Solid phase synthesis of depsides and depsipeptides

Abstract

A general solid phase methodology for the synthesis of depside and depsipeptide chains from optically active α-hydroxy acids and α-amino acids is reported. The automated preparation of depsides (97% yield per cycle) made up from the same enantiomer [i.e. H-[( S)-Man] 8-OH, 1] † † Abbreviations for α-hyroxy acids and depsides are consistent with those used for α-amino acids and peptides in the nomenclature of peptides, with “H” representing the hydroxy group and “OH” representing the carboxy group: H-Hiv-OH = α-hydroxyisovaleric acid; H-Lac-OH = lactic acid; H-Man-OH = mandelic acid. by both enantiomers [i.e. H-[( R)-Man-( S)-Man] 4-OH, 2], or by different hydroxy acids in the same chain [i.e. H-[( S)-Lac-( S)-Hiv] 3-OH, 3], and of depsipeptides where α-amino and α-hydroxy acids are alternatively introduced such as depsipeptide 6 (Cbz-[( S)-Val-( R)-Man-( R)-Val-( S)-Lac] 3-OH), are presented. Cyclization of the open chain depsides leads to chiral macrocycles whose structures resemble those of crown ethers.