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organic compounds
6β-Acetamido-5α-hydroxycholestan-3β-yl acetate
aLaboratório de Química Farmacêutica, Faculdade de Farmácia, Universidade de Coimbra, P-3000-295 Coimbra, Portugal, and bCEMDRX, Departamento de Física, Faculdade de Ciências e Tecnologia, Universidade de Coimbra, P-3004-516 Coimbra, Portugal
*Correspondence e-mail: jap@pollux.fis.uc.pt
The title steroid, C31H53NO4, was prepared from the corresponding 5α,6α-epoxycholestane. The conformation of the six-membered rings is close to a chair form, while the five-membered ring adopts a twist conformation. The hydroxyl and acetamide groups are in axial positions. The nucleophilic species bound to the steroid nucleus at position 6 by the β-face, whereas the hydroxyl group at position 5 has α-orientation. All rings are trans-fused. The crystal packing shows that the molecules related by twofold symmetry exist as O—H⋯O hydrogen-bonded dimers.
Related literature
For epoxysteroid chemistry, see: Salvador et al. (2006, 2008
); Pinto et al. (2008a
). For the synthesis of vicinal N-acyl hydroxyamines, see: Pinto et al. (2006
). For related steroid structures, see: Pinto et al. (2007a
,b
, 2008b
). For puckering parameters, see: Cremer & Pople (1975
).
Experimental
Crystal data
|
Refinement
|
|
Data collection: SMART (Bruker, 2003); cell 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: PLATON (Spek, 2003
); software used to prepare material for publication: SHELXL97.
Supporting information
10.1107/S160053680803568X/ci2694sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: 10.1107/S160053680803568X/ci2694Isup2.hkl
The synthesis of 6β-acetamido-5α-hydroxycholestan-3β-yl acetate was efficiently accomplished by nucleophilic ring-opening of the corresponding 5α,6α-epoxycholestane catalyzed by BiBr3 in acetonitrile (Pinto et al., 2006). The product of this reaction was isolated in 90% yield and identified as the title compound from IR, 1H and 13C NMR spectroscopy data (Pinto et al., 2006). Recrystallization from acetonitrile at room temperature gave colourless single crystals suitable for X-ray diffraction analysis.
H atoms were fixed geometrically (O—H = 0.82 Å, N—H = 0.86 Å and C—H = 0.96–0.98 Å) and treated as riding with Uiso(H) = 1.2Ueq(C) and 1.5Ueq(O and methyl C). In the absence of significant
Friedel pairs were merged prior to the final Though the was not determined from the X-ray data but was known from the synthetic route.Data collection: SMART (Bruker, 2003); cell
SAINT (Bruker, 2003); data reduction: SAINT (Bruker, 2003); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008). ![]() | Fig. 1. Molecular structure of the title compound. Displacement ellipsoids are drawn at the 50% probability level. |
C31H53NO4 | F(000) = 1112 |
Mr = 503.74 | Dx = 1.091 Mg m−3 |
Monoclinic, C2 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: C 2y | Cell parameters from 5555 reflections |
a = 31.4800 (12) Å | θ = 2.4–22.9° |
b = 10.0043 (4) Å | µ = 0.07 mm−1 |
c = 9.7681 (4) Å | T = 293 K |
β = 94.276 (3)° | Truncated parallelipiped, clear colourless |
V = 3067.8 (2) Å3 | 0.40 × 0.20 × 0.14 mm |
