Aminodiols, aminotetraols and 1,2,3-triazoles based on -gibberic acid: stereoselective syntheses and antiproliferative activities.

A new series of aminodiols, aminotetraols and 1,2,3-triazoles based on -gibberic acid were synthesized in a stereoselective manner, starting from commercially available gibberellic acid. -Gibberic acid, prepared from gibberellic acid according to a literature method, was applied to SeO/-BuOOH-mediated allylic oxidation, yielding the triol, which is a key intermediate. After protecting the 1,4-diol functionality as acetonide, epoxidation was performed using either -CPBA or -BuOOH/VO(acac) to produce the epoxy alcohol.

-quinone methide driven synthesis of kynurenic acid lactams.

Lactam formation of different KYNA amides and Mannich bases mediated by -quinone methide has been investigated. The efficiency of the two routes of the cyclization process was revealed and the influence of diverse amide side chains was explored. In this regard compounds bearing a tertiary amine function in the amide side chain resulted in the formation of the lactam product, while the formation of dimer derivatives was observed in the case of other KYNA amides.

Stereoselective synthesis and antiproliferative activity of -gibberic acid-based 1,3-aminoalcohol regioisomers.

A new library of -gibberic acid-based aminoalcohol regioisomers was synthesised stereoselectively starting from commercially available gibberellic acid, which yields -gibberic acid under mild acidic conditions. The successful formation of hydroxymethyl ketone derivative 5, by acid-mediated rearrangement of previously prepared epoxide, paved the way to obtain the desired 1,3-aminoalcohols through Schiff base formation. To obtain the desired regioisomers, the primary alcohol functionality of 5 was subjected to mesylation, then replaced with either primary amine or sodium azide.

Synthesis of the extracellular domain of GLP-1R by chemical and biotechnological approaches.

The extracellular domain of the glucagon-like peptide-1 receptor, GLP-1R, is responsible for the binding of GLP-1, and a handful of additional agonists (such as exenatide, lixisenatide, and liraglutide) used daily for treating type II diabetes mellitus. Lead discovery and optimization, however, require binding studies, which, in turn, necessitate the total synthesis of GLP-1R, comprising 108 residues. A protein domain of 10-15 kDa size could be obtained either by expression in or by ligating solid-phase peptide synthesis (SPPS)-made fragments.

Synthetic- and DFT modelling studies on regioselective modified Mannich reactions of hydroxy-KYNA derivatives.

The syntheses of hydroxy-substituted kynurenic acid (KYNA) derivatives have been achieved by an optimised Conrad-Limpach procedure. The derivatives were then reacted with morpholine and paraformaldehyde, as a representative amine and aldehyde, in a modified Mannich reaction. The newly introduced substituents altered the preferred reaction centre of the KYNA skeleton.

-Quinone Methide Driven Synthesis of New ,- or ,-Heterocycles.

To synthesize functionalized Mannich bases that can serve two different types of -quinone methide (-QM) intermediates, 2-naphthol and 6-hydroxyquinoline were reacted with salicylic aldehyde in the presence of morpholine. The Mannich bases that can form -QM and --QM were also synthesized by mixing 2-naphthol, 2-nitrobenzaldehyde, and morpholine followed by reduction of the nitro group. The highly functionalized aminonaphthol derivatives were then tested in [4+2] cycloaddition with different cyclic imines.

Homology modeling and phylogenetic relationships of catalases of an opportunistic pathogen Rhizopus oryzae.

Aims: A homology modeling methodology was developed and used to obtain the 3D structures for four putative catalases of Rhizopus oryzae in order to assess their functionality.

Main Methods: Homology models were built using different modeling strategies using non-protein compounds as steric constraints, a symmetry constraint to force identical chains and an additional loop modeling algorithm. Percent structural overlap values (SO) were calculated for each model-template pair to qualify the homology models.