ANTINEOPLASTIC AGENTS .320. SYNTHESIS OF A PRACTICAL PANCRATISTATIN PRODRUG

Owing to its sparingly soluble properties, the potential anticancer dr ug pancratistatin (1) resisted conventional drug formulation procedure s and the synthesis of a water-soluble prodrug became necessary. That important objective for further pre-clinical development was met by de vising a route to a disodium phosphate derivative (5). The key step in the synthesis of the phenolic phosphate was phosphorylation of 1,2,3, 4-tetraacetoxy-pancratistatin (2) with dibenzyloxy(N,N-diisopropylamid o)phosphine. Subsequent oxidation with m-chloroperbenzoic acid afforde d phosphate 4a. Hydrogenolysis of the benzyl esters followed by base-c atalysed hydrolysis of the acetate groups led to the water-soluble pro drug 5 in high yield.