Bioinspired Synthesis of Platensimycin from Natural ent-Kaurenoic Acids

Abstract

The biomimetic formal synthesis of the antibiotic platensimycin for the treatment of infection by multidrug-resistant bacteria was accomplished starting from either ent-kaurenoic acid or grandiflorenic acid, each of which is a natural compound available in multigram scale from its natural source. Apart from the natural origin of the selected precursors, the keys of the described approach are the long-distance functionalization of ent-kaurenoic acid at C11 and the efficient protocol for the A-ring degradation of the diterpene framework.

Asymmetric Synthesis and Biological Evaluation of Platensilin, Platensimycin, Platencin, and Their Analogs via a Bioinspired Skeletal Reconstruction Approach

“…PTM ( 2 ) and PTN ( 3 ) have garnered substantial interest from biological, biogenetic, and synthetic − perspectives. Over the past 20 years, a number of elegant and efficient chemical syntheses of PTM ( 2 ) and PTN ( 3 ) have emerged since the landmark synthesis of (±)-PTM ( 2 ) by Nicolaou et al in 2006 .…”

“…Over the past 20 years, a number of elegant and efficient chemical syntheses of PTM ( 2 ) and PTN ( 3 ) have emerged since the landmark synthesis of (±)-PTM ( 2 ) by Nicolaou et al in 2006 . Sequential bond-forming cyclization strategies have been extensively investigated to construct the bicyclo[3.2.1]-octane and bicyclo[2.2.2]-octane cores of PTM ( 2 ) and PTN ( 3 ), respectively (see Figure S1A in Supporting Information). Despite significant advances in this field, the unified approach toward these biogenetically related natural products is still limited, with only two divergent approaches reported by Nakada and Lee for the synthesis of PTM ( 2 ) and PTN ( 3 ), respectively (Figure C) .…”