156273-88-0Relevant articles and documents
Inhibitors of sterol synthesis. Synthesis and spectral properties of 3β-hydroxy-25,26,26,26,27,27,27-heptafluoro- 5α-cholestan-15-one
Siddiqui, Abdul U.,Swaminathan, Shankar,Su, Xiangdong,Wilson, William K.,Schroepfer Jr., George J.
, p. 95 - 119 (1997)
3β-Hydroxy-25,26,26,26,27,27,27-heptafluor 5α-cholestan-15-one (4) has been prepared as part of a program to synthesize 15-ketosterols that are not readily metabolized to cholesterol or side-chain oxygenated species. Saponification of 3β -acetoxy-5α-chola-8(14),23-dien-15-one (5) followed by lithium-ammonia reduction with a bromobenzene quench gave 3β-hydroxy-5α-chol-23-en-15-one (6). Addition of (CF3)2CFI to 6 in the presence of triethylborane gave an iodide 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)-3β -hydroxy-23-iodo-25,26,26,26,27,27,27-heptafluoro 15-one (9a) and its C-23 epimer 9b with variable amounts of 4. Compound 4 was also prepared by lithium-ammonia reduction of the Δ814 analogs of 4 and iodides 9a and 9b. The presence of small amounts of 6 in the latter product suggested 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-heptafluoro-5α-cholestane-3β,15α-diol, its 15β epimer, the 7α-methyl analog of 4, 3β-hydroxy-7α-methyl-5α-cholestan-15-one (16), and (25R)-3β,26-dihydroxy-5α-cholestan-15-one. Full 1H and 13C-NMR data of high precision with complete signal assignments are given for all new compounds. Definitive 1H-NMR stereochemical assignments of the C-24 protons were established for most 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 mass spectral data are presented together with a summary of major fragmentation patterns for 15-hydroxy-and 15-ketosteroids with and without a Δ814 bond.
