TOTAL SYNTHESIS OF THE MACROLIDE ANTITUMOR ANTIBIOTIC LANKACIDIN-C

The first total synthesis of natural (-)-lankacidin C (I) has been ach ieved by a convergent, enantioselective sequence starting from D-arabi nose and L-aspartic acid, proceeding through the tricyclic carbamate 1 5 as an advanced relay intermediate. Specifically, the beta-lactam die ne intermediate 41 is acylated by the thiopyridyl ester 34c. The resul ting beta-ketolactam 42 is stereospecifically reduced by KEt(3)BH to c arbinol 43, which on desilylation undergoes acid-catalyzed N --> O acy l migration to yield the delta-lactone 44. The derived iodo aldehyde 4 6 undergoes Stille coupling to give tetraene 54a, which upon Stork-Tak ahashi cyclization to ketone 56 and CBS reduction gives the key relay 15. N-acylation of the latter, and then regioselective carbamate sciss ion followed by Dess-Martin oxidation, produces the target antibiotic (-)-lankacidin C (1).