Z = 4 |
Bruker APEXII CCD area-detector diffractometer | 4691 independent reflections |
Radiation source: fine-focus sealed tube | 2907 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.045 |
ϕ and ω scans | θmax = 30.1°, θmin = 1.3° |
Absorption correction: multi-scan (SADABS; Sheldrick, 2000) | h = −43→44 |
Tmin = 0.840, Tmax = 0.990 | k = −13→13 |
43053 measured reflections | l = −13→13 |
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)] = 0.050 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.162 | H-atom parameters constrained |
S = 1.03 | w = 1/[σ2(Fo2) + (0.0835P)2 + 0.6891P] where P = (Fo2 + 2Fc2)/3 |
4691 reflections | (Δ/σ)max = 0.001 |
333 parameters | Δρmax = 0.34 e Å−3 |
1 restraint | Δρmin = −0.24 e Å−3 |
C31H53NO4 | V = 3067.8 (2) Å3 |
Mr = 503.74 | Z = 4 |
Monoclinic, C2 | Mo Kα radiation |
a = 31.4800 (12) Å | µ = 0.07 mm−1 |
b = 10.0043 (4) Å | T = 293 K |
c = 9.7681 (4) Å | 0.40 × 0.20 × 0.14 mm |
β = 94.276 (3)° |
Bruker APEXII CCD area-detector diffractometer | 4691 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 2000) | 2907 reflections with I > 2σ(I) |
Tmin = 0.840, Tmax = 0.990 | Rint = 0.045 |
43053 measured reflections |
R[F2 > 2σ(F2)] = 0.050 | 1 restraint |
wR(F2) = 0.162 | H-atom parameters constrained |
S = 1.03 | Δρmax = 0.34 e Å−3 |
4691 reflections | Δρmin = −0.24 e Å−3 |
333 parameters |
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 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 | 0.87141 (10) | −0.0088 (3) | 0.1952 (3) | 0.0615 (8) | |
H1A | 0.8421 | −0.0361 | 0.1741 | 0.074* | |
H1B | 0.8806 | 0.0391 | 0.1163 | 0.074* | |
C2 | 0.89921 (11) | −0.1341 (3) | 0.2196 (4) | 0.0727 (9) | |
H2A | 0.8880 | −0.1876 | 0.2916 | 0.087* | |
H2B | 0.8978 | −0.1874 | 0.1365 | 0.087* | |
C3 | 0.94513 (11) | −0.0993 (4) | 0.2603 (4) | 0.0678 (9) | |
H3 | 0.9583 | −0.0598 | 0.1820 | 0.081* | |
C4 | 0.94903 (10) | −0.0042 (3) | 0.3809 (3) | 0.0592 (7) | |
H4A | 0.9786 | 0.0217 | 0.3991 | 0.071* | |
H4B | 0.9400 | −0.0490 | 0.4618 | 0.071* | |
C5 | 0.92162 (8) | 0.1215 (3) | 0.3521 (3) | 0.0484 (6) | |
C6 | 0.92943 (8) | 0.2272 (3) | 0.4659 (3) | 0.0500 (6) | |
H6 | 0.9595 | 0.2526 | 0.4664 | 0.060* | |
C7 | 0.90374 (8) | 0.3533 (3) | 0.4310 (3) | 0.0508 (6) | |
H7A | 0.9156 | 0.3976 | 0.3541 | 0.061* | |
H7B | 0.9066 | 0.4136 | 0.5089 | 0.061* | |
C8 | 0.85643 (8) | 0.3267 (3) | 0.3944 (3) | 0.0424 (5) | |
H8 | 0.8434 | 0.2971 | 0.4773 | 0.051* | |
C9 | 0.84930 (8) | 0.2180 (3) | 0.2834 (3) | 0.0443 (5) | |
H9 | 0.8610 | 0.2530 | 0.2005 | 0.053* | |
C10 | 0.87356 (8) | 0.0865 (3) | 0.3205 (3) | 0.0466 (6) | |
C11 | 0.80110 (9) | 0.1986 (3) | 0.2483 (3) | 0.0550 (7) | |
H11A | 0.7968 | 0.1321 | 0.1763 | 0.066* | |
H11B | 0.7882 | 0.1653 | 0.3287 | 0.066* | |
C12 | 0.77895 (9) | 0.3288 (3) | 0.2008 (3) | 0.0525 (7) | |
H12A | 0.7898 | 0.3571 | 0.1152 | 0.063* | |
H12B | 0.7487 | 0.3123 | 0.1836 | 0.063* | |
C13 | 0.78570 (8) | 0.4407 (3) | 0.3063 (3) | 0.0421 (6) | |
C14 | 0.83406 (8) | 0.4540 (3) | 0.3415 (3) | 0.0424 (5) | |
H14 | 0.8462 | 0.4743 | 0.2543 | 0.051* | |
C15 | 0.83868 (9) | 0.5810 (3) | 0.4253 (3) | 0.0549 (7) | |
