(20S,2′′S)-20-[4′-(3′′-Hydroxy-2′′-methyl­prop­yl)-3′-methylisoxazol-5-yl]-5β-preg­nan-3β,16β-diol

Hernández Linares, M.-G.; Sandoval Ramírez, J.; Meza Reyes, S.; Montiel Smith, S.; Bernès, S.

doi:10.1107/S1600536809050478

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 65| Part 12| December 2009| Pages o3265-o3266

doi:10.1107/S1600536809050478

Open

access

(20S,2′′S)-20-[4′-(3′′-Hydroxy-2′′-methylpropyl)-3′-methylisoxazol-5-yl]-5β-pregnan-3β,16β-diol

María-Guadalupe Hernández Linares,^a Jesús Sandoval Ramírez,^b Socorro Meza Reyes,^b Sara Montiel Smith ^b and Sylvain Bernès ^c ^*

^aEscuela de Ingeniería Química, Universidad del Istmo, Ciudad Universitaria s/n, 70760 Sto. Domingo Tehuantepec, Oax., Mexico, ^bFacultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, San Manuel, 72000 Puebla, Pue., Mexico, and ^cDEP Facultad de Ciencias Químicas, UANL, Guerrero y Progreso S/N, Col. Treviño, 64570 Monterrey, N.L., Mexico
^*Correspondence e-mail: sylvain_bernes@hotmail.com

(Received 4 November 2009; accepted 24 November 2009; online 28 November 2009)

The title steroidal compound, C₂₉H₄₇NO₄, was prepared in a one-pot reaction starting from a sarsasapogenin derivative of known configuration. The isoxazole heterocycle is oriented towards the α face of the steroid nucleus and, although fully functionalized on C atoms, does not provoke steric hindrance with the adjacent D ring. The absolute configuration observed for chiral centers is as expected, and shows that no epimerization occurred in the precursors. In the crystal, the three OH groups serve as donors for hydrogen bonding with O and N atoms. The isoxazole N atom is involved in O—H⋯N hydrogen bonds, forming chains along [100]. These chains are further connected via O—H⋯O and weak C—H⋯O contacts, giving rise to a three-dimensional supramolecular network.

Related literature

For a general introduction to steroids functionalized with heterocycles, see: Banday et al. (2008 ); Pathak & Jindal (1998 ); Litvinovskaya et al. (1998 ); Beam et al. (2000 ). For the biological activity of danazol, a steroid sharing structural features with the title compound, see: Gupta et al. (1999 ). For 23-acetylsarsasapogenin, used as starting material, see: Meza-Reyes et al. (2005 ).

Experimental

Crystal data

C₂₉H₄₇NO₄
M_r = 473.68
Monoclinic, P 2₁
a = 6.5540 (8) Å
b = 30.131 (4) Å
c = 7.1971 (10) Å
β = 98.500 (13)°
V = 1405.6 (3) Å³
Z = 2
Mo Kα radiation
μ = 0.07 mm⁻¹
T = 296 K
0.6 × 0.2 × 0.2 mm

Data collection

Bruker P4 diffractometer
8425 measured reflections
2534 independent reflections
2003 reflections with I > 2σ(I)
R_int = 0.030

Refinement

R[F² > 2σ(F²)] = 0.035
wR(F²) = 0.092
S = 1.07
2534 reflections
322 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.13 e Å⁻³
Δρ_min = −0.12 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O32—H32⋯O33ⁱ	0.82 (5)	1.93 (5)	2.746 (3)	170 (5)
O33—H33⋯N24ⁱⁱ	0.85 (4)	2.03 (4)	2.828 (3)	157 (4)
O34—H34⋯O32ⁱⁱⁱ	0.90 (6)	1.89 (6)	2.775 (4)	166 (5)
O33—H33⋯O23ⁱⁱ	0.85 (4)	2.69 (4)	3.536 (3)	171 (4)
C18—H18C⋯O23ⁱⁱ	0.96	2.46	3.362 (4)	157
C28—H28C⋯O34^iv	0.97	2.60	3.471 (4)	150
Symmetry codes: (i) x, y, z-1; (ii) x+1, y, z; (iii) $[-x+1, y+{\script{1\over 2}}, -z]$ ; (iv) $[-x+1, y-{\script{1\over 2}}, -z+1]$ .

Data collection: XSCANS (Siemens, 1996 ); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008) and Mercury (Macrae et al., 2006 ); software used to prepare material for publication: SHELXL97.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809050478/jj2015sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809050478/jj2015Isup2.hkl

checkCIF report

Comment top

There is a continuous interest for new synthetic routes affording steroids functionalized with heteroatoms and heterocycles, since these groups modify the biological activity of related molecules (Banday et al., 2008; Pathak & Jindal, 1998). For example, the synthesis of suitable precursors for steroids analogs to brassinosteroids has been reported (Litvinovskaya et al., 1998). Functionalization with an isoxazol heterocycle has been limited to date to few examples, where the heterocycle is fused with the A ring of the steroid. An example of a molecule belonging to this family is danazol (Gupta et al., 1999), a derivative of ethisterone, which has numerous medicinal applications.

