Moenomycin has an unusual structure and is the only known inhibitor of
bacterial transglycosylases, the enzymes that are essential for the
biosynthesis of the bacterial cell wall. On a molar basis moenomycin A is
100 to a 1000 times more potent than vancomycin. The use of moenomycin as
an antibitotic has been hampered by its poor physiochemical properties
related to the phosphoglycerate lipid moiety. We recently reported the
first synthesis of moenomycin A as well as chemistry to degrade and
reconstruct the natural product. Here we report the synthesis of a set of
analogs that help us dissect components of the phosphoglycerate lipid
responsible for biological activity and enzyme binding. The results
reported provide insight into how to alter the phosphoglycerate lipid moiety
in order to better understand the minimal structural requirements for
biological activity.