Syntheses of Acyclic Analogs of Didemnin B

Abstract

The syntheses of three modified peptide fragments of the cyclodepsipeptide didemnin B are reported. The HIP and isostatine (1st) units of the didemnin B macrocycle were simplified to a Z-alanine residue and the ester linkage (through threonine of the tetrapeptide) was replaced with amide linkages through the amines of glycine, D-alanine and an ethylenediamine linker. The latter permitted the attachment of a N-Me-D-Leu-Pro-Lac moiety to afford analogs 2, 3 and 4 respectively.

Notes

Glycine amide and alanine amide were synthesized from their corresponding N-protected carboxylic acids. Treatment of the preactivated (isobutyl chloroformate) carboxylic acid with NH₃(g) followed by deprotection afforded the amides.