Synthesis of C21-C41 fragment of the reported structure of Neaumycin B

Abstract

Stereoselective synthesis of the C₂₁-C₄₁ fragment 4 of the reported structure of Neaumycin B(1), a 28-membered macrolide compound with 19-chiral centers and 6,6-spiroketal structure, has been described. C₂₁-C₂₇ fragment 5 was synthesized from the commercially available (S)-Roche ester 7 using stereoselective allylation and Brown anti-crotylation as key steps. C₂₈-C₄₁ fragment 6 was constructed from chiral oxazolidinone auxiliary 13 using Evans syn-aldol reaction, diastereoselective epoxidation, and (S)-CBS reduction as key steps. Finally, boron-mediated acetate aldol reaction of 5 and 6 led to the synthesis of C₂₁-C₄₁ fragment 4 for the reported structure of Neaumycin B (1).