An approach to the total synthesis of lankacidins: synthesis of advanced macrocyclic precursors

The macrocyclic tetraenes 11 and 19, possible precursors of lankacidin C 1, have been prepared using intramolecular Stille reactions to close the macr ocyclic rings. The Stille precursor 10 was prepared by stereoselective acyl ation of the azetidinone 3 using the thioester 7. After reduction and depro tection, cyclisation gave the macrocyclic product 11 in 55% yield. Alternat ively, the Boc-protected amino-ester 17 was prepared by ring-opening of the azetidinone, and cyclised to the macrocycle 19 in 48% yield. (C) 2001 Else vier Science Ltd. All rights reserved.