Immobilization of aluminum chloride on MCM-41 as a new catalyst system for liquid-phase isopropylation of naphthalene

A great deal of effort has been made at searching for alternative catalysts to replace conventional Lewis acid catalyst aluminum trichloride (AlCl3). In this paper, immobilization of AlCl3 on mesoporous MCM-41 silica with and without modification was carried out. The catalytic properties of the immobilized catalyst systems for liquid-phase isopropylation of naphthalene were studied and compared with those of H/MCM-41 and H/mordenite. The structures of the surface-immobilized aluminum chloride catalysts were studied and identified by using solid-state magic angle spinning nuclear magnetic resonance (MAS NMR), Fourier transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), nitrogen adsorption, and X-ray diffraction (XRD) techniques. The catalytic activity of the immobilized catalysts was found to be similar to that of acidic mordenite zeolite. A significant enhancement in the selectivity of 2,6-diisopropylnaphthalene (2,6-DIPN) was observed over the immobilized aluminum chloride catalysts. Immobilization of aluminum chloride on mesoporous silica coupled with surface silylation is a promising way of developing alternative catalyst system for liquid-phase Friedel-Crafts alkylation reactions. (C) 2002 Elsevier Science B.V. All rights reserved.

A convergent solution-phase synthesis of the macrocycle Ac-Phe-[Orn-Pro-D-Cha-Trp-Arg], a potent new antiinflammatory drug

Relatively few cyclic peptides have reached the pharmaceutical marketplace during the past decade, most produced through fermentation rather than made synthetically. Generally, this class of compounds is synthesized for research purposes on milligram scales by solid-phase methods, but if the potential of macrocyclic peptidomimetics is to be realized, low-cost larger scale solution-phase syntheses need to be devised and optimized to provide sufficient quantities for preclinical, clinical, and commercial uses. Here, we describe a cheap, medium-scale, solution-phase synthesis of the first reported highly potent, selective, and orally active antagonist of the human C5a receptor. This compound, Ac-Phe[Orn-Pro-D-Cha-Trp-Arg], known as 3D53, is a macrocyclic peptidomimetic of the human plasma protein C5a and displays excellent antiinflammatory activity in numerous animal models of human disease. In a convergent approach, two tripeptide fragments Ac-Phe-Orn-(Boc)-Pro-OH and H-D-Cha-Trp(For)-Arg-OEt were first prepared by high-yielding solution-phase couplings using a mixed anhydride method before coupling them to give a linear hexapeptide which, after deprotection, was obtained in 38% overall yield from the commercially available amino acids. Cyclization in solution using BOP reagent gave the antagonist in 33% yield (13% overall) after HPLC purification. Significant features of the synthesis were that the Arg side chain was left unprotected throughout, the component Boe-D-Cha-OH was obtained very efficiently via hydrogenation Of D-Phe with PtO2 in TFA/water, the tripeptides were coupled at the Pro-Cha junction to minimize racemization via the oxazolone pathway, and the entire synthesis was carried out without purification of any intermediates. The target cyclic product was purified (>97%) by reversed-phase HPLC. This convergent synthesis with minimal use of protecting groups allowed batches of 50100 g to be prepared efficiently in high yield using standard laboratory equipment. This type of procedure should be useful for making even larger quantities of this and other macrocyclic peptidomimetic drugs.

Thermal stability analysis of organo-silicates, using solid phase microextraction techniques

An analysis of thermal degradation products evolved during the melt processing of organo-layered silicates (OLS) was carried out via the use of a solid phase microextraction (SPME) technique. Two commerical OLSs and one produced in-house were prepared for comparision. The solid phase microextraction technique proved to be a very effective technique for investigating the degradation of the OLS at a specific processing temperature. The results showed that most available OLSs will degrade under typical conditions required for the melt processing of many polymers, including thermoplastic polyurethanes. It is suggested that these degradation products may lead to changes in the structure and properties of the final polymer, particularly in thermoplastic polyurethanes, which seem significantly succeptable to the presence of these products. It is also suggested that many commercially available OLSs are produced in such a way that results in an excess of unbound organic modifier, giving rise to a greater quantity of degradation products. All OLSs where compared and characterised by TGA and GC-MS. (c) 2004 Elsevier B.V. All rights reserved.