SYNTHESIS OF ALKENE DIPEPTIDE ISOSTERES EMPLOYING THE WITTIG-STILL REARRANGEMENT

A new approach to the synthesis of alkene dipeptide isosteres is reported which features the use of the [2,3]-Wittig-Still rearrangement, carried out in hexanes. Employing this rearrangement alkene dipeptide isosteres of ''Gly-Xxx'' are accessible starting from an alpha-beta-unsaturated carbonyl compound. This is illustrated with the synthesis of the alkene dipeptide isostere of Gly-Ala as part of the tripeptide isostere Cbz-Phe-Gly-psi[E-CH=CH]-(R,S)Ala-OH 20, starting from crotonaldehyde. Alkene dipeptide isosteres of''Xxx-Gly'' arc accessible starting from an a-amino aldehyde derivative. As an example the synthesis of the dipeptide isostere of Phe-Gly as part of the tripeptide isostere Cbz-Phe-Phe-psi[E-CH=CH]-Gly-OH 28 is described for which N-Tr-phenylalaninal was used as a starting material.