H15A | 0.8667 | 0.6201 | 0.4198 | 0.066* | |
H15B | 0.8340 | 0.5642 | 0.5209 | 0.066* | |
C16 | 0.80370 (9) | 0.6726 (3) | 0.3580 (3) | 0.0601 (7) | |
H16A | 0.8164 | 0.7448 | 0.3089 | 0.072* | |
H16B | 0.7869 | 0.7109 | 0.4274 | 0.072* | |
C17 | 0.77525 (8) | 0.5856 (3) | 0.2575 (3) | 0.0451 (6) | |
H17 | 0.7864 | 0.5953 | 0.1670 | 0.054* | |
C18 | 0.76160 (9) | 0.4092 (3) | 0.4336 (3) | 0.0542 (7) | |
H18A | 0.7319 | 0.3972 | 0.4067 | 0.081* | |
H18B | 0.7650 | 0.4820 | 0.4976 | 0.081* | |
H18C | 0.7728 | 0.3289 | 0.4761 | 0.081* | |
C19 | 0.85347 (10) | 0.0158 (3) | 0.4394 (3) | 0.0579 (7) | |
H19A | 0.8272 | −0.0254 | 0.4058 | 0.087* | |
H19B | 0.8480 | 0.0799 | 0.5090 | 0.087* | |
H19C | 0.8727 | −0.0514 | 0.4775 | 0.087* | |
C20 | 0.72882 (8) | 0.6341 (3) | 0.2425 (3) | 0.0500 (6) | |
H20 | 0.7178 | 0.6302 | 0.3337 | 0.060* | |
C21 | 0.70059 (12) | 0.5469 (4) | 0.1483 (5) | 0.0822 (12) | |
H21A | 0.7130 | 0.5372 | 0.0621 | 0.123* | |
H21B | 0.6730 | 0.5874 | 0.1335 | 0.123* | |
H21C | 0.6978 | 0.4605 | 0.1895 | 0.123* | |
C22 | 0.72669 (9) | 0.7808 (3) | 0.1956 (3) | 0.0543 (7) | |
H22A | 0.7450 | 0.8335 | 0.2591 | 0.065* | |
H22B | 0.7380 | 0.7869 | 0.1061 | 0.065* | |
C23 | 0.68225 (10) | 0.8419 (3) | 0.1864 (4) | 0.0604 (8) | |
H23A | 0.6656 | 0.8026 | 0.1090 | 0.072* | |
H23B | 0.6685 | 0.8193 | 0.2689 | 0.072* | |
C24 | 0.68225 (10) | 0.9932 (3) | 0.1698 (3) | 0.0602 (8) | |
H24A | 0.6956 | 1.0152 | 0.0862 | 0.072* | |
H24B | 0.6996 | 1.0318 | 0.2460 | 0.072* | |
C25 | 0.63810 (11) | 1.0583 (4) | 0.1637 (4) | 0.0655 (8) | |
H25 | 0.6235 | 1.0251 | 0.2420 | 0.079* | |
C26 | 0.61094 (14) | 1.0219 (5) | 0.0335 (4) | 0.0889 (12) | |
H26A | 0.6241 | 1.0561 | −0.0449 | 0.133* | |
H26B | 0.5831 | 1.0603 | 0.0369 | 0.133* | |
H26C | 0.6085 | 0.9265 | 0.0265 | 0.133* | |
C27 | 0.64222 (15) | 1.2093 (4) | 0.1785 (5) | 0.0938 (13) | |
H27A | 0.6586 | 1.2437 | 0.1073 | 0.141* | |
H27B | 0.6563 | 1.2304 | 0.2664 | 0.141* | |
H27C | 0.6144 | 1.2491 | 0.1710 | 0.141* | |
O3A | 0.96596 (8) | −0.2259 (3) | 0.2984 (3) | 0.0831 (7) | |
C3A | 1.00685 (17) | −0.2395 (6) | 0.2845 (7) | 0.118 (2) | |
C3B | 1.0213 (2) | −0.3779 (7) | 0.3176 (9) | 0.162 (3) | |
H3BA | 1.0490 | −0.3754 | 0.3656 | 0.242* | |
H3BB | 1.0226 | −0.4279 | 0.2341 | 0.242* | |
H3BC | 1.0015 | −0.4199 | 0.3743 | 0.242* | |
O3B | 1.02871 (13) | −0.1488 (5) | 0.2544 (7) | 0.169 (2) | |
O5 | 0.93451 (6) | 0.1818 (2) | 0.2284 (2) | 0.0583 (5) | |
H5A | 0.9594 | 0.2062 | 0.2402 | 0.087* | |
N6 | 0.92306 (7) | 0.1766 (3) | 0.6033 (2) | 0.0574 (6) | |
H6A | 0.9009 | 0.1287 | 0.6138 | 0.069* | |
O6 | 0.98188 (8) | 0.2694 (4) | 0.7050 (3) | 0.0856 (8) | |
C6A | 0.94987 (10) | 0.2006 (4) | 0.7137 (3) | 0.0608 (8) | |
C6B | 0.93864 (13) | 0.1416 (6) | 0.8461 (4) | 0.0881 (12) | |
H6BA | 0.9595 | 0.0756 | 0.8757 | 0.132* | |
H6BB | 0.9111 | 0.1004 | 0.8339 | 0.132* | |
H6BC | 0.9381 | 0.2106 | 0.9142 | 0.132* |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0589 (17) | 0.0517 (17) | 0.0728 (19) | 0.0080 (14) | −0.0019 (14) | −0.0103 (15) |
C2 | 0.070 (2) | 0.0522 (18) | 0.095 (2) | 0.0131 (16) | 0.0014 (17) | −0.0149 (17) |
