The Chemistry of Vicinal Tricarbonyls: Total Syntheses of Elastase Inhibitors YM-47141 and YM-47142

Abstract

We have completed the total syntheses of elastase inhibitors YM-47141 and YM-47142, the first natural products containing a vicinal tricarbonyl group. The work establishes the configuration at C(4) of the macrocyclic depsipeptide and demonstrates the generality of the phosphoranylidene-ylide activation and protection methodology employed earlier in syntheses of α-keto amides. Key steps involve the coupling of a carboxylic acid with a phosphorane to form a stable ylide intermediate, which contains the highly electrophilic carbonyl group in protected form. The tricarbonyl unit was unmasked at the final stage of the synthesis by oxidative cleavage of the C=P bond.