Total Synthesis of the Proposed Structure of Neaumycin B

Abstract

The total synthesis of the proposed structure of anti-glioblastoma natural product neaumycin B was achieved in 22 steps (longest linear sequence). The synthesis features HCl-mediated [6,6]-spiroketalization, a combination of Krische iridium-catalyzed crotylation, Marshall palladium-catalyzed propargylation, Fürstner nickel-catalyzed regio- and enantioselective vicinal monoprotected diol formation, Brown crotylation and asymmetric halide-aldehyde cycloaddition, so as to establish the challenging contiguous stereocenters.

Keywords: Antitumor Agents; C−C Coupling; Macrolide Natural Products; Spiroketalization; Total Synthesis.