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

Membrane Anchoring and Intervesicle Transfer of a Derivative of the Antibiotic Moenomycin A

“…Though elusive, the latter is prone to insertion reactions in the presence of olefins or alkynes. [1,5,6] Upon simply replacing KOH by [NEt 4 ][OH] with the aim to obtain highly concentrated solutions of the hydroxy-carbonyl adduct for a 13 C NMR investigation, we were surprised to observe that CO 2 evolution was becoming significant at room temperature, and occurred at rates apparently depending both on the nature of the counterion and the concentration.…”

“…1996, 118, 4723. [5] For an example of fluoride-ion-catalyzed reaction of allylsilanes with aldehydes, see a) A. Hosomi, A. Shirahata, H. Sakurai, Tetrahedron Lett. 1978, 3043; see also b) E. Nakamura, M. Shimizu, I. Kuwajima, J. Sakata, K. Yokoyama, R. Noyori, J. Org.…”

“…[5] It is assumed that they compete with the subtrate(s) of the transglycosylation reaction for a binding site at the enzyme, most probably for the binding site of the growing peptidoglycan chain (the glycosyl donor). [5] The oligosaccharide part of the moenomycin-type transglycosylase inhibitors is recognized with high selectivity by the enzyme. [4] However, there is another prerequisite for antibiotic activity: membrane anchoring of the antibiotic through its lipid part.…”

Moenomycin-Mediated Affinity Purification of Penicillin-Binding Protein 1b

“…[3] The structure ± activity relationship of the moenomycins has been studied extensively, [6] and a mechanism for their mode of action has been proposed. [7,8] It is assumed that they are anchored to the cytoplasmic membrane through the moenocinol lipid part, followed by highly selective recognition of the oligosaccharide moiety at a substrate binding site of the enzyme, most probably the binding site of the growing glycan chain (the glycosyl donor). Whereas the mechanism of the transpeptidation reaction is reasonably understood, the active site of the transglycosylase is still unknown and the mechanism of the transglycosylation step is largely unexplored.…”

Der lange Weg zur ersten Totalsynthese von Moenomycin A

“…[21] Anhand der Struktur-Wirkungs-Beziehungen ist postuliert worden, dass die Lipidkette der Antibiotika zunächst unselektiv mit der Cyctoplasmamembran wechselwirkt und dass dann eine hochselektive Erkennung des Kohlenhydrat-(Trisaccharid-)Teils an der Donorbindungsstelle des Enzyms erfolgt. Ein detailliertes Bild des Wirkungsmechanismus [22] ist mit jüngst publizierten Ergebnissen von Röntgenkristallstruktur-analysen bestens im Einklang. [23] Die Synthesearbeiten zu Moenomycin [8] gipfelten kürzlich in der ersten Totalsynthese von Moenomycin A durch Kahne und Mitarbeiter.…”