Efficient synthesis of 5′-O(N)-carbamyl and -polycarbamyl nucleosides

A simple and efficient method for the preparation of 5′-O(N)-carbamyl and 5′-O(N)-polycarbamyl nucleoside derivatives is reported. The method consisted of treatment of 2′,3′-O-protected purine (Ado, Ino) or pyrimidine nucleosides (Thd, Urd) with trichloroacetylisocyanate, followed by cleavage of the trichloroacetyl moiety by silica-gel promoted methanolysis during column chromatography. Iterative application of this method gave mono, di, and tricarbamyl derivatives in good to excellent yields (ave = 80%).     

Zero-order release formulations using a novel cellulose ester

New carboxymethylcellulose esters were developed with useful properties for oral dosage forms in drug delivery. Normally, commercial cellulose esters are used as the major excipients in oral dosage forms as a coating or a membrane. In applications involving compression tablets, cellulose esters are usually mixed with other more hydrophilic matrix components to facilitate dissolution of the active. In the present study, novel cellulose esters were single component matrix resins. Pharmaceutical actives were cryogenically ground as a physical blend or an amorphous blend with the polymer. Subsequently, tablets were made by direct compression using a single tablet press, or capsules were made by filling them with the ground material. Dissolution tests were completed on the solid dosage forms at pH 1.2, 4.5, 6.8 or 7.4 in a United States Pharmacopeia (USP) II device to determine the release profiles for up to 24 h. Carboxymethylcellulose esters provide an excellent matrix for controlling both the rate of release and the pH at which pharmaceutical actives release into the aqueous environment. When used in suitable quantities, dictated by the active of interest, carboxymethylcellulose acetate butyrate provided zero-order release over sustained time up to 24 h.     

Tunneling in the 1,5-hydrogen shift reactions of 1,3-cyclopentadiene and 5-methyl-1,3-cyclopentadiene

MPW1K/6-31+G(d,p) calculations which include the effects of small curvature tunneling find that, around room temperature, thermally activated tunneling dominates the 1,5-hydrogen shift reactions of 1,3-cyclopentadiene (2a) and 5-methyl-1,3-cyclopentadiene (2c). The calculated temperature dependence of the H/D kinetic isotope effect (KIE) for the latter rearrangement agrees well with experimental measurements that were published nearly 40 years ago. It is argued that the experimental KIEs provide prima facie evidence for tunneling in this reaction. The calculations also predict that it should be possible, at least in principle, to confirm this conclusion by observing curvature in the Arrhenius plot for the rearrangement of 2c.     

Oxidation of tertiary silanes by osmium tetroxide

In the presence of an excess of pyridine ligand L, osmium tetroxide oxidizes tertiary silanes (Et(3)SiH, (i)Pr(3)SiH, Ph(3)SiH, or PhMe(2)SiH) to the corresponding silanols. With L = 4-tert-butylpyridine ((t)Bupy), OsO(4)((t)Bupy) oxidizes Et(3)SiH and PhMe(2)SiH to yield 100 +/- 2% of silanol and the structurally characterized osmium(VI) mu-oxo dimer [OsO(2)((t)Bupy)(2)](2)(mu-O)(2) (1a). With L = pyridine (py), only 40-60% yields of R(3)SiOH are obtained, apparently because of coprecipitation of osmium(VIII) with [Os(O)(2)py(2)](2)(mu-O)(2) (1b). Excess silane in these reactions causes further reduction of the OsVI products, and similar osmium "over-reduction" is observed with PhSiH(3), Bu(3)SnH, and boranes. The pathway for OsO(4)(L) + R(3)SiH involves an intermediate, which forms rapidly at 200 K and decays more slowly to products. NMR and IR spectra indicate that the intermediate is a monomeric Os(VI)-hydroxo-siloxo complex, trans-cis-cis-Os(O)(2)L(2)(OH)(OSiR(3)). Mechanistic studies and density functional theory calculations indicate that the intermediate is formed by the [3 + 2] addition of an Si-H bond across an O=Os=O fragment. This is the first direct observation of a [3 + 2] intermediate in a sigma-bond oxidation, though such species have previously been implicated in reactions of H-H and C-H bonds with OsO(4)(L) and RuO(4).     

Coexistence of superconductivity and long-range antiferromagnetic order in the compound ErxMo6Se8

Low temperature specific heat and magnetic susceptibility measurements indicate that superconductivity and long-range antiferromagnetic order coexist in the compound Er_xMo₆Se₈ (x = 1.0 and 1.2).     

Measurement of the pressure dependence of Tc for superconducting spinel compounds

The superconducting transition temperatures (T_c) of CuRh₂Se₄, CuRh₂S₄ and LiTi₂O₄ were all found to increase linearly under hydrostatic pressure up to 22 kbar, at a rate of 1–5 × 10^-5 Kbar^-1. These results are discussed in terms of the dependence of T_c on Debye temperature previously found for this set of compounds from heat capacity measurements at zero pressure.     

BOOK REVIEW

Fishing for Truth: A Sociological Analysis of Northern Cod Stock Assessments from 1977 to 1990, A.C. Finlayson, Published by the Institute of Social and Economic Research, Memorial University of Newfoundland, 1994, 176 pp., ISBN 0-919666-79-5