Synthesis and structural study of a fully protected α-C-galactosyl model dipeptide

Summary The synthesis of three N-alkyl-6,7-dideoxy-1,2:3,4-di-O-isopropylidene-7-[(alkyl-carbonyl)amino]-L-glycero-α-D-galacto-octopyranuronamides6a-c, analogous model dipeptides containing two amide groups connected to the α-carbon bearing the fully protected galactose as a side chain, has been realized with the aim of determining the conformational influence of the galactosyl moiety on the peptide backbone. Molecular modeing of6a, X-ray crystallography of6c and IR and NMR experiments on6a-c in organic solvents show that the carbohydrate ring assumes a twist boat conformation. In non-polar organic solvents, the NH of the left amide group interacts with one ketal oxygen of the galactosyl group.     

Synthesis and structural study of a fully protected α-C-galactosyl model dipeptide

The synthesis of three N-alkyl-6,7-dideoxy-1,2:3,4-di-O-isopropylidene-7-[(alkyl-carbonyl)amino]-L-glycero--D-galacto-octopyranuronamides6a–c, analogous model dipeptides containing two amide groups connected to the -carbon bearing the fully protected galactose as a side chain, has been realized with the aim of determining the conformational influence of the galactosyl moiety on the peptide backbone. Molecular modeling of 6a, X-ray crystallography of 6c, and IR and NMR experiments on 6a–c in organic solvents show that the carbohydrate ring assumes a twist boat conformation. In non-polar organic solvents, the NH of the left amide group interacts with one ketal oxygen of the galactosyl group.     

Synthesis and structural analysis of vinylogous peptides

A Z- or E-ethenyl group has been inserted between the -carbon andthe carboxyl group of the proline residue by stereoselective Hornersynthesis. The resulting vinylogous amino acid has been coupled with aminocompounds by classical methods, and model amino acid derivatives anddipeptides containing a Z- or E-CH=CMe group have been investigated insolution by ¹H-NMR and IR spectroscopy, and in the solid stateby X-ray diffraction. The E-ethenyl group gives rise to an openconformation and the Z-conformer to a folded structure with anintramolecular hydrogen bond closing a nine-membered pseudocycle.     

Synthesis of insect pheromones: Improved method for the preparation of queen substance and royal jelly of honeybees Apis mellifera

The biological activity of pheromones stems from various applications, especially in the area of pest control and insect monitoring; however, the quantity of pure pheromones available from natural sources is often extremely limited, because individual insects contain only minute amounts of pheromone. As our contribution to the field of pheromone synthesis, here we present a novel approach for the preparation of two known pheromones, namely queen substance and royal jelly of honeybees Apis mellifera. Our method is based on the original applications of lithiated α-alkenylphosphoramido anions as excellent synthetic equivalents of homoenolate anions.     

Investigation of new potent KDO-8-phosphate synthetase inhibitors

A total synthesis of (Z,E)-D-Glucophosphoenolpyruvate and its carboxylic ester derivatives is described in four or five steps from 2,3:5,6-Di-O-isopropylidene-4-O-t-butydimethylsilyl-D-glucose.     

Stereoselective synthesis and glycosidase inhibitory activity of 3,4-dihydroxy-pyrrolidin-2-one, 3,4-dihydroxy-piperidin-2-one and 1,2-dihydroxy-pyrrolizidin-3-one

3,4-Dihydroxy-pyrrolidin-2-one, 3,4-dihydroxy-piperidin-2-one and 1,2-dihydroxy-pyrrolizidin-3-one have been synthesized, using a simple strategy based on the asymmetric dihydroxylation of vinylogous aminoesters and subsequent mild intramolecular cyclization. All these compounds show a partial inhibition of alpha-glucosidase, but were inactive towards other glycosidases.     

Anti-CeHV1 antibodies of two cynomolgus macaques cross-react with HSV2 but not HSV1 antigens in ELISA

BACKGROUND: The aim of the study was to compare the cross-reactivity of macaque anti-CeHV1 antibodies with type 1 and type 2 human herpes simplex viruses (HSV1 and HSV2). METHODS: We studied the serum of 344 animals which had been tested either positive (n = 39) or negative (n = 305) for the presence of CeHV1 antibodies by expert laboratories. Macaque serums were studied by means of two ELISA: one based on HSV1 antigen-coated wells, the other on polystyrene beads coated with HSV1 and HSV2 antigens in approximately equal proportions. RESULTS: In the serum of two animals originating from Vietnam, we found anti-CeHV1 antibodies cross-reacting with HSV2 but not with HSV1 antigens. For the serum with the highest titer, inhibition by soluble antigens confirmed the high affinity of the antibodies for HSV2 antigens. CONCLUSIONS: Tests using HSV1 and HSV2 in a combined way are better suited to macaque screening than tests using only HSV1 antigens.     

Incorporation of vinylogous scaffolds in the C-terminal tripeptide of substance P.

Glycine-9 and leucine-10 of substance P (SP) are critical for (NK)-1 receptor recognition and agonist activity. Propsi(Z)-CH=CH(CH3)-CONH)Leu (or Met) and Propsi((E)-CH=CH(CH3)-CONH)Leu (or Met) have been introduced in the sequence of SP, in order to restrict the conformational flexibility of the C-terminal tripeptide, Gly-Leu-Met-NH2, of SP. Propsi((Z)-CH=C(CH2CH(CH3)2)-CONH)Met-NH2, with an isobutyl substituent to mimic the Leu side-chain, was also incorporated in place of the C-terminal tripeptide. The substituted-SP analogs were tested for their affinity to human NK-1 receptor specific binding sites (NK-1M and NK-1m) and their potency to stimulate adenylate cyclase and phospholipase C in Chinese Hamster ovary (CHO) cells transfected with the human NK-1 receptor. The most potent SP analogs [Pro9psi((Z)CH=C(CH3)CONH)Leu10]SP and [Pro9psi ((E)CH=C(CH3)CONH)Leu10]SP, are about 100-fold less potent than SP on both binding sites and second messenger pathways. These vinylogous (Z)- or (E)-CH=C(CH3)- or (Z)-CH=C(CH2CH(CH3)2) moieties hamper the correct positioning of the C-terminal tripeptide of SP within both the NK-1M- and NK-1m-specific binding sites. The origin of these lower potencies is related either to an incorrect peptidic backbone conformation and/or an unfavorable receptor interaction of the methyl or isobutyl group.     

Inclusion complexes of N-sulfamoyloxazolidinones with beta-cyclodextrin

A study of inclusion complexes of six N-sulfamoyloxazolidinone derivatives with beta-cyclodextrin is described. The inclusion complexes were prepared in solution and in solid state with stoichiometry host-guest 1:1, and characterized. In solution, the complexation was carried out by spectrophotometric measurements at 25 degrees C. The stoichiometries and stability constants of complexes at various pHs have been determined using second-derivative spectrophotometry UV-vis. Hydrophobic properties of N-sulfamoyloxazolidinones are improved following their inclusion into beta-CD.