Step-wise and pre-organization induced synthesis of a crossed alkene-bridged nisin Z DE-ring mimic by ring-closing metathesis??

Organic & Biomolecular Chemistry Pub Date: 2007-02-07 DOI: 10.1039/B618085J

Abstract

This paper describes two approaches for the synthesis of a crossed alkene-bridged mimic of the thioether ring system of the nisin Z DE-fragment. The first approach comprised the stepwise total synthesis featuring a cross metathesis and a macrolactamization on a solid support followed by a ring-closing metathesis in solution. Via this route the title compound was obtained in an overall yield of 7% (85% on average for 16 reaction steps). In the second approach, the linear precursor peptide was subjected to ring-closing metathesis and the bicyclic peptide with the correct side chain connectivity pattern was obtained in yields up to 95%. The preferred formation of the bicyclic crossed alkene-bridged mimic of the DE-ring suggests a favorable pre-organization of the linear precursor peptide.

Graphical abstract: Step-wise and pre-organization induced synthesis of a crossed alkene-bridged nisin Z DE-ring mimic by ring-closing metathesis
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