Peter Welzel

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.

Moenomycin A: A structural revision and new structure-activity reactions

Abstract A detailed FAB MS analysis combined with NMR and chemical results requires the structure of moenomycin A to be revised from 1a to 1b. New bio-chemical results seem to support the assumption that in the region F-G-H of lb the structural requirements for antibiotic activity are rather strict.

Aptamers that bind to the antibiotic moenomycin A

Nuclease-resistant moenomycin-binding aptamers with dissociation constants in the range of 300 to 400 nM have been selected. Competition experiments have demonstrated that these aptamers recognize a disaccharide analogue of moenomycin. The results offer the opportunity of setting up a selective and sensitive assay for identifying moenomycin biosynthetic precursors.

Platelet activating factor synthetic studies

Abstract From the mannitol derivatives 8 and 37 both enantiomeric series of optically active glycerol derivatives are easily available as exemplified by the synthesis of known precursors of PAF (6) and ent-6.

A structurally and biogenetically interesting moenomycin antibiotic

Isolation and structure elucidation of a new moenomycin antibiotic (A12, 1a) is reported that differs from moenomycin A by lack of the branching methyl group and by the configuration at C-4 of unit F. The smallest antibiotically active degradation product of 1a is the trisaccharide derivative 3a. This observation is in contrast to structure activity relations in the moenomycin A series where it was found that disaccharide 4b is fully active. An explanation is offered for this difference.

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.

Routes to derivatives of strigol (the witchweed germination factor) modified) in the 5-position

Abstract The title compounds were prepared using nucleophilic substitution in the 5- position of 5b, 6b, 11a, and 11b or electrophilic addition to the diene system in 4 as key reactions. Methods for configurational assignment at C-5 and C-2′ are discussed.

Stimulation of Orobanche crenata Seed Germination by (+)-Strigol and Structural Analogues Dependence on Constitution and Configuration of the Germinatio Stimulants

Summary The stimulation of Orobanche crenata seed germination by (+)-strigol and a series of structurally related compounds differing from (+)-strigol in constitution and/or configuration is described. Both constitution and configuration of the stimulants influence the biological activity. The absolute configuration at C-2′ (strigol numbering) seems to be of special importance.

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.