Ring formation in a pentapeptide with alternating L and D residues: an analogy to cyclization in the biosynthesis of peptide antibiotics.

Acetylation of L-isoleucyl-D-alanyl-D-alanyl-L-valyl-D-leucine with acetic anhydride followed by methylation with diazomethane yielded the expected acetylpentapeptide methyl ester with molecular weight 541, but also resulted in the formation of a by-product with molecular weight 555. The incorporation of the mass corresponding to CH2 seems to be due to ring closure--via a mixed anhydride--and methylation of the cyclol derivative thus formed. A preferred, ring-like conformation stabilized by intramolecular hydrogen bonds that in turn are the consequences of the alternation of D- and L- residues in the sequence, is invoked as explanation for the unexpected cyclization. This assumption is supported by the conversion of the pentapeptide methyl ester to desthiomalformain in molten imidazole.