In relation with this general goal, we have developed several reagents for the direct one-step functionalization of steroids on remote positions. The title compound was synthesized readily starting from 23-acetylsarsasapogenin (Meza-Reyes et al., 2005) in a one-pot reaction carried out in dry media (see Experimental). This new route improves known procedures, which make necessary the isolation of an oxime intermediate, prior to the heterocyclization in acid conditions (Beam et al., 2000). Full details about the involved chemistry and mechanistic aspects of this unprecedented reaction will be reported elsewhere. It was however essential to X-ray characterize the product, in order to determine if any epimerization occurred during the cleavage of rings E and F.

The title molecule displays the expected cis-fused A/B ring system, characteristic of sarsasapogenin derivatives (Fig. 1). Rings A,B and C have the expected chair conformation, while the 5-membered ring D is twisted on C13—C14. The spiroketal E/F system was cleaved during the reaction, affording a C₂₁-pregnane nucleus substituted at C20 by an isoxazol heterocycle. Positions for O and N atoms in the heterocycle were unambiguously determined from X-ray data, and are consistent with the positions for double bonds, C22=C26 and C25=N24. The isoxazol ring is oriented towards the α face, and its plane approximately bisects the mean plane of the A···D steroidal nucleus. This conformation avoids any hindrance with the methyl group, C21, and OH group at C16. The observed absolute configuration indicates that the E/F rings cleavage occurred without epimerization, despite use of the strongly acidic medium used for the reaction. C20 is retained as S, and the chiral C atom C29 in the lateral chain has the S configuration.

In the crystal, molecules are associated via O—H···N hydrogen bonds involving the isoxalic N atom as an acceptor, forming chains running along the [100] direction (Fig. 2). The hydroxyl groups at O32 and O34, form O—H···O contacts between chains. The resulting three-dimensional supramolecular network also includes weak C—H···O hydrogen bond interactions involving the O23 and O24 atoms as acceptors.

Related literature top

For a general introduction to steroids functionalized with heterocycles, see: Banday et al. (2008); Pathak & Jindal (1998); Litvinovskaya et al. (1998); Beam et al. (2000). For the biological activity of danazol, a steroid sharing structural features with the title compound, see: Gupta et al. (1999). For 23-acetylsarsasapogenin used as starting material, see: Meza-Reyes et al. (2005).

Experimental top

A mixture of 23-acetylsarsasapogenin (2 mmol), hydroxylamine hydrochloride (4 mmol) and a previously prepared P₂O₅/SiO₂ reagent (1 g) were grounded thoroughly in a mortar. An immediate color change was observed. The mortar was covered with a watch glass and put inside a microwave device (2450 MHz, 1200 W). The mixture was irradiated for 3 min, allowing the reaction to complete (TLC). The mixture was then cooled to room temperature, and 10 ml of 5% aqueous HCl was added. The resulting solution was extracted with CH₂Cl₂ (2×10 ml) and dried over CaCl₂. Evaporation of solvent under reduced pressure gave the pure title compound, in 81% yield. Anal. found (calc. for C₂₉H₄₇NO₄): C 73.52 (75.53), H 9.98 (9.99), N 2.95 (2.95%). Single crystals were obtained by slow evaporation of an acetone solution.

Computing details top

Data collection: XSCANS (Siemens, 1996); cell refinement: XSCANS (Siemens, 1996); data reduction: XSCANS (Siemens, 1996); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008) and Mercury (Macrae et al., 2006); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top

	Fig. 1. The title molecule with displacement ellipsoids for non-H atoms shown at the 30% probability level.
	Fig. 2. Packing diagram for (I) viewed down the c axis. Dashed lines indicate O—H···O and O—H···N intermolecular hydrogen bonds. Weak C—H···O intermolecular interactions have been omitted for clarity.

(20S,2''S)-20-[4'-(3''-Hydroxy-2''-methylpropyl)-3'- methylisoxazol-5-yl]-5β-pregnan-3β,16β-diol top

Crystal data top

C₂₉H₄₇NO₄	F(000) = 520
M_r = 473.68	D_x = 1.119 Mg m⁻³
Monoclinic, P2₁	Melting point: 500 K
Hall symbol: P 2yb	Mo Kα radiation, λ = 0.71073 Å
a = 6.5540 (8) Å	Cell parameters from 64 reflections
b = 30.131 (4) Å	θ = 3.7–11.9°
c = 7.1971 (10) Å	µ = 0.07 mm⁻¹
β = 98.500 (13)°	T = 296 K
V = 1405.6 (3) Å³	Needle, colorless
Z = 2	0.6 × 0.2 × 0.2 mm

Data collection top

Bruker P4 diffractometer	R_int = 0.030
Radiation source: fine-focus sealed tube	θ_max = 25.0°, θ_min = 2.7°
Graphite monochromator	h = −7→7
ω scans	k = −35→35
8425 measured reflections	l = −8→8
2534 independent reflections	3 standard reflections every 97 reflections
2003 reflections with I > 2σ(I)	intensity decay: <1%

Refinement top

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)] = 0.035	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.092	w = 1/[σ²(F_o²) + (0.041P)² + 0.1586P] where P = (F_o² + 2F_c²)/3
S = 1.07	(Δ/σ)_max < 0.001
2534 reflections	Δρ_max = 0.13 e Å⁻³
322 parameters	Δρ_min = −0.12 e Å⁻³
1 restraint	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
0 constraints	Extinction coefficient: 0.026 (2)
Primary atom site location: structure-invariant direct methods

