An improved, large-scale preparation is described, leading from 2-acetamido-2-deoxy-~glucose to benzyl 2-acetamido-4,6-O-benzylidene-3-O-[(R)-l-carboxyethyl]-2-deoxy-a-~glucopyranoside (a-Benzyl N-acetyl-4,6-O-benzylidenemuramic acid, 5r) and its (5')-isomer (a-Benzyl N-acetyl-4,6-O-benzylideneisomuramic acid, 5s) uia chromatographic separation of their methyl esters (4r and 4s). The high yield and complete separation of 4r and 4 s allow a reliable assessment of the low stereoselectivity of the lactyl ether synthesis step from racemic 2-chloropropionic acid. Similarly, syntheses employing pure enantiomers of 2-chloropropionic acid were disclosed as not completely stereospecific. Coupling products with L-and D-alanine esters were prepared for both 5r and 5s.
Muramylpeptide
, 1. -Stereochemisch einheitliche Derivate der Muramin-und Isomuraminsauren Eine verbesserte Synthese im grol3en MaiJstab fuhrt von 2-Acetamido-2-desoxy-~-glucose zu Benzyl-2-acetamido-4,6-O-benzylidene-3-O-[(R)-1 -carboxyethyl]-2-desoxy-a-~-glucopyranosid (cc-Benzyl-N-acetyl-4,6-O-benzylidenmuraminsiure 5r) und ihrem (S)-Isomeren (a-Benzyl-N-acetyl-4,6-O-benzylidenisomuraminsaure, 5s) iiber eine chromatographische Trennung ihrer Methylester (4r und 4s). Die hohe Ausbeute und die vollstandige Trennung von 4r und 4s erlaubt eine verlal3liche Aussage iiber die niedrige Stereoselektivitlt der Lactyletherbildung durch racemische 2-Chlorpropionsaure wahrend der Synthese. Synthesen mit Hilfe von (R)-oder (S)-Chlorpropionsgure sind ebenfalls nicht stereospezifisch. Von beiden Sauren 5r und 5s wurden Kupplungsprodukte mit L-und D-Alaninestern dargestellt.
The presence of muramic acid in bacterial cell wall peptidoglycans is well established, and structures have been elucidated for many of them '). Several groups2-') have synthesized muramyl peptide subunits of these structures and/or artificial modifications of these subunits, which exhibit biological activities, such as immunomodulation or arthritogenesis*.'). The first problem in the synthesis of muramyl peptides is the reliable supply of a stereochemically pure muramic acid