Preparation and reactivity of biomass-derived dihydro-dioxins

This work was supported by EPSRC PhD studentships EP/1654168 (JRDM) and EP/1518175 (DMMB) and the Industrial Biotechnology Innovation Centre (DMMB).The depolymerisation of the biopolymer lignin can give pure aromatic monomers but selective catalytic approaches remain scarce. Here, an approach was re-routed to deliver an unusual phenolic monomer. This monomer’s instability proved challenging but a degradation study identified strategies to overcome this. Heterocycles and a useful synthetic intermediate were prepared. The range of aromatics available from the b-O-4 unit in lignin was extended.PostprintPeer reviewe

Synthesis and Structural Revision of the Fungal Tetramic Acid Metabolite Spiroscytalin

Spiroscytalin, a natural 3-spirotetramic acid of hitherto uncertain absolute configuration, was synthesized for the first time by a one-pot Knoevenagel–IMDA reaction of an l-phenylalanine-derived tetramic acid and (<i>R</i>)-2-methyl-deca-6<i>E</i>,8<i>E</i>-dienal. Its absolute configuration was assigned by the known configurations of the starting compounds and by NOESY correlations. Its identity with the natural isolate was proved by the comparison of the NMR and circular dichroism spectra and of the specific optical rotations. Its absolute configuration (3<i>R</i>,5<i>S</i>,6<i>S</i>,7<i>R</i>,11<i>S</i>,14<i>R</i>) is enantiomeric to that originally proposed by the isolating group. This natural isomer of spiroscytalin showed moderate activity against Candida albicans and good activity against an export-deficient mutant of Escherichia coli

Next generation glucose-1-phosphate thymidylyltransferase (RmlA) inhibitors : an extended SAR study to direct future design

Funding: This work was supported by grants from The Scottish Universities Life Science Alliance (L.P., Ph.D. studentship), a China Scholarship Council-University of St Andrews PhD Fellowship (GX). JHN is funded by the Wellcome Trust (100209/Z/12/Z).The monosaccharide L-Rhamnose is an important component of bacterial cell walls. The first step in the L-rhamnose biosynthetic pathway is catalysed by glucose-1-phosphate thymidylyltransferase (RmlA), which condenses glucose-1-phosphate (Glu-1-P) with deoxythymidine triphosphate (dTTP) to yield dTDP-D-glucose. In addition to the active site where catalysis of this reaction occurs, RmlA has an allosteric site that is important for its function. Building on previous reports, SAR studies have explored further the allosteric site, leading to the identification of very potent P. aeruginosa RmlA inhibitors. Modification at the C6-NH2 of the inhibitor’s pyrimidinedione core structure was tolerated. X-ray crystallographic analysis of the complexes of P.aeruginosa RmlA with the novel analogues revealed that C6-aminoalkyl substituents can be used to position a modifiable amine just outside the allosteric pocket. This opens up the possibility of linking a siderophore to this class of inhibitor with the goal of enhancing bacterial cell wall permeability.Publisher PDFPeer reviewe