Four major byproducts qf the Clcmmensen reduction of diosgwdn have ken isolated and kienti_Red: (2SR)-l7fi mcthyl-18-~r-17~cholesta-5.13-~~-3~~6-~1. dihydrodiosgenin, (22E~SR)-choiesta-522-dicncJs.16B26-ui, and its 222 isomer. These bproducts were used to prepare deuteriwn-and tritium4abeled (2SR)-26+droqvcholesterol(3) and J2 analogs o/3.
Mitochondrial 26-hydroxylation of sterols is an obligatory reaction in major pathways of bile acid formation3 and is an initial reaction in the metabolism of 3I.+hydroxy-Sa-cholest-8( )-en-15-one, a potent hypocholesterolemic agent.4 The products of 26-hydroxylation, i.e. (25R)-26-hydroxycholesterol (3)s and (25R)-26-oxygenated-l5-ketosterols.6 are highly active in the regulation of sterol synthesis in cultured mammalian cells. The initial step in the chemical synthesis of (25R)-C-26 functionalixed sterols is generally the Clemmensen reduction of a sapogenin,h7 a reaction that often proceeds in modest or variable yield. In the case of diosgenin (l), this reaction affords an almost quantitative recovery of steroid material, of which the desired 3g,16p,26-triol4 and recovered diosgenin constitute at most -75%. Clemmensen reduction byproducts of sapogenins have been investigated only for the case of tigogenin (2). which was reported to give a 63:37 ratio of (25R)-Sa-cholestane-3B,16@6-trio1 and the 22s isomer of dihydrotigogenin.* The latter was said to decompose readily to A22-and A23-3g,16g,26-triols, from which it could not be separated. Additionally, the main trio1 product was shown to be transformed to (25R)-17~-methy1-l8-nor-5a,17a-cholest-l3-ene-3~,26-diol under acidic conditions. In the Clemmensen reduction of diosgenin, we have observed the corresponding 1%norstem but have found different structures and reactivities for the other byproducts. We describe hem the isolation and identification of four major byproducts in the Clemmensen reduction of diosgenin. Deuterium-and nitiumlabeled 3 and analogs of 3 with Am unsaturation were prepared from these byproducts.