Crystal data top

C₂₉H₄₇NO₄	V = 1405.6 (3) Å³
M_r = 473.68	Z = 2
Monoclinic, P2₁	Mo Kα radiation
a = 6.5540 (8) Å	µ = 0.07 mm⁻¹
b = 30.131 (4) Å	T = 296 K
c = 7.1971 (10) Å	0.6 × 0.2 × 0.2 mm
β = 98.500 (13)°

Data collection top

Bruker P4 diffractometer	R_int = 0.030
8425 measured reflections	3 standard reflections every 97 reflections
2534 independent reflections	intensity decay: <1%
2003 reflections with I > 2σ(I)

Refinement top

R[F² > 2σ(F²)] = 0.035	1 restraint
wR(F²) = 0.092	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	Δρ_max = 0.13 e Å⁻³
2534 reflections	Δρ_min = −0.12 e Å⁻³
322 parameters

Special details top

Experimental. Colourless crystals, m.p. 227-228°C (acetone); [α]D -106.4° (c 1.0, EtOH); IR ν max (cm-1): 3386, 3355, 3321, 2933, 2821, 1629. 1H-NMR δ: 4.12 (1H, s, H-3), 3.97 (1H, m, H-16), 3.51 and 3.47 (2H, ABX system, J3'',2'' = 6 Hz, Jgem = 11 Hz, H-3''), 3.30 (1H, dc, J20,17 = 9 Hz and J20,21 = 7 Hz, H-20), 2.47 and 2.16 (2H, dd, J1 = J2 = 8 Hz, H-1''), 2.22 (3H, s, CH3-3'), 1.28 (3H, d, J21,20 = 7 Hz, CH3-21), 0.98 (3H, s, CH3-19), 0.95 (3H, d, J = 6 Hz, CH3-2''), 0.93 (3H, s, CH3-18). 13C-NMR, δ: 10.7 (CH3-3'), 13.2 (C-18), 17.0 (C-21), 19.4 (CH3-2''), 20.9 (C-11), 24.0 (C-19), 26.1 (C-1''), 26.2 (C-7), 26.6 (C-1), 27.8 (C-12), 29.0 (C-20), 29.9 (C-2), 33.5 (C-15), 35.2 (C-6), 35.2 (C-8), 36.1 (C-9), 36.4 (C-13), 36.5 (C-5), 39.8 (C-2''), 40.4 (C-4), 42.6 (C-10), 53.9 (C-14), 58.8 (C-17), 67.0 (C-3), 67.5 (C-3''), 72.5 (C-16), 109.9 (C-5'), 159.7 (C-3', C=N), 173.0 (C-4').

