Smilagenin Transformation Products Under Lewis Acid Catalysis in Acetic Anhydride and Synthesis of 23-Acetyl-Spirostanols.

Objective: The present contribution describes a novel approach for obtaining steroid derivatives of the iso-type from sapogenins for drug discovery. Methodology: Diastereomeric 23-acetyl-spirostanols were prepared by acetolysis of smilagenin (4) (25R) using boron trifluoride diethyl etherate in acetic anhydride followed by treatment of the epimeric epoxycholestene obtained (6 or 9) under basic hydrolysis. Higher regioselectivity was attained in the presence of ZnCl₂ in acetic anhydride. Results: Acetolysis of smilagenin (4) (25R) using boron trifluoride diethyl etherate in acetic anhydride afforded 20-α-methyl epoxycholestene 6 as the major product, two furostene derivatives (7 and 8), as well as the new 20-β-methyl epoxycholestene 9. Increased regioselectivity for the acetolysis of smilagenin (4) was observed using ZnCl₂ in acetic anhydride affording 6 in 90% yield. Subsequent treatment of the epimeric epoxycholestene (6 or 9) under basic hydrolysis afforded two new diastereomeric 23-acetyl-spirostanols 14 and 15. The structures of all compounds were established using 1D and 2D NMR techniques. Conclusions: Formation of the two diastereomeric 23-acetyl-spirostanols (14 and 15) from epimeric epoxycholestenes 6 and 9 with KOH/EtOH proceeds with high stereospecificity. The configuration at C-20, C-22, C-23, and C-25 for the new iso-type 23-acetyl-spirostanol 15 was established by X-ray crystal analysis as 20R, 22R, 23S, and 25R. In addition to the above, the X-ray of 15 was analyzed and compared with the crystallographic data of sarsasapogenin acetate (16), smilagenin (4) and 23-acetyl-sarsasapogenin (17). [ABSTRACT FROM AUTHOR]