Au. Siddiqui et al., INHIBITORS OF STEROL SYNTHESIS - SYNTHESIS AND SPECTRAL PROPERTIES OF6,26,27,27,27-HEPTAFLUORO-5-ALPHA-CHOLESTAN-15-ONE, Chemistry and physics of lipids, 86(2), 1997, pp. 95-119
3 beta-Hydroxy-25,26,26,26,27,27,27-heptafluoro-5 alpha- cholestan-15-
one (4) has been prepared as part of a program to synthesize 15-ketost
erols that are not readily metabolized to cholesterol or side-chain ox
ygenated species. Saponification of 3 beta-acetoxy-5 alpha-chola-8(14)
,23-dien-15-one (5) followed by lithium-ammonia reduction with a bromo
benzene quench gave 3 beta-hydroxy-5 alpha-chol-23-en-15-one (6). Addi
tion of (CF3)(2)CFI to 6 in the presence of triethylborane gave an iod
ide preparation, which was reduced to 4 with tributyltin hydride (71%
overall yield of 4 from 5). The 23-iodide preparations consisted of 6:
1 mixtures of (23R)-3 -hydroxy-23-iodo-25,26,26,26,27,27,27-heptafluor
o- 5 alpha-cholestan-15-one (9a) and its 15-one (9a) and its C-23 epim
er 9b with variable amounts of 4. Compound 4 was also prepared by lith
ium-ammonia reduction of the Delta(8(14)) analogs of 4 and iodides 9a
and 9b. The presence of small amounts of 6 in the latter product sugge
sted a side reaction involving cleavage of the C24-C25 bond with loss
of a (CF3)(2)CF . radical. Also prepared were 25,26,26,26,27,27,27-hep
tafluoro-5 alpha-cholestane-3 beta, 15 alpha-diol, its 15 beta epimer,
the 7 alpha-methyl analog of 4, 3 beta-hydroxy-7 alpha-methyl-5 alpha
-cholestan-15-one (16), and (25R)-3 beta,26-dihydroxy-5 alpha-cholesta
n-15-one. Full H-1 and C-13-NMR data of high precision with complete s
ignal assignments are given for all new compounds. Definitive H-1-NMR
stereochemical assignments of the C-24 protons were established for mo
st sterols with a C8H17 side chain based on analysis of the downfield
H-24 resonance in a 750-MHz spectrum of 16. Detailed electron-impact m
ass spectral data are presented together with a summary of major fragm
entation patterns for 15-hydroxy- and 15-ketosteroids with and without
a Delta(8(14)) bond. (C) 1997 Elsevier Science Ireland Ltd.