IMPROVED SYNTHETIC ROUTE TO DEXAMETHASONE ACETATE FROM TIGOGENIN

In the synthesis of dexamethasone acetate from tigogenin, the introduc tion of the 17 alpha-hydroxy-16 alpha-methyl and the 1,4-diene moietie s was improved. For the introduction of the 17 alpha-hydroxy-16 alpha- methyl moiety, the key step, epoxidation, was accomplished in high yie ld with peracetic acid in a buffer solution of sodium acetate and acet ic acid (overall yield from 17-ene substrate to 17 alpha-hydroxy-16 al pha-methyl intermediate: 95.3%). Then the introduction of the 1,4-dien e in the A-ring was greatly improved by bromination-dehydrobromination , in which dehydrobromination proceeded smoothly in a solvent system t hat was a mixture of DMF and 6% of water (82.6% isolated yield of 1,4- diene based on 3-oxo compound).