STEREOCONTROLLED SYNTHESIS OF C10-C22 FRAGMENT OF THE IMMUNOSUPPRESSANT FK-506 - AN OCCURRENCE OF COMPLEMENTARY STEREOSELECTIVITY IN THE C15 KETONE REDUCTION

The stereoselective syntheses of the C10-C22 fragment 2a and its C15-e pimer 2b of the immunosuppressant FK 506 1 have been carried out throu gh convergent coupling of the sulfone 3, which could be constructed by highly stereocontrolled ester-enolate Claisen rearrangement of ene-es ter 5, and the aldehyde 4 which was prepared from D-mannitol via anti selective methallylsilane addition to aldehyde 6 followed by modest st ereoselective hydroboration based on 1,3-asymmetric induction. In the course of this reaction sequence a complementary stereoselection depen dent on the used hydride reagents has occurred in reduction of the cou pling product 26. Copyright (C) 1996 Elsevier Science Ltd