C3 | 0.0612 (18) | 0.0521 (17) | 0.091 (2) | 0.0156 (15) | 0.0111 (16) | 0.0011 (16) |
C4 | 0.0463 (15) | 0.0544 (17) | 0.077 (2) | 0.0114 (13) | 0.0071 (13) | 0.0047 (15) |
C5 | 0.0400 (13) | 0.0490 (14) | 0.0561 (15) | 0.0049 (11) | 0.0040 (11) | 0.0057 (12) |
C6 | 0.0358 (12) | 0.0532 (16) | 0.0604 (16) | −0.0013 (11) | 0.0005 (11) | 0.0039 (12) |
C7 | 0.0416 (13) | 0.0474 (15) | 0.0627 (16) | −0.0027 (11) | −0.0015 (11) | −0.0031 (13) |
C8 | 0.0371 (12) | 0.0432 (13) | 0.0467 (13) | −0.0005 (10) | 0.0022 (10) | −0.0014 (10) |
C9 | 0.0394 (12) | 0.0420 (13) | 0.0510 (14) | 0.0014 (10) | 0.0005 (10) | −0.0037 (10) |
C10 | 0.0399 (13) | 0.0411 (13) | 0.0582 (15) | 0.0009 (11) | 0.0008 (11) | −0.0016 (11) |
C11 | 0.0461 (14) | 0.0497 (16) | 0.0670 (17) | −0.0003 (12) | −0.0101 (12) | −0.0092 (13) |
C12 | 0.0451 (14) | 0.0510 (15) | 0.0594 (16) | 0.0052 (12) | −0.0083 (12) | −0.0098 (13) |
C13 | 0.0389 (12) | 0.0424 (13) | 0.0450 (13) | −0.0002 (10) | 0.0042 (10) | −0.0006 (10) |
C14 | 0.0412 (13) | 0.0404 (12) | 0.0453 (13) | −0.0013 (10) | 0.0022 (10) | −0.0006 (10) |
C15 | 0.0482 (15) | 0.0448 (14) | 0.0704 (18) | 0.0002 (12) | −0.0042 (13) | −0.0082 (13) |
C16 | 0.0506 (15) | 0.0471 (15) | 0.082 (2) | 0.0019 (13) | 0.0019 (14) | −0.0093 (15) |
C17 | 0.0444 (13) | 0.0452 (13) | 0.0462 (13) | 0.0028 (11) | 0.0056 (10) | 0.0035 (11) |
C18 | 0.0461 (14) | 0.0585 (16) | 0.0587 (16) | 0.0008 (13) | 0.0087 (12) | 0.0103 (13) |
C19 | 0.0488 (15) | 0.0455 (15) | 0.079 (2) | −0.0035 (12) | 0.0051 (14) | 0.0035 (14) |
C20 | 0.0467 (14) | 0.0486 (14) | 0.0546 (15) | 0.0056 (12) | 0.0024 (11) | 0.0031 (12) |
C21 | 0.063 (2) | 0.062 (2) | 0.116 (3) | 0.0088 (17) | −0.030 (2) | −0.008 (2) |
C22 | 0.0556 (15) | 0.0533 (16) | 0.0545 (15) | 0.0110 (13) | 0.0067 (12) | 0.0078 (13) |
C23 | 0.0563 (17) | 0.0579 (18) | 0.0671 (18) | 0.0147 (14) | 0.0054 (13) | 0.0103 (14) |
C24 | 0.0612 (18) | 0.0575 (18) | 0.0628 (18) | 0.0135 (14) | 0.0099 (14) | 0.0073 (14) |
C25 | 0.0664 (19) | 0.0594 (19) | 0.0717 (19) | 0.0188 (16) | 0.0113 (16) | 0.0060 (16) |
C26 | 0.084 (3) | 0.083 (3) | 0.097 (3) | 0.030 (2) | −0.008 (2) | 0.001 (2) |
C27 | 0.100 (3) | 0.064 (2) | 0.117 (3) | 0.027 (2) | 0.003 (2) | 0.000 (2) |
O3A | 0.0696 (15) | 0.0601 (14) | 0.122 (2) | 0.0235 (12) | 0.0206 (13) | 0.0056 (14) |
C3A | 0.088 (3) | 0.082 (3) | 0.191 (6) | 0.038 (3) | 0.054 (3) | 0.027 (4) |
C3B | 0.134 (5) | 0.105 (4) | 0.253 (9) | 0.077 (4) | 0.064 (5) | 0.042 (5) |
O3B | 0.091 (3) | 0.117 (4) | 0.308 (7) | 0.035 (2) | 0.077 (3) | 0.051 (4) |
O5 | 0.0489 (10) | 0.0654 (13) | 0.0616 (11) | 0.0037 (10) | 0.0108 (8) | 0.0083 (11) |
N6 | 0.0421 (12) | 0.0699 (16) | 0.0593 (13) | −0.0037 (12) | −0.0022 (10) | 0.0048 (13) |
O6 | 0.0545 (13) | 0.125 (2) | 0.0768 (15) | −0.0114 (15) | −0.0017 (11) | −0.0260 (16) |
C6A | 0.0482 (15) | 0.072 (2) | 0.0617 (17) | 0.0159 (15) | −0.0013 (13) | −0.0125 (15) |
C6B | 0.084 (2) | 0.115 (3) | 0.064 (2) | 0.013 (3) | 0.0005 (17) | −0.002 (2) |
C1—C2 | 1.537 (4) | C17—C20 | 1.536 (4) |
C1—C10 | 1.549 (4) | C17—H17 | 0.98 |
C1—H1A | 0.97 | C18—H18A | 0.96 |
C1—H1B | 0.97 | C18—H18B | 0.96 |
