Aldol reactions of ketal-protected tartrate ester enolates. Asymmetric syntheses and absolute stereochemical assignments of phospholipase A2 inhibitors cinatrin C1 and C3

Abstract An efficient approach to the syntheses of cinatrins C 1 and C 3 has been developed and used to establish the absolute configurations of these natural products. The construction of each molecule has been achieved in a five-step reaction sequence (overall yield 43% for cinatrin C 1 , 33% for cinatrin C 3 ) from the di- tert -butyl ester of ( R , R )-tartaric acid. The two contiguous, quaternary chiral centers in the cinatrin skeleton are constructed via a diastereoselective, titanium-mediated aldol coupling of a tartrate-derived silylketene acetal and an achiral α-ketoester. This bond construction proceeds with excellent diastereoselectivity for a variety of aldehyde and α-ketoester substrates.