C	109.5
C19—C10—C9	110.26 (16)	C21—C23—H23A	109.5
C1—C10—C9	111.04 (15)	C21—C23—H23B	109.5
C5—C10—C9	108.05 (15)	H23A—C23—H23B	109.5
C9—C11—C12	114.43 (17)	C21—C23—H23C	109.5
C9—C11—H11A	108.7	H23A—C23—H23C	109.5
C12—C11—H11A	108.7	H23B—C23—H23C	109.5
C9—C11—H11B	108.7	C21—C24—H24A	109.5
C12—C11—H11B	108.7	C21—C24—H24B	109.5
H11A—C11—H11B	107.6	H24A—C24—H24B	109.5
C13—C12—C11	111.04 (16)	C21—C24—H24C	109.5
C13—C12—H12A	109.4	H24A—C24—H24C	109.5
C11—C12—H12A	109.4	H24B—C24—H24C	109.5

C10—C1—C2—C3	−54.5 (3)	C11—C12—C13—C18	−66.3 (2)
C1—C2—C3—C4	50.1 (3)	C11—C12—C13—C17	169.09 (17)
C2—C3—C4—C5	−50.5 (3)	C7—C8—C14—C15	−55.7 (3)
C3—C4—C5—C6	−173.8 (2)	C9—C8—C14—C15	−179.44 (17)
C3—C4—C5—C10	55.3 (3)	C7—C8—C14—C13	−179.00 (18)
C4—C5—C6—C7	175.0 (2)	C9—C8—C14—C13	57.3 (2)
C10—C5—C6—C7	−54.3 (2)	C12—C13—C14—C8	−61.5 (2)
C5—C6—C7—C8	53.1 (3)	C18—C13—C14—C8	60.3 (2)
C6—C7—C8—C14	−177.64 (18)	C17—C13—C14—C8	175.87 (17)
C6—C7—C8—C9	−54.1 (2)	C12—C13—C14—C15	167.69 (17)
C14—C8—C9—C11	−48.6 (2)	C18—C13—C14—C15	−70.46 (19)
C7—C8—C9—C11	−173.49 (17)	C17—C13—C14—C15	45.1 (2)
C14—C8—C9—C10	−178.19 (16)	C8—C14—C15—C16	−161.48 (18)
C7—C8—C9—C10	56.9 (2)	C13—C14—C15—C16	−33.8 (2)
C2—C1—C10—C19	−65.7 (2)	C14—C15—C16—C17	8.8 (2)
C2—C1—C10—C5	55.4 (2)	C15—C16—C17—C20	143.81 (18)
C2—C1—C10—C9	172.80 (17)	C15—C16—C17—C13	18.8 (2)
C6—C5—C10—C19	−67.1 (2)	C12—C13—C17—C20	81.4 (2)
C4—C5—C10—C19	63.0 (2)	C14—C13—C17—C20	−162.6 (2)
C6—C5—C10—C1	173.94 (18)	C18—C13—C17—C20	−44.0 (2)
C4—C5—C10—C1	−55.9 (2)	C12—C13—C17—C16	−154.74 (18)
C6—C5—C10—C9	54.5 (2)	C14—C13—C17—C16	−38.70 (19)
C4—C5—C10—C9	−175.31 (19)	C18—C13—C17—C16	79.89 (18)
C11—C9—C10—C19	−61.5 (2)	C21—N1—C20—O1	−4.2 (3)
C8—C9—C10—C19	67.1 (2)	C21—N1—C20—C17	172.60 (17)
C11—C9—C10—C1	59.2 (2)	C16—C17—C20—O1	−26.4 (3)
C8—C9—C10—C1	−172.21 (16)	C13—C17—C20—O1	92.6 (3)
C11—C9—C10—C5	175.74 (18)	C16—C17—C20—N1	156.77 (17)
C8—C9—C10—C5	−55.7 (2)	C13—C17—C20—N1	−84.2 (2)
C8—C9—C11—C12	48.2 (2)	C20—N1—C21—C23	−178.2 (2)
C10—C9—C11—C12	176.84 (18)	C20—N1—C21—C24	62.9 (3)
C9—C11—C12—C13	−53.2 (2)	C20—N1—C21—C22	−58.5 (3)
C11—C12—C13—C14	57.1 (2)

Experimental details

Crystal data
Chemical formula	C₂₄H₄₁NO
M_r	359.58
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	294
a, b, c (Å)	6.373 (2), 12.802 (4), 26.775 (9)
V (Å³)	2184.3 (12)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.07
Crystal size (mm)	0.15 × 0.08 × 0.06

Data collection
Diffractometer	Bruker SMART CCD area-detector diffractometer
Absorption correction	Multi-scan (SADABS; Sheldrick, 1996)
T_min, T_max	0.990, 0.996
No. of measured, independent and observed [I > 2σ(I)] reflections	10583, 2757, 1433
R_int	0.063
(sin θ/λ)_max (Å⁻¹)	0.641

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.037, 0.068, 0.75
No. of reflections	2757
No. of parameters	240
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.10, −0.12

Computer programs: SMART (Bruker, 2000), SHELXTL (Sheldrick, 2008), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008).

Acknowledgements

The authors acknowledge the Center of Analysis and Measurement, Fudan University, for providing research facilities.

References

Bruker (2000). SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Castro-Méndez, A., Sandoval-Ramírez, J. & Bernès, S. (2002). Acta Cryst. E58, o606–o608. Web of Science CSD CrossRef IUCr Journals Google Scholar
Fieser, L. F. & Fieser, M. (1959). Steroids, pp. 331–340. New York: Reinhold Publising Corporation. Google Scholar
House, H. O. (1972). Modern Synthetic Reactions, 2nd ed, p. 13. London: Benjamin WA. Google Scholar
Marker, R. E., Tsukamoto, T. & Turner, D. L. (1940). J. Am. Chem. Soc. 62, 2525–2532. CrossRef CAS Google Scholar
Sheldrick, G. M. (1996). SADABS. University of Göttingen, Germany. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Throop, L. J. & Tokes, L. (1967). J. Am. Chem. Soc. 89, 4789–4790. CrossRef CAS Web of Science Google Scholar
Xia, P., Yang, Z. Y., Xia, Y., Zheng, Y. Q., Cosentino, L. M. & Lee, K. H. (1999). Bioorg. Med. Chem. 7, 1907–1911. Web of Science CrossRef PubMed CAS Google Scholar