Structural and biosynthetic studies of a principal bile alcohol, 27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25-pentol, in human urine

The stereochemistry at C-24 and C-25 of 27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25-pentol, a principal bile alcohol in human urine, and i ts biosynthesis are studied. Four stereoisomers of the C-26-24,25-pentols w ere synthesized by reduction with LiAlH4 of the corresponding epoxides prep ared from (24S)- or (24R)-27-nor-5 beta-cholest-25-ene-3 alpha, 7 alpha,12 alpha,24-tetrol. The stereochemistries at C-25 were deduced by comparison o f the C-26-24,25-pentols with the oxidation products of (24Z)-27-nor-5 beta -cholest-24-ene-3 alpha,7 alpha,12 alpha-triol with osmium tetraoxide. On t he basis of this assignment, the principal bile alcohol excreted into human and rat urine was determined to be (24S, 25R)-27-nor-5 beta-cholestane-3 a lpha,7 alpha,12 alpha,24,25-pentol, accompanied by a lesser amount of (24R, 25R)-isomer. To elucidate the biosynthesis of the C-26-24,25-pentol, a puta tive intermediate, 3 alpha,7 alpha,12 alpha-trihydroxy-27-nor-5 beta-choles tan-24-one, derived from 3 alpha,7 alpha,12 alpha-trihydroxy-24-oxo-5 beta- cholestanoic acid by decarboxylation during the side-chain oxidation of 3 a lpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid, was incubated wi th rat liver homogenates. The 24-oxo-bile alcohol could be efficiently redu ced to yield mainly (24R)-27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha ,24-tetrol. If a 25R-hydroxylation of the latter steroid occurs, it should lead to formation of (24S,25R)-C-26-24,25-pentol. Now it has appeared that a major bile alcohol excreted into human urine is (24S,25R)-27-nor-5 beta-c holestane-3 alpha,7 alpha,12 alpha,24,25-pentol, which might be derived fro m 3 alpha,7 alpha,12 alpha-trihydroxy-27-nor-5 beta-cholestan-24 one via (2 4R)-27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24-tetrol.