NaBH in methanol produced 3β-acetoxy-5α-androstan-17β-ol (6), base hydrolysis of which in methanol gave 5α-androstan-
4
3β,17β-diol (7) in 95% yield.
Thus, the yield of 7 starting from tigogenin was 40.8%.
EXPERIMENTAL
Melting points were determined on a Gallenkamp block. IR spectra in KBr disks were recorded on a Magna-IR
Spectrometer 550 instrument. Mass spectra were measured on a Finnigan AQA Navigator instrument (EI, 70 eV). NMR
spectra were obtained on a Bruker AM 300 instrument. Proton chemical shifts are given on the δ-scale (ppm) with TMS
internal standard and DMSO-d solvent. Elemental analyses were performed on a Perkin—Elmer CHN 2004 instrument and
6
agreed for all compounds with those calculated. The course of reactions and purity of products were monitored by TLC on
Silufol254plates(Kavalier, Czech Rep.)usingbenzene:acetone(3:1). Spots were developed byspraying with phosphomolybdic
acid (10%) in ethanol with subsequent heating.
3β-Acetoxy-5α-pregn-16-en-20-one (2). A mixture of 1 (50 g, 120.0 mmol), (CH CO) O (150 mL), and C H N
3
2
5 5
(10 mL) was boiled for 1 h, cooled to 100°C, stirred, treated with TiCl (2.5 g, 13.16 mmol) in (CH CO) O (2.5 mL), boiled
4
3
2
an additional 2 h, cooled to 40°C, treated gradually with CH COONa (10 g) dissolved in water (25 mL), stirred 20 min, cooled
3
to room temperature, poured intoCH COCH (220 mL) and CH COOH (220 mL), oxidized byaddition of CrO (15 g) in water
3
3
3
3
(7.5 mL) at 15-18°C, stirred an additional hour, treated with isopropanol (7.5 mL), gradually heated to distill off acetone and
reach a temperature of115-117°C, boiled for 1.5 h, cooled to room temperature, and treated with water (425 mL). The resulting
precipitate was filtered off, washed with water, and recrystallized from methanol:acetone (3:1) to afford 2 (29 g, 69.5%),
mp 158-162°C, lit. mp 158-162°C [11].
5α-Pregn-16-en-3β-ol-20-one Acetate Oxime (3). A mixture of 2 (2.5 g, 6.97 mmol), NH OH·HCl (0.55 g,
2
7.91 mmol), and dry C H N (12 mL) was heated at 65-68°C for 2 h, cooled to room temperature, treated with water (45 mL),
5
5
and stirred for 30 min. The resulting precipitate was filtered off and washed with water to afford 3 (2.5 g, 98.07%), mp 196-
198°C, lit. mp 195.5-198.5°C [13].
3β-Acetoxy-5α-androstan-17-one (5). A mixture of 3 (1 g, 2.67 mmol), dry C H N (3.2 mL), and dry CH COCH
3
5
5
3
(3.2 mL) at 18-20°C was treated with POCl (1.2 mL), stirred for 30 min, cooled to -5°C, treated with dilute HCl (1:1 with
3
water, 28 mL), stirred for 30 min, and treated with water until neutral. The resulting precipitate was filtered off and washed
with water to afford crude product (0.83 g) that was chromatographed over a column of silica gel (L 100-160) with elution by
low-boiling petroleum ether:ether (20:1) to afford 5 (0.58 g, 65%), mp 111-113°C, lit. mp 111-113°C [13].
3β-Acetoxy-5α-androstan-17β-ol (6). A solution of 5 (4.7 g, 14.13 mmol) in methanol (10 mL) at 0°C was treated
in portions with NaBH (1 g, 26.31 mmol), stirred at 20°C for an hour, acidified with acetic acid until weaklyacidic, and poured
4
into water (200 mL). The precipitate was filtered off, washed with water, and recrystallized from methanol to afford 6,
-1
(0.97 g, 97%), mp 106-107°C, lit. mp 106.5°C [14]. IR spectrum ( , cm ): 3455 (OH).
5α-Androstan-3β,17β-diol (7). A solution of 6 (4.46 g, 13.33 mmol) in methanol (100 mL) was treated with NaOH
(0.53 g), boiled for 10 min, cooled, evaporated to 40 mL, and poured into water. The resulting precipitate was filtered off,
washed with water until the rinsings were neutral, and recrystallized from benzene:hexane (10:1) to afford 7, (4.2 g, 95%),
-1
mp 163-165°C, lit. mp 161°C [15]. IR spectrum (ν, cm ): 3504 (OH). PMR spectrum (ppm): 0.61 (3H, s, CH -18), 0.72 (3H,
3
13
s, CH -19), 3.18 (1H, br.s, OH-C-3), 3.4 (1H, br.s, OH-C-17), 4.3 (1H, s, C-3), 4.3 (1H, s, C-17), C NMR spectrum (δ, ppm):
11.37 (C-18), 12.22 (C-19), 60.39 (C-3), 80.13 (C-17). Mass spectrum (m/z, I , %): 292 (7) [M] , 257 (12), 208 (15).
3
+
rel
REFERENCES
1.
2.
3.
4.
I. Kozak, W. Bartsch, M. Krieg, and K. D. Voigt, Prostate, 3, 433 (1982).
L. Pylkkanen, S. Makela, and R. Santti, Eur. J. Urol., 30, 243 (1996).
A. Jemal, A. Thomas, T. Murray, and M. Thun, CA Can. J. Clin., 52, 23 (2002).
W. Zhang, S. Makela, L. C. Andersson, S. Salmi, S. Saji, J. I. Webster, E. V. Jensen, S. Nilsson, M. Warner, and
J.-A. Gustafsson, Proc. Natl. Acad. Sci. USA, 98, 6330 (2001).
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