Microwave irradiation dramatically improves the efficiency of ring closing metathesis (RCM) reactions of resin-attached peptides and the technology is illustrated by the highly selective synthesis of dicarba analogues of alpha-conotoxin IMI.

No abstract

Installation of reversible, metathesis-active tethers into linear peptide sequences can be used to promote formation of cyclic peptide amides and esters.

A method to facilitate regioselective formation of multiple dicarba isosteres of cystine is described. A sequence of ruthenium-catalyzed cross metathesis and rhodium-catalyzed hydrogenation of nonproteinaceous allylglycine derivatives has been developed to achieve high-yielding and unambiguous formation of diaminosuberic acid derivatives. Allylglycine derivatives readily undergo ruthenium-catalyzed metathesis and hydrogenation to yield diaminosuberic acid derivatives in near quantitative yield. Under the same experimental conditions, prenylglycine was found to be inert to both Grubbs' and Wilkinson's catalyzed metathesis and hydrogenation, respectively, but was readily activated for metathesis via cross metathesis with Z-butene. Subsequent cross metathesis of the metathesis-formed crotylglycine derivative, followed by hydrogenation, yielded the second diaminosuberic acid derivative in excellent yield.

The cross-metathesis of synthetic and natural triglycerides containing unsaturated fatty acids with 2-butene can be achieved with high conversion and excellent productive turnovers. These reactions are catalysed by second-generation ruthenium-based olefin metathesis catalysts and can be conducted at -5 degrees C in liquid 2-butene.

Bis-dicarba analogues of native dicystine-containing alpha-conotoxin Rg1A, an analgesic peptide isolated from cone snail venom, were constructed on resin using a regioselective metathesis-hydrogenation strategy.

No abstract

A combination of homogeneous hydrogenation and metathesis reactions allows highly efficient, stepwise chemo- and stereoselective formation of three separate 2,7-diaminosuberic acid derivatives in a single pot without isolation of intermediates.