The chemistry of vicinal tricarbonyls: Total syntheses of elastase inhibitors YM-47141 and YM-47142

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