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Synthesis of Muramyl Peptides Containing meso ‐Diaminopimelic Acid
Author(s) -
Kubasch Niels,
Schmidt Richard R.
Publication year - 2002
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200208)2002:16<2710::aid-ejoc2710>3.0.co;2-8
Subject(s) - muramic acid , chemistry , diaminopimelic acid , stereochemistry , alanine , virginiamycin , tripeptide , peptidoglycan , amino acid , organic chemistry , biochemistry , antibiotics , enzyme
Chain‐extension of L ‐glutamate aldehyde 3 by means of the Wittig−Horner reaction furnished the desired C 7 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‐(2 S ,6 R )‐2,6‐diaminopimelic acid ( 45 ), muramyl‐ L ‐alanyl L ‐isoglutaminyl‐(2 S ,6 R )‐2,6‐diaminopimelinyl‐ D ‐alanine ( 47 ), 1,6‐anhydromuramyl‐ L ‐alanyl‐ D ‐isoglutaminyl‐(2 S ,6 R )‐2,6‐diaminopimelic acid ( 50a ), and 1,6‐anhydromuramyl‐ L ‐alanyl‐ D ‐isoglutaminyl‐(2 S ,6 S )‐2,6‐diaminiopimelic acid ( 50b ). (© Wiley‐VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)