Dietrich Müller

Moenomycin A: The role of the methyl group in the moenuronamide unit and a general discussion of structure-activity relationships

Abstract Two disaccharide analogues 1b and 17a of moenomycin A have been synthesized and their antibiotic and transglycosylase-inhibiting properties have been determined. The results permit for the first time to arrive at a general view of the structural requirements in this class of compounds necessary to elicit antibiotic activity.

Synthesis of a trisaccharide analogue of moenomycin A12 Implications of new moenomycin structure-activity relationships

Abstract A trisaccharide analogue of moenomycin A, 9a, has been synthesized and has found to be antibiotically inactive. This compound differs from an active compound, 9b, solely by the exchange NHAc→OH in unit C. A binding model for moenomycin-type transglycosylase inhibitors at the enzyme penicillin binding protein is proposed.

Moenomycin a: Minimum structural requirements for biological activity

Abstract A stepwise degradation of the oligosaccharide part of moenomycin A (2) was performed. The degradation products were assayed for antibiotic activity both in vivo and in an E.coli cell-free system. Units E, F, G, H, and I haue been found to be essential for full biological ( in vitro ) activity. It is suggested that 2 is a competitive inhibitor of the peptidoglycan polymerase.

Moenomycin A: further structural studies and preparation of simple derivatives

Abstract Preparation of the moenomycin A derivatives 2 – 5 is reported. Structure 1 proposed for moenomycin A is confirmed by 13 C NMR and fast atom bombardment mass spectrometry data. Compounds 2 and 3 are antibiotically active whereas methyl derivatives 4 and 5 lack activity.

Structures of some moenomycin antibiotics-inhibitors of peptidoglycan biosynthesis

Abstract Isolation, structural assignment, and antibiotic efficiency of the new moenomycin antibiotics C3 (1b) and C4 (1c) is decribed. The previously published structure of pholipomycin (1d) is modified.

Moenomycin A - Structure-activity relations synthesis of the D-galacturonamide analogue of the smallest antibiotically active degradation product of moenomycin A

Abstract Compound 10c which is the galacturonamide analogue of 2, the smallest degradation product of moenomycin A (1) with full antibiotic activity, has been synthesized. 10c is devoid of antibiotic activity.

Some selective reactions of moenomycin A.

A number of new moenomycin A derivatives have been prepared. Their antibiotic properties highlight the very specific recognition of moenomycin A at the transglycosylase binding site which is the basis of the transglycosylase inhibiting property of moenomycin A (4a).

Moenomycin A: reactions at the lipid part. New structure-activity relations

Abstract Methods for the removal and the oxidation of the lipid moiety of the antibiotic moenomycin A have been studied. Combined with biochemical studies, the results demonstrate that antibiotic activity is closely related with the integrity of the lipid unit.

Synthesis of two structural analogues of the smallest antibiotically active degradation product of moenomycin a

Abstract The disacchande analogues 19 and 2 of moenomycin A have been synthesized. In contrast to the moenomycin A degradation product 1, synthetic conpounds 19 and 2 do not show antibiotic activity.

The first moenomycin antibiotic without the methyl-branched uronic acid constituent.- Unexpected structure activity relations

Abstract Isolation and structure elucidation of a new moenomycin antibiotic (C1, 1e) that lacks the branching methyl group in the 4-position of unit F are reported. The smallest antibiotically active degradation product of 1e is the trisaccharide derivative 3. This observation is in contrast to structure activity relations in the moenomycin A series where it was found that disaccharide 4a is fully active.