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

An efficient approach to the syntheses of cinatrins C₁ and C₃ 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 C₁, 33% for cinatrin C₃) 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.