THE TOTAL SYNTHESIS OF (+)-IONOMYCIN

The total synthesis of (+)-ionomycin, a dibasic acid ionophore, is described by using a strategy that capitalizes on the chiron approach and on asymmetric processes. The C1-C22 portion of ionomycin was constructed from smaller segments obtained in optically pure form by systematic functionalization and manipulation of chirons derived originally from L-glutamic acid. A key reaction in the synthesis of the deoxypropionate-containing segments relies on a novel sulfur-assisted organocuprate displacement of a secondary tosylate with complete inversion of configuration. The tetrahydrofuran segment of ionomycin was constructed from an optically pure epoxide obtained via a Sharpless asymmetric epoxidation and a sulfone derived from geraniol. © 1990, American Chemical Society. All rights reserved.