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

	x	y	z	U_iso*/U_eq
C1	0.6068 (5)	0.66437 (9)	0.3655 (4)	0.0550 (8)
H1B	0.7108	0.6874	0.3689	0.066*
H1C	0.5438	0.6608	0.2357	0.066*
C2	0.4435 (5)	0.67967 (10)	0.4788 (5)	0.0647 (9)
H2A	0.3322	0.6581	0.4669	0.078*
H2B	0.3868	0.7077	0.4293	0.078*
C3	0.5310 (6)	0.68522 (11)	0.6842 (5)	0.0726 (9)
H3A	0.4185	0.6922	0.7551	0.087*
C4	0.6348 (6)	0.64271 (11)	0.7600 (5)	0.0747 (10)
H4A	0.5305	0.6199	0.7616	0.090*
H4B	0.6991	0.6476	0.8887	0.090*
C5	0.7976 (5)	0.62606 (10)	0.6460 (4)	0.0622 (8)
H5A	0.9072	0.6484	0.6565	0.075*
C6	0.8957 (7)	0.58263 (12)	0.7296 (5)	0.0806 (11)
H6B	1.0192	0.5765	0.6745	0.097*
H6C	0.9364	0.5864	0.8638	0.097*
C7	0.7507 (7)	0.54323 (11)	0.6954 (5)	0.0737 (10)
H7A	0.6348	0.5477	0.7629	0.088*
H7B	0.8227	0.5166	0.7443	0.088*
C8	0.6706 (5)	0.53673 (9)	0.4874 (4)	0.0524 (7)
H8A	0.7884	0.5303	0.4221	0.063*
C9	0.5657 (5)	0.57996 (9)	0.4041 (4)	0.0467 (6)
H9D	0.4531	0.5861	0.4760	0.056*
C10	0.7136 (4)	0.62065 (9)	0.4332 (4)	0.0504 (7)
C11	0.4650 (5)	0.57340 (9)	0.1993 (4)	0.0531 (7)
H11B	0.3837	0.5995	0.1593	0.064*
H11C	0.5729	0.5711	0.1210	0.064*
C12	0.3259 (5)	0.53243 (9)	0.1663 (4)	0.0534 (7)
H12A	0.2800	0.5290	0.0327	0.064*
H12B	0.2049	0.5368	0.2272	0.064*
C13	0.4376 (4)	0.48992 (8)	0.2428 (4)	0.0448 (6)
C14	0.5181 (5)	0.49856 (9)	0.4517 (4)	0.0519 (7)
H14C	0.3978	0.5071	0.5098	0.062*
C15	0.5816 (6)	0.45203 (10)	0.5279 (4)	0.0640 (9)
H15C	0.7132	0.4433	0.4931	0.077*
H15D	0.5907	0.4510	0.6635	0.077*
C16	0.4078 (5)	0.42238 (9)	0.4337 (4)	0.0531 (7)
H16B	0.3074	0.4196	0.5213	0.064*
C17	0.2987 (4)	0.44850 (9)	0.2579 (4)	0.0476 (7)
H17C	0.1690	0.4597	0.2923	0.057*
C18	0.6125 (5)	0.47874 (10)	0.1303 (4)	0.0528 (7)
H18A	0.7116	0.5024	0.1432	0.079*
H18B	0.5567	0.4751	0.0001	0.079*
H18C	0.6784	0.4517	0.1772	0.079*
C19	0.8950 (5)	0.61529 (13)	0.3227 (6)	0.0778 (10)
H19B	0.8434	0.6123	0.1913	0.117*
H19C	0.9725	0.5893	0.3655	0.117*
H19D	0.9827	0.6409	0.3420	0.117*
C20	0.2387 (5)	0.41917 (9)	0.0833 (4)	0.0504 (7)
H20B	0.3654	0.4067	0.0478	0.061*
C21	0.1250 (5)	0.44472 (10)	−0.0881 (5)	0.0631 (8)
H21C	0.0756	0.4241	−0.1861	0.095*
H21D	0.2184	0.4653	−0.1331	0.095*
H21E	0.0105	0.4606	−0.0515	0.095*
C22	0.1037 (4)	0.38157 (9)	0.1246 (4)	0.0499 (7)
O23	−0.0587 (3)	0.39290 (7)	0.2120 (4)	0.0703 (7)
N24	−0.1752 (4)	0.35417 (10)	0.2322 (4)	0.0703 (8)
C25	−0.0791 (5)	0.32195 (10)	0.1605 (4)	0.0538 (7)
C26	0.1011 (4)	0.33757 (9)	0.0881 (4)	0.0445 (6)
C27	−0.1567 (5)	0.27556 (11)	0.1658 (5)	0.0661 (9)
H27D	−0.2718	0.2748	0.2340	0.099*
H27E	−0.0487	0.2568	0.2268	0.099*
H27F	−0.1994	0.2652	0.0399	0.099*
C28	0.2554 (4)	0.31208 (9)	−0.0033 (4)	0.0474 (6)
H28C	0.2499	0.2812	0.0334	0.057*
H28D	0.3922	0.3231	0.0446	0.057*
C29	0.2250 (5)	0.31457 (10)	−0.2173 (4)	0.0554 (7)
H29C	0.2155	0.3459	−0.2545	0.067*
C30	0.0285 (6)	0.2913 (2)	−0.3036 (6)	0.123 (2)
H30B	0.0167	0.2925	−0.4381	0.185*
H30C	−0.0882	0.3059	−0.2641	0.185*
H30D	0.0325	0.2609	−0.2633	0.185*
C31	0.4103 (5)	0.29436 (10)	−0.2882 (4)	0.0624 (8)
H31C	0.5325	0.3107	−0.2351	0.075*
H31D	0.4266	0.2641	−0.2429	0.075*
O32	0.3985 (5)	0.29406 (8)	−0.4864 (3)	0.0788 (8)
H32	0.411 (8)	0.3187 (17)	−0.533 (7)	0.118*
O33	0.4750 (3)	0.37840 (6)	0.3970 (3)	0.0570 (6)
H33	0.584 (6)	0.3790 (14)	0.345 (5)	0.086*
O34	0.6814 (5)	0.71965 (8)	0.7127 (4)	0.0898 (9)
H34	0.633 (9)	0.743 (2)	0.640 (8)	0.135*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0655 (19)	0.0375 (15)	0.0597 (18)	−0.0086 (14)	0.0013 (15)	0.0075 (13)
C2	0.0618 (19)	0.0362 (16)	0.093 (3)	0.0006 (14)	0.0010 (18)	0.0017 (16)
C3	0.095 (3)	0.0424 (17)	0.083 (2)	0.0033 (18)	0.023 (2)	−0.0076 (16)
C4	0.121 (3)	0.0451 (18)	0.058 (2)	0.007 (2)	0.011 (2)	−0.0015 (15)
C5	0.079 (2)	0.0448 (17)	0.0573 (19)	0.0017 (15)	−0.0073 (16)	0.0000 (14)
C6	0.103 (3)	0.059 (2)	0.069 (2)	0.020 (2)	−0.025 (2)	−0.0043 (16)
C7	0.113 (3)	0.0437 (17)	0.0565 (19)	0.0123 (18)	−0.0130 (19)	0.0027 (15)
C8	0.0696 (18)	0.0367 (14)	0.0490 (15)	0.0109 (14)	0.0029 (14)	0.0027 (12)
C9	0.0567 (16)	0.0361 (14)	0.0479 (15)	0.0046 (12)	0.0099 (13)	0.0014 (11)
C10	0.0530 (16)	0.0428 (16)	0.0547 (17)	0.0034 (13)	0.0049 (13)	0.0003 (13)
C11	0.0653 (18)	0.0342 (14)	0.0564 (17)	0.0034 (13)	−0.0019 (14)	0.0071 (12)
C12	0.0599 (17)	0.0362 (14)	0.0618 (18)	0.0071 (14)	0.0009 (14)	0.0048 (13)
C13	0.0552 (16)	0.0327 (14)	0.0479 (15)	0.0084 (12)	0.0124 (13)	0.0024 (11)
C14	0.0733 (19)	0.0364 (14)	0.0471 (16)	0.0132 (13)	0.0124 (14)	0.0045 (12)
C15	0.103 (3)	0.0400 (16)	0.0488 (16)	0.0108 (17)	0.0088 (17)	0.0070 (13)
C16	0.075 (2)	0.0361 (15)	0.0540 (16)	0.0108 (14)	0.0284 (15)	0.0070 (13)
C17	0.0568 (16)	0.0341 (14)	0.0555 (16)	0.0111 (12)	0.0205 (13)	0.0027 (12)
C18	0.0611 (17)	0.0425 (15)	0.0582 (17)	0.0037 (14)	0.0198 (14)	0.0022 (13)
C19	0.064 (2)	0.083 (3)	0.090 (3)	−0.009 (2)	0.0209 (19)	−0.003 (2)
C20	0.0600 (17)	0.0341 (14)	0.0601 (17)	0.0051 (13)	0.0185 (14)	0.0018 (13)
C21	0.079 (2)	0.0459 (17)	0.0633 (19)	0.0029 (16)	0.0076 (16)	0.0018 (14)
C22	0.0503 (16)	0.0408 (15)	0.0615 (17)	0.0074 (13)	0.0175 (13)	0.0019 (13)
O23	0.0679 (14)	0.0463 (12)	0.1057 (18)	0.0066 (11)	0.0431 (13)	−0.0007 (11)
N24	0.0619 (16)	0.0570 (16)	0.099 (2)	0.0012 (14)	0.0343 (15)	0.0019 (15)
C25	0.0506 (16)	0.0491 (17)	0.0618 (18)	−0.0001 (13)	0.0082 (13)	0.0058 (14)
C26	0.0462 (15)	0.0391 (14)	0.0484 (15)	0.0026 (12)	0.0076 (12)	0.0026 (12)
C27	0.0631 (19)	0.0566 (19)	0.077 (2)	−0.0153 (16)	0.0056 (16)	0.0095 (16)
C28	0.0504 (15)	0.0388 (14)	0.0523 (16)	0.0052 (12)	0.0055 (12)	−0.0025 (12)
C29	0.0638 (18)	0.0488 (16)	0.0545 (17)	0.0065 (14)	0.0117 (14)	0.0048 (13)
C30	0.077 (2)	0.224 (7)	0.065 (2)	−0.029 (3)	0.000 (2)	−0.032 (3)
C31	0.087 (2)	0.0444 (17)	0.0610 (19)	0.0047 (16)	0.0275 (16)	0.0000 (15)
O32	0.139 (2)	0.0432 (12)	0.0641 (14)	−0.0046 (14)	0.0467 (14)	0.0002 (11)
O33	0.0660 (13)	0.0314 (10)	0.0785 (14)	0.0066 (9)	0.0266 (11)	0.0099 (10)
O34	0.128 (2)	0.0423 (13)	0.0880 (19)	−0.0053 (14)	−0.0196 (17)	−0.0085 (12)

