Inhibitory Evaluation of αPMM/PGM from : Chemical Synthesis, Enzyme Kinetics, and Protein Crystallographic Study.

α-Phosphomannomutase/phosphoglucomutase (αPMM/PGM) from is involved in bacterial cell wall assembly and is implicated in virulence, yet few studies have addressed αPMM/PGM inhibition from this important Gram-negative bacterial human pathogen. Four structurally different α-d-glucopyranose 1-phosphate (αG1P) derivatives including 1--fluoromethylated analogues (-), 1,2-cyclic phosph(on)ate analogues (-), isosteric methylene phosphono analogues ( and ), and 6-fluoro-αG1P (), were synthesized and assessed as potential time-dependent or reversible αPMM/PGM inhibitors. The resulting kinetic data were consistent with the crystallographic structures of the highly homologous αPGM with inhibitors and - binding to the enzyme active site (1.

A step-wise synthetic approach is necessary to access γ-conjugates of folate: folate-conjugated prodigiosenes.

Despite the vast literature that describes reacting folic acid with a pharmacophore, this route is ineffective in providing the correct regioisomer of the resulting conjugate. We herein present a step-wise route to the preparation of nine folate conjugates of the tripyrrolic prodigiosene skeleton. The strict requirement for step-wise construction of the folate core is demonstrated, so as to achieve conjugation at only the desired γ-carboxylic acid and thus maintain the α-carboxylic site for folate receptor (FRα) recognition.

Deuteration and tautomeric reactivity of the 1-methyl functionality of free-base dipyrrins.

Regioselective reactivity of the 1-methyl group of free-base dipyrrins is explored, including discussion of tautomerism to provide exocyclic alkenyl reactivity. Deuterium is installed so as to generate dipyrrins substituted with deuterated methyl groups. Furthermore, the 1-methyl group reacts to become involved in C-C bonds involving only sp-hybridised carbon atoms.

Chiral induction at octahedral Ru(II) via the disassembly of diruthenium(II,III) tetracarboxylates using a variety of chiral diphosphine ligands.

Achiral [Ru2(μ-O2CR)4(MeOH)2](PF6) (R = CH3 or C6H5) reacts with the chiral diphosphines R,R- and S,S-Chiraphos (two chiral centers on ligand between the coordinating P atoms) and R-Prophos (one chiral center on ligand between the coordinating P atoms) leading to a disassembly of the paddlewheel core and the highly diastereoselective production of Λ-[Ru(η(2)-O2CC6H5)(η(2)-R,R-Chiraphos)2](PF6) (Λ-R,R-III), Δ-[Ru(η(2)-O2CC6H5)(η(2)-S,S-Chiraphos)2](PF6) (Δ-S,S-III) (the R = CH3 complexes of Chiraphos were reported in a earlier communication in this journal), and Λ-[Ru(η(2)-O2CCH3)(η(2)-R-Prophos)2](PF6) (Λ-R,R-VI), respectively, in high yield and purity. Reactions of the same starting material with R,R- and S,S-o-tolyl-Dipamp (chiral centers are the coordinating P-atoms) lead to an inversion in the chirality-at-metal producing Λ-[Ru(η(2)-O2CC6H5)(η(2)-S,S-o-tolyl-Dipamp)2](PF6) (Λ-S,S-IV), Δ-[Ru(η(2)-O2CC6H5)(η(2)-R,R-o-tolyl-Dipamp)2](PF6) (Δ-R,R-IV), Λ-[Ru(η(2)-O2CCH3)(η(2)-S,S-o-tolyl-Dipamp)2](PF6) (Λ-S,S-V), and Δ-[Ru(η(2)-O2CCH3)(η(2)-R,R-o-tolyl-Dipamp)2](PF6) (Δ-R,R-V). X-ray crystallography of all but Λ-S,S-V and Δ-R,R-V and solid-state circular dichroism (CD) show that only the indicated diastereomers are present in the solid-state.

Synthesis and characterisation of the unsubstituted dipyrrin and 4,4-dichloro-4-bora-3a,4a-diaza-s-indacene: improved synthesis and functionalisation of the simplest BODIPY framework.

An improved and scalable synthesis of the unsubstituted 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene framework facilitates access to the previously unreported parent dipyrrin HCl salt, as well as 4,4-dichloro-4-bora-3a,4a-diaza-s-indacene.