Pactamycin and Its Derivatives: Improved Synthesis Route

Abstract

Stereoselective construction of the cyclopentane core 21 of pactamycin (1) was achieved from symmetric cyclohexadiene 7. Our synthetic strategy features catalytic Rh‐mediated desymmetric aziridination of the cyclohexadiene derivative, selective ring‐opening reaction at the C2 position of sulfonylaziridine with NaN3, ring‐contraction of cyclohexene 9 by ozonolysis followed by intramolecular aldol reaction via enamine intermediate 11, and construction of the two consecutive tetra‐substituted carbon centers by stereoselective epoxidation of the exo‐methylene moiety of 14c with DMDO, followed by methylation reaction. Introduction of the urea unit on tetra‐substituted carbon of 16 was achieved by amidation and subsequent Hofmann rearrangement.