Geometric parameters (Å, º) top

C1—C2	1.511 (5)	C16—O33	1.433 (3)
C1—C10	1.537 (4)	C16—C17	1.569 (4)
C1—H1B	0.9700	C16—H16B	0.9800
C1—H1C	0.9700	C17—C20	1.539 (4)
C2—C3	1.514 (5)	C17—H17C	0.9800
C2—H2A	0.9700	C18—H18A	0.9600
C2—H2B	0.9700	C18—H18B	0.9600
C3—O34	1.425 (4)	C18—H18C	0.9600
C3—C4	1.514 (5)	C19—H19B	0.9600
C3—H3A	0.9800	C19—H19C	0.9600
C4—C5	1.524 (5)	C19—H19D	0.9600
C4—H4A	0.9700	C20—C22	1.494 (4)
C4—H4B	0.9700	C20—C21	1.549 (4)
C5—C6	1.540 (5)	C20—H20B	0.9800
C5—C10	1.558 (4)	C21—H21C	0.9600
C5—H5A	0.9800	C21—H21D	0.9600
C6—C7	1.518 (5)	C21—H21E	0.9600
C6—H6B	0.9700	C22—C26	1.351 (4)
C6—H6C	0.9700	C22—O23	1.358 (3)
C7—C8	1.524 (4)	O23—N24	1.414 (3)
C7—H7A	0.9700	N24—C25	1.304 (4)
C7—H7B	0.9700	C25—C26	1.438 (4)
C8—C14	1.521 (4)	C25—C27	1.490 (4)
C8—C9	1.551 (4)	C26—C28	1.497 (4)
C8—H8A	0.9800	C27—H27D	0.9600
C9—C11	1.536 (4)	C27—H27E	0.9600
C9—C10	1.558 (4)	C27—H27F	0.9600
C9—H9D	0.9800	C28—C29	1.525 (4)
C10—C19	1.534 (4)	C28—H28C	0.9700
C11—C12	1.532 (4)	C28—H28D	0.9700
C11—H11B	0.9700	C29—C31	1.513 (4)
C11—H11C	0.9700	C29—C30	1.517 (5)
C12—C13	1.536 (4)	C29—H29C	0.9800
C12—H12A	0.9700	C30—H30B	0.9600
C12—H12B	0.9700	C30—H30C	0.9600
C13—C18	1.535 (4)	C30—H30D	0.9600
C13—C14	1.540 (4)	C31—O32	1.417 (4)
C13—C17	1.558 (4)	C31—H31C	0.9700
C14—C15	1.540 (4)	C31—H31D	0.9700
C14—H14C	0.9800	O32—H32	0.82 (5)
C15—C16	1.525 (5)	O33—H33	0.85 (4)
C15—H15C	0.9700	O34—H34	0.90 (6)
C15—H15D	0.9700

