Synthesis of Muramyl Peptides Containing meso-Diaminopimelic Acid

Abstract

Chain-extension of L-glutamate aldehyde 3 by means of the Wittig−Horner reaction furnished the desired C7 dicarboxylic acid derivative, which in turn, after C-C double bond hydrogenation and protecting group manipulation, afforded the 2,6-diaminopimelic acid derivatives (S,R)-9 and (S,S)-9, both with the desired orthogonal protecting group pattern. Synthesis of the muramic acid derivative 15 and attachment of an L-alanine residue furnished muramyl-L-alanine 18. The corresponding 1,6-anhydromuramic acid derivative 26 was obtained similarly. Treatment of these compounds with peptides 28−30 and with the 2,6-diaminopimelic acid containing di- and tripeptides 32a, 32b, and 35 gave the protected muramyl peptides 17, 37, 40, 42, 44, 46, and 49a and 49b, which, after deprotection, afforded the desired target molecules muramyl-L-alanine (38), muramyl-L-alanyl-D-glutamic acid (39), muramyl-L-alanyl-D-glutaminide (41), muramyl-L-alanyl-D-isoglutaminyl-L-lysine (43), muramyl-L-alanyl-D-isoglutaminyl-(2S,6R)-2,6-diaminopimelic acid (45), muramyl-L-alanylL-isoglutaminyl-(2S,6R)-2,6-diaminopimelinyl-D-alanine (47), 1,6-anhydromuramyl-L-alanyl-D-isoglutaminyl-(2S,6R)-2,6-diaminopimelic acid (50a), and 1,6-anhydromuramyl-L-alanyl-D-isoglutaminyl-(2S,6S)-2,6-diaminiopimelic acid (50b). (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)