A Scrutiny on the Reductive Amination of Carbonyl Compounds Catalyzed by Homogeneous Rh(I) Diphosphane Complexes

Abstract: The reductive amination of a series of aldehydes with secondary amines and H 2 in the presence of a homogeneous Rh-diphosphane catalyst was studied in order to establish a general mechanism of this reaction and to identify conditions for the improvement of the amine/alcohol ratio in the product. Several possible intermediates as constituents of changing equilibria like half-aminals, N,Oacetals and aminals were observed in the reaction mixture by means of 1 H NMR spectroscopy. In individual trials, these compounds could be successfully hydrogenated under the conditions applied for reductive amination (50 bar H 2 pressure, MeOH). Some evidence is accumulated that half-aminals and N,O-acetals might be key intermediates of the reductive amination. Moreover, it was found that the formation of the undesired product alcohol is likely based on the reduction of the starting carbonyl compound. However, due to numerous equilibria consisting of several intermediates, general conclusions are hard to be drawn. Proof will be given that, in several cases, the efficiency of the reductive amination of aliphatic aldehydes can be significantly improved by prehydrogenation of the cationic [Rh(dppb)(COD)] complex

Combinatorial approach towards synthesis of 2',3'-dideoxynucleosides and enzyme-catalysed selective hydrolysis of diethyl acetamidomalonate and amides of polyacetoxy aromatic carboxylic acid

507-512Seventeen noveI 3’-alkylthio-2’,3’-dideoxynucleosides have been synthesised by Michael-type addition of alkylthiols to an ,α,β-unsaturated hexose aldehyde, followed by acetylation, nucleoside coupling and deprotection. Based on these results, a general scheme for combinatorial synthesis of libraries of 3’-substituted 2’,3’-dideoxynucleosides has been proposed. Porcine pancreatic lipase (PPL) has been found to hydrolyse the amides of polyacetoxyaromatic carboxylic acids in a highly chemoselective fashion. The enzyme exclusively hydrolyses the ester group over the amide group. Hydrolysis of diethyl acetamidomalonate in phosphate buffer in the presence of α-chymotrypsin proceeds enantioselectively affording the (+)-monoacid

Modification of the length and structure of the linker of N(6)-benzyladenosine modulates its selective antiviral activity against enterovirus 71

Very recently, we demonstrated that N(6)-isopentenyladenosine, a cytokinin nucleoside, exerts a potent and selective antiviral effect on the replication of human enterovirus 71. The present study is devoted to the structure optimization of another natural compound: N(6)-benzyladenosine. We mainly focused on the exploration of the size and nature of the linker between the adenine and the phenyl ring, as well as on the necessity of the D-ribose residue. More than 30 analogues of N(6)-benzyladenosine were prepared and their antiviral properties were evaluated. Two main methodologies were used for preparation: N(6)-acetyl-2',3',5'-tri-O-acetyladenosine can be regioselectively alkylated either by alkyl halides under base promoted conditions or by alcohols in Mitsunobu reactions. After deacylation with 4 M PrNH2 in MeOH at room temperature for one day, the desired products were obtained in overall high yields. Analysis of the structure-activity relationship clearly shows that the optimal size of the linker is limited to 2 or 3 atoms (compounds 4-7). 2'-Deoxyadenosine derivatives did not elicit any inhibitory or cytotoxic effect, while 5'-deoxynucleosides still induced some cell protective antiviral activity. Based on these observations, it can be hypothesized that there may be another mechanism that is at the base of the antiviral activity of these compounds against enterovirus 71 besides a possible 5'-triphosphorylation followed by a putative inhibitory effect on RNA synthesis.publisher: Elsevier articletitle: Modification of the length and structure of the linker of N6-benzyladenosine modulates its selective antiviral activity against enterovirus 71 journaltitle: European Journal of Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.ejmech.2016.01.036 content_type: article copyright: Copyright © 2016 Elsevier Masson SAS. All rights reserved.status: publishe