C2—C1—C10	114.6 (3)	C16—C15—H15C	111.1
C2—C1—H1B	108.6	C14—C15—H15C	111.1
C10—C1—H1B	108.6	C16—C15—H15D	111.1
C2—C1—H1C	108.6	C14—C15—H15D	111.1
C10—C1—H1C	108.6	H15C—C15—H15D	109.1
H1B—C1—H1C	107.6	O33—C16—C15	113.2 (3)
C1—C2—C3	111.4 (3)	O33—C16—C17	115.5 (2)
C1—C2—H2A	109.4	C15—C16—C17	106.6 (2)
C3—C2—H2A	109.4	O33—C16—H16B	107.0
C1—C2—H2B	109.4	C15—C16—H16B	107.0
C3—C2—H2B	109.4	C17—C16—H16B	107.0
H2A—C2—H2B	108.0	C20—C17—C13	119.0 (2)
O34—C3—C2	112.0 (3)	C20—C17—C16	113.6 (2)
O34—C3—C4	107.5 (3)	C13—C17—C16	104.9 (2)
C2—C3—C4	110.1 (3)	C20—C17—H17C	106.2
O34—C3—H3A	109.1	C13—C17—H17C	106.2
C2—C3—H3A	109.1	C16—C17—H17C	106.2
C4—C3—H3A	109.1	C13—C18—H18A	109.5
C3—C4—C5	113.4 (3)	C13—C18—H18B	109.5
C3—C4—H4A	108.9	H18A—C18—H18B	109.5
C5—C4—H4A	108.9	C13—C18—H18C	109.5
C3—C4—H4B	108.9	H18A—C18—H18C	109.5
C5—C4—H4B	108.9	H18B—C18—H18C	109.5
H4A—C4—H4B	107.7	C10—C19—H19B	109.5
C4—C5—C6	110.8 (3)	C10—C19—H19C	109.5
C4—C5—C10	112.9 (3)	H19B—C19—H19C	109.5
C6—C5—C10	111.2 (3)	C10—C19—H19D	109.5
C4—C5—H5A	107.2	H19B—C19—H19D	109.5
C6—C5—H5A	107.2	H19C—C19—H19D	109.5
C10—C5—H5A	107.2	C22—C20—C17	111.1 (2)
C7—C6—C5	112.7 (3)	C22—C20—C21	107.8 (2)
C7—C6—H6B	109.1	C17—C20—C21	113.6 (2)
C5—C6—H6B	109.1	C22—C20—H20B	108.1
C7—C6—H6C	109.1	C17—C20—H20B	108.1
C5—C6—H6C	109.1	C21—C20—H20B	108.1
H6B—C6—H6C	107.8	C20—C21—H21C	109.5
C6—C7—C8	112.1 (3)	C20—C21—H21D	109.5
C6—C7—H7A	109.2	H21C—C21—H21D	109.5
C8—C7—H7A	109.2	C20—C21—H21E	109.5
C6—C7—H7B	109.2	H21C—C21—H21E	109.5
C8—C7—H7B	109.2	H21D—C21—H21E	109.5
H7A—C7—H7B	107.9	C26—C22—O23	110.4 (3)
C14—C8—C7	112.7 (3)	C26—C22—C20	134.1 (3)
C14—C8—C9	109.1 (2)	O23—C22—C20	115.4 (2)
C7—C8—C9	109.9 (2)	C22—O23—N24	108.2 (2)
C14—C8—H8A	108.4	C25—N24—O23	105.9 (2)
C7—C8—H8A	108.4	N24—C25—C26	111.7 (3)
C9—C8—H8A	108.4	N24—C25—C27	120.1 (3)
C11—C9—C8	111.5 (2)	C26—C25—C27	128.1 (3)
C11—C9—C10	113.6 (2)	C22—C26—C25	103.8 (2)
C8—C9—C10	112.2 (2)	C22—C26—C28	126.8 (3)
C11—C9—H9D	106.3	C25—C26—C28	129.5 (3)
C8—C9—H9D	106.3	C25—C27—H27D	109.5
C10—C9—H9D	106.3	C25—C27—H27E	109.5
C19—C10—C1	106.1 (3)	H27D—C27—H27E	109.5
C19—C10—C5	109.4 (3)	C25—C27—H27F	109.5
C1—C10—C5	107.5 (2)	H27D—C27—H27F	109.5
C19—C10—C9	111.2 (2)	H27E—C27—H27F	109.5
C1—C10—C9	112.7 (2)	C26—C28—C29	115.0 (2)
C5—C10—C9	109.7 (2)	C26—C28—H28C	108.5
C12—C11—C9	114.4 (2)	C29—C28—H28C	108.5
C12—C11—H11B	108.7	C26—C28—H28D	108.5
C9—C11—H11B	108.7	C29—C28—H28D	108.5
C12—C11—H11C	108.7	H28C—C28—H28D	107.5
C9—C11—H11C	108.7	C31—C29—C30	110.6 (3)
H11B—C11—H11C	107.6	C31—C29—C28	109.2 (2)
C11—C12—C13	112.0 (2)	C30—C29—C28	111.5 (3)
C11—C12—H12A	109.2	C31—C29—H29C	108.5
C13—C12—H12A	109.2	C30—C29—H29C	108.5
C11—C12—H12B	109.2	C28—C29—H29C	108.5
C13—C12—H12B	109.2	C29—C30—H30B	109.5
H12A—C12—H12B	107.9	C29—C30—H30C	109.5
C18—C13—C12	110.3 (2)	H30B—C30—H30C	109.5
C18—C13—C14	112.2 (2)	C29—C30—H30D	109.5
C12—C13—C14	106.6 (2)	H30B—C30—H30D	109.5
C18—C13—C17	110.5 (2)	H30C—C30—H30D	109.5
C12—C13—C17	116.1 (2)	O32—C31—C29	114.5 (3)
C14—C13—C17	100.8 (2)	O32—C31—H31C	108.6
C8—C14—C13	114.5 (2)	C29—C31—H31C	108.6
C8—C14—C15	119.5 (3)	O32—C31—H31D	108.6
C13—C14—C15	103.3 (2)	C29—C31—H31D	108.6
C8—C14—H14C	106.2	H31C—C31—H31D	107.6
C13—C14—H14C	106.2	C31—O32—H32	114 (3)
C15—C14—H14C	106.2	C16—O33—H33	111 (3)
C16—C15—C14	103.3 (3)	C3—O34—H34	108 (4)

