Biomimetic synthesis and structural refinement of the macrocyclic dimer aminoglycoside 66-40C—the remarkably selective self-condensation of a putative aldehyde intermediate in the submerged culture medium producing sisomicin

Abstract

Aminoglycoside 66-40C, an unprecedented 16-membered bis-azadiene macrocyclic natural product isolated from the Micromonospora producer of the antibiotic sisomicin, was synthesized following a biomimetic strategy which definitively established its origin as arising from a remarkably selective non-enzymatic macro-dimerization.