STEREOSELECTIVE SYNTHESIS OF A 2,2,5-TRISUBSTITUTED TETRAHYDROPYRAN CHIRON VIA 1,3-ASYMMETRIC AND 1,6-ASYMMETRIC INDUCTION - A TOTAL SYNTHESIS OF (-)-MALYNGOLIDE

A new mode of synthesizing chiral 2,2,5-trisubstituted tetrahydropyran is described, in which two chiral centers are simultaneously introduc ed via facial and group selective nucleophilic acetal cleavage reactio n of a bicyclic acetal 1, thereby accomplishing 1,3- and 16-asymmetric induct ion. It is revealed that acetal cleavage of the pro-R C-O bond and nucleophilic attack opposite the cleaved bond proceed preferentia lly. With TiCl4 and at lyltrimetyl silane at -100 degrees C, the selec tivity of acetal fission is 10:1 and that of nucleophilic at tack is 1 2:1. This reaction is successfully applied to a total synthesis of mar ine antibiotics, (-)-malyngolide. (C) 1998 Elsevier Science Ltd. All r ights reserved.