18-substituted-19-nor-vitamin D compounds

A method of making a ketone of the formula

• where R is represented by the structure:
• where the stereochemical center at carbon 20 may have the R or S configuration, and where Z is selected from Y, —OY, —CH2OY, —C≡CY and —CH═CHY, where the double bond may have the cis or trans geometry, and where Y is selected from hydrogen, methyl, —COR5 and a radical of the structure:
• where m and n, independently, represent the integers from 0 to 5, where R1 is selected from hydrogen, deuterium, hydroxy, protected hydroxy, fluoro, trifluoromethyl, and C1-5 -alkyl, which may be straight chain or branched and, optionally, bear a hydroxy or protected-hydroxy substituent, and where each of R2, R3 and R4, independently is selected from deuterium, deuteroalkyl, hydrogen, fluoro, trifluoromethyl and C1-5 alkyl, which may be straight-chain or branched, and optionally, bear a hydroxy or protected-hydroxy substituent, and where R1 and R2, taken together, represent an oxo group, or an alkylidene group, ═CR2R3, or the group —(CH2)p—, where p is an integer from 2 to 5, and where R3 and R4, taken together, represent an oxo group, or the group —(CH2)q—, where q is an integer from 2 to 5, and wherein any of the CH-groups at positions 20, 22, or 23 in the side chain may be replaced by a nitrogen atom, or where any of the groups —CH(CH3)—, —CH(R3)—, —CH(R2)— at positions 20, 22 and 23, respectively, may be replaced by an oxygen or sulfur atom, and further wherein R5 is a protected-hydroxy group, which comprises the steps of selectively tosylating a diol of the formula
• to obtain a mono-tosolyate of the formula
• thereafter converting the mono-tosylate to an acetylenic compound having the formula
• catalytically hydrogenating the acetylenic bond to obtain a hydroxylated derivative of the formula
• and oxidizing the hydroxylated derivative to said ketone.