Epimeric 3a a,7a a,16-and 3a a,7a a,15-trihydroxy-5b b-cholan-24-oic acids and some related compounds were synthesized from chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), respectively. The key reaction involved one-step remote oxyfunctionalization of unactivated methine carbons at C-17 of CDCA and at C-14 of UDCA as their methyl ester-peracetate derivatives with dimethyldioxirane (DMDO). After dehydration of the resulting 17a a-and 14a a-hydroxy derivatives with POCl 3 or conc. H 2 SO 4 , the respective D D 16 -and D D 14 -unsaturated products were subjected to hydration via hydroboration followed by oxidation to yield the 3,7,16-and 3,7,15-triketones, respectively. Stereoselective reduction of the respective triketones with tert-butylamine-borane complex afforded the epimeric 3a a,7a a,16-or 3a a,7a a,15-trihydroxy derivatives exclusively. A facile formation of the corresponding e e-lactones between the side chain carboxyl group at C-24 and the 16a a-(or 16b b-) hydroxyl group in bile acids is also clarified.

Remote oxy-functionalization of methyl 3α-acetoxy-and 3-oxo-5β-cholan-24-oates with 2,6-dichloropyridine (DCP) N-oxide catalyzed by (5,10,15,20-tetramesitylporphyrinate) ruthenium (II) carbonyl complex [Ru(TMP)CO] and HBr was compared with that with dimethyldioxirane (DMDO). Treatment of the 5β-steroids with DMDO afforded the corresponding 5β-and 17α-monohydroxylated and 5β,14α-and 5β,17α-dihydroxylated compounds. On the other hand, the corresponding 20S-mono-and 5β,20S-dioxygenated derivatives (as the γ-lactones), along with 5β-hydroxy compounds, were found to be the major oxidation products of the 5β-steroids with the DCP N-oxide / Ru(TMP)CO / HBr system. Both the reagents oxidized unactivated methine carbons stereoselectively, but the degree of regioselectivity depended upon the oxidants employed and the structure of the hydroxyl-protecting groups at C-3 (acetoxyl or carbonyl) of the substrates.

Direct remote functionalization of unactivated carbons by dimethyldioxirane (DMDO) was examined for 3alpha,6- and 3alpha,24-dihydroxy-5beta-cholane derivatives. DMDO oxidation of stereoisomeric methyl 3alpha,6-diacetoxy-5beta-cholanoates caused the direct, unexpected 14alpha- and 17alpha-hydroxylations, in analogy with that of the 5alpha-H analogs, regardless of the differences in stereochemical configuration of the A/B-ring junction and of the acetoxyl groups at C-3 and C-6. On the other hand, the ester derivatives of 3alpha,24-dihydroxy-5beta-cholane with DMDO were transformed into the corresponding 5beta-, 14alpha-, and 17alpha-hydroxy compounds, whereas the ether derivatives yielded the 5beta-hydroxy, 3-oxo, and C-24 oxidized products, accompanied by their dehydrated ones.

An improved method for a suitable derivatization of polyhydroxylated steroids having one or two tert-hydroxyl groups at the 5beta-, 14alpha-, 17alpha-, 24-, and/or 25-positions by capillary gas chromatography (CGC) is described. By using trimethylsilyl triflate as a silylating reagent and 2,6-lutidine as a catalyst, each of 5beta-cholane and 5alpha-cholestane series of steroids was successfully transformed into trimethylsilyl (TMS) ether derivatives to give a single CGC peak under mild conditions. More bulky triethylsilyl (TES) etherification of 14alpha- and 17alpha-hydroxy compounds provided multiple CGC peaks arising from completely- and/or incompletely-derivatized TES ethers accompanied by their thermal elimination products.