Solid-phase synthesis of 2,3-diphenylpropionic acid library as VLA-4 antagonists

2,3-Diphenylpropionic acid library for VLA-4 antagonist was synthesized on solid-phase. Comparison of the two synthetic routes via an orthogonal generation of two aromatic amino functional groups are discussed. From this work, several compounds were identified as potent VLA-4 antagonists.     

A modified Ortega method to evaluate the activation energies of solid state reactions

The application of the average linear integral isoconversional method developed by Ortega for evaluating the activation energies of solid state reactions may be hindered by experimental noise and the uncertainties associated with selecting appropriate reaction segments. This paper suggests a procedure, called the modified Ortega method, which can avoid or minimize these hindrances. By applying the modified Ortega method to the kinetic analyses of both simulated and experimental data, a more consistent dependence of the activation energy on the extent of reaction conversion was found with those calculated from the modified Vyazovkin method and the Friedman method.     

Reactions of Sterically Protected 1-Halo- and 1-Pseudohalo-2-Phosphaethenyl-Lithiums

Abstract

Phosphorus analogs of alkylidenecarbenoid, Ar-P=C(X)Li, where X equals halogen or pseudohalogen atom, such as C1, Br, or SPh, have been generated by use of the 2,4,6-tri-t-butylphenyl group (abbreviated to Ar in the Scheme) as a protecting group for low coordinated organophosphorus compounds. The reaction with methyl iodide and with some aldehydes or ketones, at low temperature, gave the corresponding alkylation products^[l]. The reaction with copper salts gave 1,4-diphosphabutadiene (1) or 1,4-diphosphabutatriene (2), depending upon the substituent X^[2,3], as well as reaction conditions, such as reaction tenlperature and time, solvent, presence or absence of oxygen. Upon warming the phosphaethenyllithiun1s, thus generated, the chloro derivative of E-configuration gave a phosphaalkyne (3) via [1,2]-aromatic migration^[4], whereas the bromo derivative of Z-configuration gave a l-phospha-3,4-dihydronaphthalene derivative (4), that is a formal C-H insertion product of a phosphinidenecarbene intermediate^[5].     

Semiempirical Pm3 Quantum Mechanics Calculations of Carbohydrate Crystals

ABSTRACT

Miniature crystal models of six small carbohydrates were examined using the PM3 semiempirical quantum mechanics method. The minicrystal structures, consisting of 27 sugar residues, were optimized by the combined procedure of partial optimization and reconstruction of the model, while maintaining the original crystal symmetries. All of the minicrystals were successfully optimized without exhibiting a great increase in an energy at any reconstruction step. Some minicrystals showed a prolonged behavior of optimization cycles. A major source of structure change appeared to arise from hydroxyl group rotations wherein the largest movements mostly occurred in an early optimization stage. No significant deformations in geometry of either residues or hydrogen bonds were observed in the final minicrystal structures. The thermodynamic values calculated for the optimized minicrystals were in reasonably good agreement with the literature data. The present study indicated that the PM3 semiempirical method successfully predicted the basic features of intermolecular hydrogen bonding involved in a condensed system.     

Determination of structures of cobalt(II)-chloro complexes in hydrochloric acid solutions by X-ray absorption spectroscopy at 298 K

The anion exchange reaction is fundamental to the adsorption and desorption of a specific species from a solution phase to an extracting phase, and it is widely used for separation and waste fluid treatment in industrial fields. However, the details of the anion exchange reaction are poorly understood. Quantitative thermodynamic analysis needs a precise solution condition before and after the exchange reaction. Identification of species adsorbed on the anion exchanger is also necessary because there are multiple species in the solution phase in general. Cobalt is a base metal that is widely used in modern society. One of the authors determined the distribution of cobalt-chloro complexes in hydrochloric acid solutions. It is necessary to know what species are adsorbed on anion exchangers for the thermodynamic analysis of the anion exchange reaction. The comparison in structures between the species in the solution phase and adsorbed on anion exchangers reveals what species are adsorbed. Therefore, the determination of the structures of cobalt-chloro complexes in the solution phase is the next step for quantitative analysis. X-ray absorption spectroscopy (XAS) was used for the structure analysis. Factor analysis can decompose extended X-ray absorption fine structure (EXAFS) and X-ray absorption near-edge structure (XANES) spectra consisting of multiple species into individual spectra of single species using the distribution determined using UV-Vis absorption spectra. Fitting EXAFS theoretical models to the decomposed individual spectra determined the structures of three cobalt-chloro complexes: an octahedron of [Co^II(H₂O)₆]²⁺, a distorted octahedron of [Co^II(H₂O)₅Cl]⁺, and a tetrahedron of [Co^IICl₄]^2?. The XANES spectra showed us that the Cl ligand in [Co^II(H₂O)₅Cl]⁺ was attracted to the center atom of Co^II by an electrostatic force, and the bonding system between Cl ligands and Co^II in [Co^IICl₄]^2? involved covalency.

     

Synthesis of pyrido[1′,2′:1,2]imidazo[4,5-b]quinoxalines

Synthesis of pyrido[1′,2′:1,2]imidazo[4,5-b]quinoxalines by the facile cyclizations of 2,3-dichloroquinoxalines with 2-aminopyridines and of 2-amino-3-chloroquinoxalines with various substituted pyridines is described.     

Synthesis of optically inactive cellulose via cationic ring-opening polymerization

Cellulose, which comprises D-glucose and L-glucose (D,L-cellulose), was synthesized from D-glucose (1D) and L-glucose (1L) via cationic ring-opening polymerization. Specifically, the ring-opening copolymerization of 3-O-benzyl-2,6-di-O-pivaloyl-β-D-glucopyranoside (2D) and 3-O-benzyl-2,6-di-O-pivaloyl-β-D-glucopyranoside (2L), synthesized from compounds 1D and 1L, respectively, in a 1:1 ratio, afforded 3-O-benzyl-2,6-di-O-β-D,L-glucopyranan (3DL) with a degree of polymerization (DPn) of 28.5 (Mw/Mn?=?1.90) in quantitative yield. The deprotection of compound 3DL and subsequent acetylation proceeded smoothly to afford acetylated compound 4DL with a DPn of 18.6 (Mw/Mn?=?2.08). The specific rotation of acetylated compound 4DL was?+?0.01°, suggesting that acetylated compound 4DL was optically inactive cellulose triacetate. Furthermore, before acetylation, compound 4DL was an optically inactive cellulose comprising an almost racemic mixture of D-glucose and L-glucose. Compound 4DL was an amorphous polymer. This is the first reported synthesis of optically inactive D,L-cellulose.