C2—C3 | 1.511 (5) | C18—H18C | 0.96 |
C2—H2A | 0.97 | C19—H19A | 0.96 |
C2—H2B | 0.97 | C19—H19B | 0.96 |
C3—O3A | 1.461 (4) | C19—H19C | 0.96 |
C3—C4 | 1.512 (5) | C20—C21 | 1.509 (5) |
C3—H3 | 0.98 | C20—C22 | 1.537 (4) |
C4—C5 | 1.539 (4) | C20—H20 | 0.98 |
C4—H4A | 0.97 | C21—H21A | 0.96 |
C4—H4B | 0.97 | C21—H21B | 0.96 |
C5—O5 | 1.436 (3) | C21—H21C | 0.96 |
C5—C6 | 1.541 (4) | C22—C23 | 1.523 (4) |
C5—C10 | 1.561 (4) | C22—H22A | 0.97 |
C6—N6 | 1.461 (4) | C22—H22B | 0.97 |
C6—C7 | 1.523 (4) | C23—C24 | 1.523 (5) |
C6—H6 | 0.98 | C23—H23A | 0.97 |
C7—C8 | 1.528 (4) | C23—H23B | 0.97 |
C7—H7A | 0.97 | C24—C25 | 1.532 (4) |
C7—H7B | 0.97 | C24—H24A | 0.97 |
C8—C14 | 1.527 (4) | C24—H24B | 0.97 |
C8—C9 | 1.540 (3) | C25—C27 | 1.522 (6) |
C8—H8 | 0.98 | C25—C26 | 1.522 (6) |
C9—C11 | 1.543 (4) | C25—H25 | 0.98 |
C9—C10 | 1.551 (4) | C26—H26A | 0.96 |
C9—H9 | 0.98 | C26—H26B | 0.96 |
C10—C19 | 1.535 (4) | C26—H26C | 0.96 |
C11—C12 | 1.532 (4) | C27—H27A | 0.96 |
C11—H11A | 0.97 | C27—H27B | 0.96 |
C11—H11B | 0.97 | C27—H27C | 0.96 |
C12—C13 | 1.526 (4) | O3A—C3A | 1.312 (5) |
C12—H12A | 0.97 | C3A—O3B | 1.190 (7) |
C12—H12B | 0.97 | C3A—C3B | 1.485 (7) |
C13—C18 | 1.537 (4) | C3B—H3BA | 0.96 |
C13—C14 | 1.541 (3) | C3B—H3BB | 0.96 |
C13—C17 | 1.554 (4) | C3B—H3BC | 0.96 |
C14—C15 | 1.513 (4) | O5—H5A | 0.82 |
C14—H14 | 0.98 | N6—C6A | 1.341 (4) |
C15—C16 | 1.542 (4) | N6—H6A | 0.86 |
C15—H15A | 0.97 | O6—C6A | 1.228 (4) |
C15—H15B | 0.97 | C6A—C6B | 1.488 (5) |
C16—C17 | 1.547 (4) | C6B—H6BA | 0.96 |
C16—H16A | 0.97 | C6B—H6BB | 0.96 |
C16—H16B | 0.97 | C6B—H6BC | 0.96 |
C2—C1—C10 | 112.9 (3) | C15—C16—H16B | 110.2 |
C2—C1—H1A | 109.0 | C17—C16—H16B | 110.2 |
C10—C1—H1A | 109.0 | H16A—C16—H16B | 108.5 |
C2—C1—H1B | 109.0 | C20—C17—C16 | 112.6 (2) |
C10—C1—H1B | 109.0 | C20—C17—C13 | 120.1 (2) |
H1A—C1—H1B | 107.8 | C16—C17—C13 | 103.3 (2) |
C3—C2—C1 | 112.1 (3) | C20—C17—H17 | 106.7 |
C3—C2—H2A | 109.2 | C16—C17—H17 | 106.7 |
C1—C2—H2A | 109.2 | C13—C17—H17 | 106.7 |
C3—C2—H2B | 109.2 | C13—C18—H18A | 109.5 |
C1—C2—H2B | 109.2 | C13—C18—H18B | 109.5 |
H2A—C2—H2B | 107.9 | H18A—C18—H18B | 109.5 |
O3A—C3—C2 | 105.7 (3) | C13—C18—H18C | 109.5 |
O3A—C3—C4 | 109.8 (3) | H18A—C18—H18C | 109.5 |
C2—C3—C4 | 111.7 (3) | H18B—C18—H18C | 109.5 |
O3A—C3—H3 | 109.9 | C10—C19—H19A | 109.5 |
C2—C3—H3 | 109.9 | C10—C19—H19B | 109.5 |
C4—C3—H3 | 109.9 | H19A—C19—H19B | 109.5 |
C3—C4—C5 | 111.1 (3) | C10—C19—H19C | 109.5 |
C3—C4—H4A | 109.4 | H19A—C19—H19C | 109.5 |
C5—C4—H4A | 109.4 | H19B—C19—H19C | 109.5 |
C3—C4—H4B | 109.4 | C21—C20—C17 | 112.8 (3) |
C5—C4—H4B | 109.4 | C21—C20—C22 | 111.1 (3) |
H4A—C4—H4B | 108.0 | C17—C20—C22 | 110.5 (2) |
O5—C5—C4 | 107.9 (2) | C21—C20—H20 | 107.4 |
O5—C5—C6 | 106.2 (2) | C17—C20—H20 | 107.4 |
C4—C5—C6 | 111.9 (2) | C22—C20—H20 | 107.4 |
O5—C5—C10 | 105.0 (2) | C20—C21—H21A | 109.5 |
C4—C5—C10 | 112.0 (2) | C20—C21—H21B | 109.5 |
C6—C5—C10 | 113.4 (2) | H21A—C21—H21B | 109.5 |
N6—C6—C7 | 112.7 (2) | C20—C21—H21C | 109.5 |
N6—C6—C5 | 113.5 (2) | H21A—C21—H21C | 109.5 |
C7—C6—C5 | 110.7 (2) | H21B—C21—H21C | 109.5 |
N6—C6—H6 | 106.5 | C23—C22—C20 | 114.9 (3) |
