Synthesis ofN-acetylmuramic acid derivatives as potential inhibitors of the D-glutamic acid-adding enzyme

Abstract

Compounds containing N-acetyl-D-muramic acid and (L-1-aminoethy1)phosphonic acid were designed as potential inhibitors of the D-glutamic acid-adding enzyme of the biosynthesis of bacterial peptidoglycan.)phosphonic acid dimethyl ester]-c~,P-D-glucopyranose (9) was also prepared and was submitted to the MacDonald reaction in order to introduce a phosphate group on the anomeric position. A complex mixture of phosphorylated orland methylated derivatives of 3 was obtained. They were purified by h.p.1.c. and characterized by analyses of hexosamine, amino acid and labile phosphate, and by plasma desorption mass spectrometry. Neither 3 nor its derivatives inhibited the Dglutamic acid-adding enzyme from Escherichia coli.

Second-generation sulfonamide inhibitors of d-glutamic acid-adding enzyme: Activity optimisation with conformationally rigid analogues of d-glutamic acid

“…The overall yield of this approach was very low (13%), which was mostly due to the poor conversion of 17 to 18 in the first reaction step. The title 2,4-disubstituted aniline 12i was therefore synthesised using a different approach, starting from commercially available methyl 2-amino-5-furoate (20) and methyl acrylate, following a literature procedure [40]. After DielseAlder reaction in the first step the aminosubstituted 7-oxabicyclo[2.2.1]heptene 21 was spontaneously converted to substituted aniline 22.…”

Structure and function of the Mur enzymes: development of novel inhibitors

“…As for substrate analogues, the effect of various analogues of d ‐glutamic acid on the E. coli enzyme was investigated, and a few displayed weak inhibition (Pratviel‐Sosa et al ., 1994). In addition, N ‐acetylmuramic acid derivatives were also synthesized and tested as potential inhibitors of MurD, but no promising inhibitors resulted from that approach (Auger et al ., 1995).…”

Structural and Functional Characterization of Enantiomeric Glutamic Acid Derivatives as Potential Transition State Analogue Inhibitors of MurD Ligase

“…Its high (stereo)specificity for D-glutamic acid has been shown by studying structurally related analogues tested as substrates or inhibitors. 21,22 There have been several successful attempts to identify MurD inhibitors by using the transition-state hypothesis [23][24][25][26][27][28][29] and it was suggested that D-glutamic acid represents an essential fragment of a potent inhibitor. 25,26 Based on this rationale we recently synthesized a series of sulfonamide derivatives of D-glutamic acid, as analogues of the tetrahedral intermediate (unpublished results).…”