Enantioselective synthesis of BMS-911278: a triple reuptake inhibitor

BMS-911278 was identified as a potent triple reuptake inhibitor potentially useful for the treatment of depression. The original racemic synthesis suffered from tedious and low recovery resolution and HPLC separation, as well as low-yielding hazardous N-demethylation at the API step. To support further preclinical studies, a scalable enantioselective synthesis was developed. Herein, we report an efficient asymmetric synthesis of BMS-911278 featuring two key steps: an enantioselective Miyaura reaction and an intramolecular regioselective cyclization.     

Asymmetric chemoenzymatic synthesis of N-acetyl-α-amino esters based on lipase-catalyzed kinetic resolutions through interesterification reactions

Several phenylalanine analogs have been synthesized through a four-step route starting from easily available ethyl acetamidocyanoacetate. In a first reaction, and making use of phase transfer catalysts, this compound reacted with several alkyl halides, being benzyltributylammonium chloride identified as the best one for the production of a series of quaternary amino acids in moderate to excellent yields (52–95%). Then, the corresponding N-acetyl-phenylalanine methyl and allyl ester derivatives were obtained through acidic hydrolysis, esterification, and N-acetylation. Rhizomucor miehei lipase was found as a versatile enzyme for the resolution of these amino esters, finding the best results through interesterification reactions with butyl butyrate in acetonitrile. A great influence in the stereoselectivity was found depending on the chemical structure of the compound, achieving for the non- or para-substituted in the phenyl ring excellent stereoselectivities, being moderate for the meta-nitro derivative, while the ortho-nitro amino ester did not react.     

Description of functional groups by means of domain-restricted reduced density matrices

This report constitutes an application of our previous theoretical works on partitionings of the first-order reduced density matrix according to the atomic domains defined in the theory of atoms in molecules. The numerical determinations obtained reveal that the domain-restricted reduced density matrices, which are the tools resulting from the former treatments, are suitable devices to describe chemical features of molecular fragments. We have focused attention on a study of functional groups in several series of organic compounds confirming the usefulness of these tools.     

Variation du nombre de Lefschetz dans une famille d'automorphismes analytiques

Sans résumé     

Structure-Reactivity correlations in the addition of water to aromatic substrates

The addition of water to 1-(4-Z-2,6-dinitrophenyl)-3-methylimidazolium chloride (Z = CN, NO₂, and CF₃) is catalyzed by carboxylate bases. There is a decrease in ρ with increasing basicity of the catalyst with ?ρ/?pK_BH = ?0.090. The results indicate that the mechanism of the reaction involves the addition of water to the aromatic substrates catalyzed by general bases. The changes in the structure-reactivity parameters with changing pK of the catalysts or Z in the substrate are rationalized in terms of changing bond lengths in the transition state. The activation parameters and the kinetic solvent isotopic effect were determined for the water, acetate, and OH^? catalyzed reactions and are consistent with the proposed mechanism.     

Anodic oxidation of porous silicon bilayers

This paper focuses on the study of the effect of anodic oxidation in porous silicon bilayers composed of two porous layers of different porosities. The order of the two types of layers has been alternated, and the thicknesses and refractive indices have been optically characterized by Fourier transform infrared spectroscopy. The results show that the refractive index of anodic oxidized porous silicon is reduced significantly with respect to just formed porous silicon. It is also observed that the quality of the oxidation is related to the porosity of the inner porous layer of the silicon bilayer structure. This effect is interpreted in terms of quantum size effects.     

Riccati differential inequalities and dichotomies for linear systems

A general notion of dichotomy for linear differential systems is investigated. It is well known that a system x′=A(t)x in which the matrix A(t) is bounded and diagonally dominant by rows or columns has an invariant splitting of its solution space into two subspaces each uniformly asymptotically stable, one for increasing time and the other for decreasing time. Similar results are obtained here where the concept of diagonal dominance is weakened using Riccati inequalities.