C10—C1—C2—C3	57.4 (3)	C18—C13—C14—C15	−71.8 (3)
C1—C2—C3—O34	64.8 (3)	C12—C13—C14—C15	167.4 (3)
C1—C2—C3—C4	−54.7 (4)	C17—C13—C14—C15	45.8 (3)
O34—C3—C4—C5	−68.1 (4)	C8—C14—C15—C16	−169.8 (2)
C2—C3—C4—C5	54.2 (4)	C13—C14—C15—C16	−41.3 (3)
C3—C4—C5—C6	−179.6 (3)	C14—C15—C16—O33	148.1 (2)
C3—C4—C5—C10	−54.1 (4)	C14—C15—C16—C17	20.0 (3)
C4—C5—C6—C7	72.2 (4)	C18—C13—C17—C20	−42.3 (3)
C10—C5—C6—C7	−54.2 (4)	C12—C13—C17—C20	84.3 (3)
C5—C6—C7—C8	55.6 (4)	C14—C13—C17—C20	−161.1 (2)
C6—C7—C8—C14	−177.6 (3)	C18—C13—C17—C16	86.1 (3)
C6—C7—C8—C9	−55.7 (4)	C12—C13—C17—C16	−147.3 (2)
C14—C8—C9—C11	−50.7 (3)	C14—C13—C17—C16	−32.7 (2)
C7—C8—C9—C11	−174.7 (3)	O33—C16—C17—C20	12.9 (3)
C14—C8—C9—C10	−179.4 (2)	C15—C16—C17—C20	139.6 (3)
C7—C8—C9—C10	56.6 (3)	O33—C16—C17—C13	−118.7 (2)
C2—C1—C10—C19	−170.8 (3)	C15—C16—C17—C13	8.0 (3)
C2—C1—C10—C5	−53.8 (3)	C13—C17—C20—C22	−179.3 (2)
C2—C1—C10—C9	67.2 (3)	C16—C17—C20—C22	56.4 (3)
C4—C5—C10—C19	166.0 (3)	C13—C17—C20—C21	−57.6 (3)
C6—C5—C10—C19	−68.8 (4)	C16—C17—C20—C21	178.2 (3)
C4—C5—C10—C1	51.2 (3)	C17—C20—C22—C26	−134.1 (3)
C6—C5—C10—C1	176.4 (3)	C21—C20—C22—C26	100.9 (4)
C4—C5—C10—C9	−71.8 (3)	C17—C20—C22—O23	48.8 (3)
C6—C5—C10—C9	53.5 (4)	C21—C20—C22—O23	−76.2 (3)
C11—C9—C10—C19	−62.0 (3)	C26—C22—O23—N24	−0.6 (3)
C8—C9—C10—C19	65.5 (3)	C20—C22—O23—N24	177.2 (2)
C11—C9—C10—C1	57.0 (3)	C22—O23—N24—C25	0.9 (3)
C8—C9—C10—C1	−175.5 (2)	O23—N24—C25—C26	−0.8 (3)
C11—C9—C10—C5	176.8 (2)	O23—N24—C25—C27	177.5 (3)
C8—C9—C10—C5	−55.7 (3)	O23—C22—C26—C25	0.1 (3)
C8—C9—C11—C12	49.7 (3)	C20—C22—C26—C25	−177.1 (3)
C10—C9—C11—C12	177.6 (2)	O23—C22—C26—C28	−178.8 (2)
C9—C11—C12—C13	−53.1 (3)	C20—C22—C26—C28	4.0 (5)
C11—C12—C13—C18	−66.6 (3)	N24—C25—C26—C22	0.5 (4)
C11—C12—C13—C14	55.4 (3)	C27—C25—C26—C22	−177.7 (3)
C11—C12—C13—C17	166.7 (2)	N24—C25—C26—C28	179.3 (3)
C7—C8—C14—C13	−178.4 (3)	C27—C25—C26—C28	1.2 (5)
C9—C8—C14—C13	59.3 (3)	C22—C26—C28—C29	−81.4 (4)
C7—C8—C14—C15	−55.2 (4)	C25—C26—C28—C29	100.0 (3)
C9—C8—C14—C15	−177.6 (3)	C26—C28—C29—C31	170.2 (2)
C18—C13—C14—C8	59.7 (3)	C26—C28—C29—C30	−67.2 (4)
C12—C13—C14—C8	−61.1 (3)	C30—C29—C31—O32	55.9 (4)
C17—C13—C14—C8	177.3 (2)	C28—C29—C31—O32	179.0 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O32—H32···O33ⁱ	0.82 (5)	1.93 (5)	2.746 (3)	170 (5)
O33—H33···N24ⁱⁱ	0.85 (4)	2.03 (4)	2.828 (3)	157 (4)
O34—H34···O32ⁱⁱⁱ	0.90 (6)	1.89 (6)	2.775 (4)	166 (5)
O33—H33···O23ⁱⁱ	0.85 (4)	2.69 (4)	3.536 (3)	171 (4)
C18—H18C···O23ⁱⁱ	0.96	2.46	3.362 (4)	157
C28—H28C···O34^iv	0.97	2.60	3.471 (4)	150

