Synthesis of new L-ascorbic ferulic acid hybrids

A feasibility and chemical study of the coupling conditions of L-ascorbic acid with ferulic acid derivatives are described on the basis of the known synergistic effects of mixtures of various antioxidants. Novel L-ascorbic ferulic hybrids linked at the C-3 hydroxyl group were prepared with the aim to protect the alcohol function and the enediol system.     

Effect of the β-propiolactone treatment on the adsorption and fusion of influenza A/Brisbane/59/2007 and A/New Caledonia/20/1999 virus H1N1 on a dimyristoylphosphatidylcholine/ganglioside GM3 mixed phospholipids monolayer at the air-water interface

The production protocol of many whole cell/virion vaccines involves an inactivation step with β-propiolactone (BPL). Despite the widespread use of BPL, its mechanism of action is poorly understood. Earlier work demonstrated that BPL alkylates nucleotide bases, but its interaction with proteins has not been studied in depth. In the present study we use ellipsometry to analyze the influence of BPL treatment of two H1N1 influenza strains, A/Brisbane/59/2007 and A/New Caledonia/20/1999, which are used for vaccine production on an industrial scale. Analyses were conducted using a mixed lipid monolayer containing ganglioside GM3, which functions as the viral receptor. Our results show that BPL treatment of both strains reduces viral affinity for the mixed monolayer and also diminishes the capacity of viral domains to self-assemble. In another series of experiments, the pH of the subphase was reduced from 7.4 to 5 to provoke the pH-induced conformational change of hemagglutinin, which occurs following endocytosis into the endosome. In the presence of the native virus the pH decrease caused a reduction in domain size, whereas lipid layer thickness and surface pressure were increased. These observations are consistent with a fusion of the viral membrane with the lipid monolayer. Importantly, this fusion was not observed with adsorbed inactivated virus, which indicates that BPL treatment inhibits the first step of virus-membrane fusion. Our data also indicate that BPL chemically modifies hemagglutinin, which mediates the interaction with GM3.     

Dehalogenation of α -haloketones and vic-dibromides with nickel boride

α-Haloketones and $\text{vic}$-dibromides are converted to the corresponding ketones and alkenes respectively with nickel boride generated $\text{in situ}$ from sodium borohydride and nickel chloride.     

Pyrrolothienopyrazines: Synthèse de la pyrrolo[1,2-a]thieno[3,2-e]pyrazine et de la pyrrolo[1,2-a]thieno[2,3-e]pyrazine

The synthesis of pyrrolo[1,2-α]thieno[3,2-e]pyrazine and pyrrolo[1,2-α]-thieno[2,3-e]pyrazine is described. These syntheses could be achieved by intramolecular cyclization of 2- (and 3-) (1-pyrrolyl)-3- (and -2)-thienyl-amines obtained by hydrolysis of carbamates or by cleavage of the corresponding ureas. An original way giving better results was also studied via a Curtius rearrangement by reaction between the azide and aldehyde groupings. The synthesis of 2- (and -3)-2-formyl-1-pyrrolyl)-2- (and -3)-thenoylazide is described.     

An efficient two-step total synthesis of the quaterpyridine nemertelline

Regioselective and univocal Suzuki cross-coupling reactions performed on halopyridinyl boronic acids provide a flexible and versatile route to a multigram scale synthesis of 2,2'-dichloro-3,4'-bipyridine 14, which allows couplings with excess pyridin-3-yl boronic acid to give a new and efficient two-step rapid synthesis of nemertelline, the quaterpyridine neurotoxin isolated from a Hoplonemertine sea worm.     

A novel synthesis of methyl cis-(3-thienyl)glycidate with 2-aminothiophenol and the synthesis of [1,5]benzothiazepine derivatives

The synthesis of cis-2,3-dihydro-3-hydroxy-2-(3-thienyl)[1,5]benzothiazepin-4(5H)-one derivatives is described starting from 2-aminothiophenol and methyl cis-(3-thienyl)glycidate. The structures were confirmed by ¹H-nmr spectroscopy.     

Molecular design based on 3D pharmacophores. Applications to 5-HT7 receptors

A definition of a pharmacophore for the 5-HT7 antagonists was carried out by searching the common chemical features of selective antagonists from the literature. A molecular design is described by analyzing the differences between this new pharmacophore and three other 3D serotonin pharmacophores previously described. This comparison led to the synthesis of a new series of potent 5-HT7 antagonists.