Stereocontrolled synthesis of C10-C22 fragment of the immunosuppressant FK 506. An occurrence of complementary stereoselectivity in the C15 ketone reduction

Abstract

The stereoselective syntheses of the C10-C22 fragment 2a and its C15-epimer 2b of the immunosuppressant FK 506 1 have been carried out through convergent coupling of the sulfone 3, which could be constructed by highly stereocontrolled ester-enolate Claisen rearrangement of ene-ester 5, and the aldehyde 4 which was prepared from D-mannitol via anti selective methallylsilane addition to aldehyde 6 followed by modest stereoselective hydroboration based on 1,3-asymmetric induction. In the course of this reaction sequence a complementary stereoselection dependent on the used hydride reagents has occurred in reduction of the coupling product 26.