Synthesis and shift-reagent-assisted full NMR assignment of bacterial (Z₈,E₂,ω)-undecaprenol

Abstract

The repeating isoprene unit is a fundamental biosynthetic motif. Repetitive structure presents challenges both for synthesis and for structural characterization. In this synthesis of the (Z8, E2, ω)-undecaprenol of prokaryotic glycobiology, we exemplify solutions to these challenges. Allylation of sulfone-derived carbanions controlled the stereochemistry, and its proof-of-structure was secured with Eu(hfc)3 complexation to disperse the overlayed resonances of its 1H NMR spectrum.

16-Hydroxy-Lycopersene, a Polyisoprenoid Alcohol Isolated from Tournefortia hirsutissima, Inhibits Nitric Oxide Production in RAW 264.7 Cells and Induces Apoptosis in Hep3B Cells

“…The signal at δ C 68.62 (C-16) corroborated the presence of a methine carbinol group. The configuration of the internal prenyl residues resulted to be E according to the chemical shifts of methyl carbons C-34, -35, -36, -37, -38 and -39 between δ C 16.76 and 16.17 [21]. The COSY correlations permitted the assignation of the resonances at δ H 5.36 (H-15), 2.40 and 2.26 (H-17) by crosspeaks with δ H 4.39 (H-16).…”

Mechanistic Insights into the Activities of Major Families of Enzymes in Bacterial Peptidoglycan Assembly and Breakdown

“…However, due to the scarcity of this lipid carrier in bacteria, earlier chemical syntheses of Lipid II had used (Z 7 , E 3 , ω)-undecaprenol isolated from plants instead, which is much more abundant in nature. [35] As these Lipid II analogues are well tolerated by PGTs in biochemical assays, many researchers have conveniently annotated the lipid tail of natural bacterial Lipid II as Z 7 , E 3 , ω, which is a misnomer. [35] Natural bacterial Lipid II molecules are complex and hydrophobic, which are considerably difficult to work with.…”

“…[35] As these Lipid II analogues are well tolerated by PGTs in biochemical assays, many researchers have conveniently annotated the lipid tail of natural bacterial Lipid II as Z 7 , E 3 , ω, which is a misnomer. [35] Natural bacterial Lipid II molecules are complex and hydrophobic, which are considerably difficult to work with. In efforts to search for shorter lipid surrogates, Ye et al evaluated a panel of Lipid II analogues with varying lipid tails for PGT polymerisation in vitro.…”

From plant to probe: semi-synthesis of labelled undecaprenol analogues allows rapid access to probes for antibiotic targets

“…Bacterial undecaprenol, which has the (Z 8 , E 2 , o)-configuration, is present in low amounts and is not easily isolated but (Z 7 , E 3 , o)undecaprenol can be extracted from various plant sources and is the version used in most UCG studies given its easier accessibility. 18 Herein, we describe the large-scale extraction of undecaprenol from bay leaves and its derivatization into novel labelled analogues.…”

“…Scheme 3 Synthesis of o-labelled undecaprenol analogues using S N 2 displacement reactions. Conditions: (a) HIO 4 , THF/H 2 O, 3 h, 0 1C to RT; (b) DHP, PPTS, CH 2 Cl 2 , 8 h, RT; (c) NaBH 4 , MeOH, Et 2 O, 2 h, RT, 51% over 3 steps; (d) MsCl, NEt 3 , CH 2 Cl 2 , 2 h, 0 1C; (e) KSAc, DMF, 2 h, 60 1C; (f) p-TsOH, THF/ MeOH, 18 h, RT; (g) NaN 3 , DMF, 2 h, 60 1C, yields from 16: 50% (17) and 53%(18). DHP = dihydropyran, PPTS = pyridinium para-toluenesulfonate.…”