C7—C6—H6 | 106.5 | C23—C22—H22A | 108.6 |
C5—C6—H6 | 106.5 | C20—C22—H22A | 108.6 |
C6—C7—C8 | 113.6 (2) | C23—C22—H22B | 108.6 |
C6—C7—H7A | 108.9 | C20—C22—H22B | 108.6 |
C8—C7—H7A | 108.9 | H22A—C22—H22B | 107.5 |
C6—C7—H7B | 108.9 | C24—C23—C22 | 113.5 (3) |
C8—C7—H7B | 108.9 | C24—C23—H23A | 108.9 |
H7A—C7—H7B | 107.7 | C22—C23—H23A | 108.9 |
C14—C8—C7 | 110.5 (2) | C24—C23—H23B | 108.9 |
C14—C8—C9 | 108.11 (19) | C22—C23—H23B | 108.9 |
C7—C8—C9 | 112.1 (2) | H23A—C23—H23B | 107.7 |
C14—C8—H8 | 108.7 | C23—C24—C25 | 114.8 (3) |
C7—C8—H8 | 108.7 | C23—C24—H24A | 108.6 |
C9—C8—H8 | 108.7 | C25—C24—H24A | 108.6 |
C8—C9—C11 | 109.6 (2) | C23—C24—H24B | 108.6 |
C8—C9—C10 | 113.0 (2) | C25—C24—H24B | 108.6 |
C11—C9—C10 | 113.8 (2) | H24A—C24—H24B | 107.5 |
C8—C9—H9 | 106.6 | C27—C25—C26 | 110.8 (3) |
C11—C9—H9 | 106.6 | C27—C25—C24 | 110.3 (3) |
C10—C9—H9 | 106.6 | C26—C25—C24 | 112.5 (3) |
C19—C10—C1 | 108.5 (3) | C27—C25—H25 | 107.7 |
C19—C10—C9 | 110.1 (2) | C26—C25—H25 | 107.7 |
C1—C10—C9 | 110.2 (2) | C24—C25—H25 | 107.7 |
C19—C10—C5 | 113.7 (2) | C25—C26—H26A | 109.5 |
C1—C10—C5 | 106.2 (2) | C25—C26—H26B | 109.5 |
C9—C10—C5 | 108.0 (2) | H26A—C26—H26B | 109.5 |
C12—C11—C9 | 112.2 (2) | C25—C26—H26C | 109.5 |
C12—C11—H11A | 109.2 | H26A—C26—H26C | 109.5 |
C9—C11—H11A | 109.2 | H26B—C26—H26C | 109.5 |
C12—C11—H11B | 109.2 | C25—C27—H27A | 109.5 |
C9—C11—H11B | 109.2 | C25—C27—H27B | 109.5 |
H11A—C11—H11B | 107.9 | H27A—C27—H27B | 109.5 |
C13—C12—C11 | 112.4 (2) | C25—C27—H27C | 109.5 |
C13—C12—H12A | 109.1 | H27A—C27—H27C | 109.5 |
C11—C12—H12A | 109.1 | H27B—C27—H27C | 109.5 |
C13—C12—H12B | 109.1 | C3A—O3A—C3 | 119.3 (4) |
C11—C12—H12B | 109.1 | O3B—C3A—O3A | 122.4 (5) |
H12A—C12—H12B | 107.8 | O3B—C3A—C3B | 126.3 (5) |
C12—C13—C18 | 110.1 (2) | O3A—C3A—C3B | 111.2 (5) |
C12—C13—C14 | 107.4 (2) | C3A—C3B—H3BA | 109.5 |
C18—C13—C14 | 112.1 (2) | C3A—C3B—H3BB | 109.5 |
C12—C13—C17 | 117.5 (2) | H3BA—C3B—H3BB | 109.5 |
C18—C13—C17 | 109.5 (2) | C3A—C3B—H3BC | 109.5 |
C14—C13—C17 | 99.84 (19) | H3BA—C3B—H3BC | 109.5 |
C15—C14—C8 | 119.6 (2) | H3BB—C3B—H3BC | 109.5 |
C15—C14—C13 | 104.3 (2) | C5—O5—H5A | 109.5 |
C8—C14—C13 | 115.2 (2) | C6A—N6—C6 | 123.7 (3) |
C15—C14—H14 | 105.5 | C6A—N6—H6A | 118.1 |
C8—C14—H14 | 105.5 | C6—N6—H6A | 118.1 |
C13—C14—H14 | 105.5 | O6—C6A—N6 | 121.0 (3) |
C14—C15—C16 | 103.4 (2) | O6—C6A—C6B | 122.2 (3) |
C14—C15—H15A | 111.1 | N6—C6A—C6B | 116.9 (3) |
C16—C15—H15A | 111.1 | C6A—C6B—H6BA | 109.5 |
C14—C15—H15B | 111.1 | C6A—C6B—H6BB | 109.5 |
C16—C15—H15B | 111.1 | H6BA—C6B—H6BB | 109.5 |
H15A—C15—H15B | 109.1 | C6A—C6B—H6BC | 109.5 |
C15—C16—C17 | 107.3 (2) | H6BA—C6B—H6BC | 109.5 |
C15—C16—H16A | 110.2 | H6BB—C6B—H6BC | 109.5 |
C17—C16—H16A | 110.2 | ||
C10—C1—C2—C3 | −55.8 (4) | C11—C12—C13—C18 | −69.1 (3) |
C1—C2—C3—O3A | 172.3 (3) | C11—C12—C13—C14 | 53.2 (3) |
C1—C2—C3—C4 | 52.9 (4) | C11—C12—C13—C17 | 164.6 (2) |
O3A—C3—C4—C5 | −171.2 (2) | C7—C8—C14—C15 | −52.3 (3) |
C2—C3—C4—C5 | −54.3 (4) | C9—C8—C14—C15 | −175.3 (2) |
C3—C4—C5—O5 | −56.5 (3) | C7—C8—C14—C13 | −177.8 (2) |
C3—C4—C5—C6 | −172.9 (2) | C9—C8—C14—C13 | 59.2 (3) |
