Total synthesis of tunicamycin

Liquid Chromatography–Electrospray Mass Spectrometry of Tunicamycin-Type Antibiotics

“…Functionally, the tunicamycin-type antibiotics are potent inhibitors of the polyprenol-P:N-acetylhexosamine-1-P translocase family and, consequently, are commonly used tools for studying protein N-glycosylation and bacterial cell wall biosynthesis (1,2). These known biological activities and the structures have been confirmed by the total synthesis of tunicamycin V (11,12).…”

Inhibitors of protein glycosylation and glycoprotein processing in viral systems

“…The mixture of homologues making up the tunicamycins differ only in the structure of the fatty acid components. The total synthesis of tunicamycin has been recently achieved (Suami et al, 1985). Tunicamycin is a UDP-GIcNAc analog, inhibiting enzymes translocating GIcNAc-1-P (or derivatives thereof) from the uridine diphosphate ester to a polyprenol phosphate (Elbein, 1984).…”

A Modular Approach to Phosphoglycosyltransferase Inhibitors Inspired by Nucleoside Antibiotics

“…This is exemplified by the large differencesi ni nhibition properties of mureidomycin Aa nd tunicamycin ( Figure 1). Furthermore, the complexity of the natural product structures makes it very challenging to repurpose the structures of the natural products, by synthesis [14][15][16] or semisynthesis, [17][18][19][20][21][22] to target alternative PGTsw ith different substrate specificities.T his challenge is furthere xacerbated when working with PGTs belongingt os tructural classes other than the wellstudied MraY and WecA-type integral membrane proteins, which feature 10 and 11 predicted TMHs, respectively.F or example,r ecent bioinformaticsa nd biochemical analysish as revealed thousands of homologous small bacterial PGTsw ith only as ingle TMH and as oluble globulard omain within a2 0-25 kDa protein. [23] While these PGTsc atalyze comparable biochemicalp rocesses and also play important roles at the initiation of diverse glycoconjugate biosynthetic pathways,t here are currently no small molecule inhibitors that can be used to inform on the biology and essentiality of particularp athways and which may ultimately representn ovel targets for therapeutic intervention.…”