Synthesis and stereochemistry of ficisterol and norficisterol: biosynthetic implications

Abstract
All four possible C-23 and C-24 stereoisomers of ficisterol and norficisterol were synthesized via Ireland's ester enolate Claisen rearrangement. The stereochemistry of each isomer was determined by a combination of stereochemical deductions derived from the Claisen mechanism, and chemical correlations with known standards. The resulting stereostructures (1a) and (2a) are consistent with the hypothesis that dihydrocalysterol (3) and (23R,24R)-methylenecholesterol (42) are the respective biosynthetic precursors of ficisterol and norficisterol, thus supporting a novel mechanism for 27-norergostane biosynthesis. In the course of the stereochemically significant synthesis, 23,24-dimethyl-22-dehydrocholesterol (37)—the presumed biosynthetic precursor of gorgosterol (41)—was prepared by a route that lends itself readily to the synthesis of isotopically labelled analogues.

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