C3—C4—C5—C10 | 58.5 (3) | C12—C13—C14—C15 | 170.2 (2) |
O5—C5—C6—N6 | −172.7 (2) | C18—C13—C14—C15 | −68.7 (3) |
C4—C5—C6—N6 | −55.2 (3) | C17—C13—C14—C15 | 47.1 (2) |
C10—C5—C6—N6 | 72.6 (3) | C12—C13—C14—C8 | −56.7 (3) |
O5—C5—C6—C7 | 59.5 (3) | C18—C13—C14—C8 | 64.4 (3) |
C4—C5—C6—C7 | 176.9 (2) | C17—C13—C14—C8 | −179.8 (2) |
C10—C5—C6—C7 | −55.3 (3) | C8—C14—C15—C16 | −166.5 (2) |
N6—C6—C7—C8 | −76.5 (3) | C13—C14—C15—C16 | −36.0 (3) |
C5—C6—C7—C8 | 51.8 (3) | C14—C15—C16—C17 | 10.6 (3) |
C6—C7—C8—C14 | −172.1 (2) | C15—C16—C17—C20 | 149.3 (2) |
C6—C7—C8—C9 | −51.4 (3) | C15—C16—C17—C13 | 18.2 (3) |
C14—C8—C9—C11 | −56.4 (3) | C12—C13—C17—C20 | 78.9 (3) |
C7—C8—C9—C11 | −178.5 (2) | C18—C13—C17—C20 | −47.6 (3) |
C14—C8—C9—C10 | 175.5 (2) | C14—C13—C17—C20 | −165.5 (2) |
C7—C8—C9—C10 | 53.4 (3) | C12—C13—C17—C16 | −154.7 (2) |
C2—C1—C10—C19 | −66.1 (3) | C18—C13—C17—C16 | 78.8 (3) |
C2—C1—C10—C9 | 173.3 (3) | C14—C13—C17—C16 | −39.0 (2) |
C2—C1—C10—C5 | 56.5 (3) | C16—C17—C20—C21 | −178.0 (3) |
C8—C9—C10—C19 | 70.0 (3) | C13—C17—C20—C21 | −56.0 (4) |
C11—C9—C10—C19 | −55.8 (3) | C16—C17—C20—C22 | 56.9 (3) |
C8—C9—C10—C1 | −170.2 (2) | C13—C17—C20—C22 | 179.0 (2) |
C11—C9—C10—C1 | 63.9 (3) | C21—C20—C22—C23 | 57.8 (4) |
C8—C9—C10—C5 | −54.6 (3) | C17—C20—C22—C23 | −176.2 (2) |
C11—C9—C10—C5 | 179.5 (2) | C20—C22—C23—C24 | 167.7 (3) |
O5—C5—C10—C19 | 178.1 (2) | C22—C23—C24—C25 | −178.6 (3) |
C4—C5—C10—C19 | 61.3 (3) | C23—C24—C25—C27 | 167.7 (4) |
C6—C5—C10—C19 | −66.4 (3) | C23—C24—C25—C26 | −68.1 (4) |
O5—C5—C10—C1 | 58.8 (3) | C2—C3—O3A—C3A | 152.4 (5) |
C4—C5—C10—C1 | −58.0 (3) | C4—C3—O3A—C3A | −87.0 (5) |
C6—C5—C10—C1 | 174.3 (2) | C3—O3A—C3A—O3B | 7.4 (10) |
O5—C5—C10—C9 | −59.4 (3) | C3—O3A—C3A—C3B | −175.4 (5) |
C4—C5—C10—C9 | −176.2 (2) | C7—C6—N6—C6A | −98.2 (3) |
C6—C5—C10—C9 | 56.1 (3) | C5—C6—N6—C6A | 135.0 (3) |
C8—C9—C11—C12 | 57.1 (3) | C6—N6—C6A—O6 | 0.7 (5) |
C10—C9—C11—C12 | −175.3 (2) | C6—N6—C6A—C6B | 180.0 (3) |
C9—C11—C12—C13 | −56.5 (3) | C19—C10—C13—C18 | 6.3 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
O5—H5A···O6i | 0.82 | 1.99 | 2.804 (3) | 172 |
Symmetry code: (i) −x+2, y, −z+1. |
Experimental details
Crystal data | |
Chemical formula | C31H53NO4 |
Mr | 503.74 |
Crystal system, space group | Monoclinic, C2 |
Temperature (K) | 293 |
a, b, c (Å) | 31.4800 (12), 10.0043 (4), 9.7681 (4) |
β (°) | 94.276 (3) |
V (Å3) | 3067.8 (2) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.07 |
Crystal size (mm) | 0.40 × 0.20 × 0.14 |
Data collection | |
Diffractometer | Bruker APEXII CCD area-detector diffractometer |
Absorption correction | Multi-scan (SADABS; Sheldrick, 2000) |
Tmin, Tmax | 0.840, 0.990 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 43053, 4691, 2907 |
Rint | 0.045 |
(sin θ/λ)max (Å−1) | 0.706 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.050, 0.162, 1.03 |
No. of reflections | 4691 |
No. of parameters | 333 |
No. of restraints | 1 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.34, −0.24 |
Computer programs: SMART (Bruker, 2003), SAINT (Bruker, 2003), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2003).
