INHIBITORS OF STEROL SYNTHESIS - SYNTHESIS AND SPECTRAL PROPERTIES OF6,26,27,27,27-HEPTAFLUORO-5-ALPHA-CHOLESTAN-15-ONE

Citation
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
Citations number
53
Categorie Soggetti
Biology
ISSN journal
00093084
Volume
86
Issue
2
Year of publication
1997
Pages
95 - 119
Database
ISI
SICI code
0009-3084(1997)86:2<95:IOSS-S>2.0.ZU;2-6
Abstract
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.