Symmetry codes: (i) x, y, z−1; (ii) x+1, y, z; (iii) −x+1, y+1/2, −z; (iv) −x+1, y−1/2, −z+1.

Experimental details

Crystal data
Chemical formula	C₂₉H₄₇NO₄
M_r	473.68
Crystal system, space group	Monoclinic, P2₁
Temperature (K)	296
a, b, c (Å)	6.5540 (8), 30.131 (4), 7.1971 (10)
β (°)	98.500 (13)
V (Å³)	1405.6 (3)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.07
Crystal size (mm)	0.6 × 0.2 × 0.2

Data collection
Diffractometer	Bruker P4 diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	8425, 2534, 2003
R_int	0.030
(sin θ/λ)_max (Å⁻¹)	0.595

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.035, 0.092, 1.07
No. of reflections	2534
No. of parameters	322
No. of restraints	1
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.13, −0.12

Computer programs: XSCANS (Siemens, 1996), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008) and Mercury (Macrae et al., 2006).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O32—H32···O33ⁱ	0.82 (5)	1.93 (5)	2.746 (3)	170 (5)
O33—H33···N24ⁱⁱ	0.85 (4)	2.03 (4)	2.828 (3)	157 (4)
O34—H34···O32ⁱⁱⁱ	0.90 (6)	1.89 (6)	2.775 (4)	166 (5)
O33—H33···O23ⁱⁱ	0.85 (4)	2.69 (4)	3.536 (3)	171 (4)
C18—H18C···O23ⁱⁱ	0.96	2.46	3.362 (4)	156.9
C28—H28C···O34^iv	0.97	2.60	3.471 (4)	150.2

Symmetry codes: (i) x, y, z−1; (ii) x+1, y, z; (iii) −x+1, y+1/2, −z; (iv) −x+1, y−1/2, −z+1.

Acknowledgements

This work was supported by Consejo Nacional de Ciencia y Tecnología (CONACyT, grant 83049).

References

Banday, A. H., Singh, S., Alam, M. S., Reddy, D. M., Gupta, B. D. & Kumar, H. M. S. (2008). Steroids, 73, 370–374. Web of Science CrossRef PubMed CAS Google Scholar
Beam, C. F., Schady, D. A., Rose, K. L., Kelley, W. Jr, Rakkhit, R., Hornsby, C. D. & Studer-Martinez, S. L. (2000). Synth. Commun. 30, 3391–3404. Web of Science CrossRef CAS Google Scholar
Gupta, R., Pathak, D. & Jindal, D. P. (1999). Eur. J. Med. Chem. 34, 659–662. Web of Science PubMed CAS Google Scholar
Litvinovskaya, R. P., Drach, S. V. & Khripach, V. A. (1998). Russ. J. Org. Chem. 34, 647–654. CAS Google Scholar
Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453–457. Web of Science CrossRef CAS IUCr Journals Google Scholar
Meza-Reyes, S., Sandoval-Ramírez, J., Montiel-Smith, S., Hernández-Linares, G., Vinãs-Bravo, O., Martínez-Pascual, R., Fernández-Herrera, M. A., Vega-Báez, J. L., Merino-Montiel, P., Santillán, R. L., et al. (2005). Arkivoc, vi, 307–320. Google Scholar
Pathak, D. & Jindal, D. P. (1998). Asian J. Chem. 10, 813–817. CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Siemens (1996). XSCANS. Siemens Analytical X-ray Instruments Inc., Madison, Wisconsin, USA. Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 65| Part 12| December 2009| Pages o3265-o3266

doi:10.1107/S1600536809050478

Open

access

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Plain Text

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Plain Text

Search IUCr Journals		doi		Advanced search
Author		volume	page

organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

(20S,2′′S)-20-[4′-(3′′-Hy­droxy-2′′-methyl­prop­yl)-3′-methylisoxazol-5-yl]-5β-preg­nan-3β,16β-diol

Related literature

Experimental

Crystal data

Data collection

Refinement

Supporting information

Acknowledgements

References

organic compounds

(20S,2′′S)-20-[4′-(3′′-Hydroxy-2′′-methylpropyl)-3′-methylisoxazol-5-yl]-5β-pregnan-3β,16β-diol