Beilstein J. Org. Chem.2024,20, 220–227, doi:10.3762/bjoc.20.22
analogues through the incorporation of alternative building blocks at different stages of synthesis.
Keywords: chemical glycosylation; lipid II; peptidoglycan; polyprenyls; total synthesis; Introduction
Lipid II (Figure 1) is an essential bacterial glycolipid involved in peptidoglycan biosynthesis [1]. It
a more viable strategy in contrast to other methodologies, as it offers the potential to generate ample quantities of lipid II analogues suitable for high-throughput screening endeavors. In recent years, a major focus of the Cochrane lab has been the chemical synthesis of bacterial polyprenyls to
study the mechanism of action of antimicrobial peptides that kill bacteria through binding to these polyprenyls [21][28][29][30][31][32][33][34]. Lipid II has been of particular interest, and during our synthesis of multiple different lipid II analogues, we have developed several optimizations, which we
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Graphical Abstract
Figure 1:
Structure of lipid II, with variable positions shown in red and antimicrobial-binding motifs highli...
Beilstein J. Org. Chem.2017,13, 845–854, doi:10.3762/bjoc.13.85
prevent accumulation of the desired lead structures [33].
Isoprenyl diphosphate formation
Downstream of precursor formation condensation of IPP and DMAPP to longer-chain polyprenyls precedes subsequent metabolization to linear or mono- and polycyclic products, respectively, by the terpene synthases [24
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Graphical Abstract
Scheme 1:
Isoprenoid biosynthetic pathways and examples for their engineering in heterologous production syst...