D—H···A | D—H | H···A | D···A | D—H···A |
O5—H5A···O6i | 0.82 | 1.99 | 2.804 (3) | 172 |
Symmetry code: (i) −x+2, y, −z+1. |
Acknowledgements
This work was supported by Fundação para a Ciência e Tecnologia. RMAP thanks FCT for a grant (SFRH/BD/18013/2004).
References
Bruker (2003). SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354–1358. CrossRef CAS Web of Science Google Scholar
Pinto, R. M. A., Ramos Silva, M., Matos Beja, A. & Salvador, J. A. R. (2007b). Acta Cryst. E63, o2138–o2139. Web of Science CSD CrossRef IUCr Journals Google Scholar
Pinto, R. M. A., Ramos Silva, M., Matos Beja, A., Salvador, J. A. R. & Paixão, J. A. (2007a). Acta Cryst. E63, o3321. Web of Science CSD CrossRef IUCr Journals Google Scholar
Pinto, R. M. A., Salvador, J. A. R. & Le Roux, C. (2006). Synlett, 13, 2047–2050. Google Scholar
Pinto, R. M. A., Salvador, J. A. R. & Paixão, J. A. (2008a). Acta Cryst. C64, o279–o282. Web of Science CSD CrossRef IUCr Journals Google Scholar
Pinto, R. M. A., Salvador, J. A. R., Paixão, J. A., Matos Beja, A. & Ramos Silva, M. (2008b). Acta Cryst. E64, o1420. Web of Science CSD CrossRef IUCr Journals Google Scholar
Salvador, J. A. R., Silvestre, S. M. & Moreira, V. M. (2006). Curr. Org. Chem. 10, 2227–2257. Web of Science CrossRef CAS Google Scholar
Salvador, J. A. R., Silvestre, S. M. & Moreira, V. M. (2008). Curr. Org. Chem. 12, 492–522. Web of Science CrossRef CAS Google Scholar
Sheldrick, G. M. (2000). 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
Spek, A. L. (2003). J. Appl. Cryst. 36, 7–13. Web of Science CrossRef CAS IUCr Journals 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.
Epoxysteroids are useful synthetic intermediates in the synthesis of important biologically active molecules (Salvador et al., 2006, 2008; Pinto et al., 2008a). In fact, it is the stereochemistry of the starting epoxide that rules its nucleophilic ring-opening. Recently, using epoxides as substrates, we described an efficient one-pot procedure for the synthesis of vicinal N-acyl hydroxyamines by a bismuth(III) salt-promoted reaction (Pinto et al., 2006). Later, we reported the X-ray crystal structure of 5α-acetamido-6β-hydroxy-20-oxoandrostan-3β-yl acetate obtained by the above mentioned reaction (Pinto et al., 2007a). Since the starting epoxide has a 5β,6β-conformation, the nucleophile attacked the steroid nucleus at C5 by the α-face. The title compound has been obtained from the corresponding 5α,6α-epoxycholestane derivative, under similar reaction conditions, in 90% yield (Pinto et al., 2006). The present communication unequivocally demonstrated the trans-diaxial nature of the 5α,6α-epoxide ring-opening by the bismuth(III) salt-catalyzed Ritter reaction. Related X-ray diffraction studies on 5α-hydroxy-6β-substituted steroids have been recently published by our group (Pinto et al., 2007b, 2008b).
The conformations of the six-membered rings are close to a chair form, as shown by the Cremer & Pople (1975) puckering parameters [ring A: Q = 0.580 (3) Å, θ = 4.7 (4)° and ϕ = 276 (4)°; ring B: Q = 0.554 (3) Å, θ = 4.4 (3)° and ϕ = 318 (4)°; ring C: Q = 0.583 (3) Å, θ = 1.3 (3)° and ϕ = 20 (7)°]. The D-ring has a twisted conformation around the C13—C14 bond with puckering parameters q2 = 0.459 (3)Å and ϕ2 = 192.9 (4)°. All rings of the molecule are trans fused. The acetoxy group at C3 is equatorial to the A ring, and both substituents at ring B are axial. The amide group adopts the usual trans conformation.
The molecules are hydrogen-bonded through the hydroxyl group at C5, acting as donor towards the carbonyl O atom of the amide moiety. Remarkably, the H atom attached to the amide N atom is not involved in any hydrogen bond. This may arise from steric hindrance caused by the C19-methyl group. The following short intramolecular distances are also spotted in the structure: H1B···O5 2.42 Å, H9···O5 2.42 Å and H6···O6 2.39 Å.
The anisotropic displacement tensor of the terminal atoms of the 3β-acetoxy group are strongly anisotropic, suggesting a large amplitude of vibration of these atoms perpendicular to the mean plane of this group.