J. A. Lepoivre

Synthests and Biological Evaluation of a Series of Substituted-2-Pyridine-C-Nucleosides. Part II

Abstract A cyclistation reaction of the D-allo- and D-altro isomers of 2-(2, 4:3, 5′-di-O-benzylidenepentitol-1-yl)pyridine derivatives to afford the corresponding substituted 2-(D-ribofuranosyl) pyridine-C-nucleosides, was investigated. The latter compounds were obtained in good yield (90%) if the reaction was performed in 1 N HCI. The structures were confirmed by 13C-NMR studies and an HPLC method with was developed specifically for a determination of their purity. All compounds were evaluated for biological activity in a variety of antiviral and antitumor cell systems in vitro.

Synthesis and biological evaluation of 4-carbamoyl-2-β-D-ribofuranosyl-pyridine

Abstract D-Allo/D-altro 2-(2,4:3, 5-di-O-benzylidenepentitol-1-y1)-4-(4,4-dimethyloxazolin-2-y1)pyridine was synthesized from 2-lithio-4-(4,4-dimethyloxazolin-2-y1)pyridine and 2, 4:3,5-di-O-benzylidenealdehydo-D-ribose. After mesylation and subsequent treatment of the adduct with CF3COOH/H2O and then ammonia, 4-carbamoyl-2-D-ribofuranosylpyridine was formed. The α- and β-anomers were separated by semipreparative hplc on a LICHROSORB 10 DIOL column. The β-anomer had no antiviral activity, but it had modest cytostatic activity against tumor cells.

Synthesis and biological evaluation of some D-xylofuranosyl-pyridine C-nucleosides

Abstract The addition reaction of either 3-bromo-5-lithiopyridine (2a) or 3-cyano-5-lithiopyridine (2b) to 2,4:3,5-di-O-benzylidene-aldehydo-D-xylose (1) gave a D-gulo/D-ido mixture of respectively 3-bromo- and 3-cyano-5-(2,4;3,5-di-O-benzylidene-pentitol-1-yl)pyridine (3a, b). Mesylation of C-1′ followed by reaction with CF3COOH/H2O resulted in the formation of the corresponding D-xylo-furanosyl pyridine C-nucleosides. 3-Cyano-5-D-xylofuranosylpyridine (5b) was converted to 3-carbamoyl-5-D-xylofuranosylpyridine (6) with Amberlite IRA 400 (OH−). The D-xylofuranosyl C-nucleosides were evaluated for their antiviral and cytostatic activity. No significant activity was found.

Ring-size effects in horse liver alcohol dehydrogenase-catalyzed redox reactions

Abstract For the four- to the nine-membered cycloalkanone-cycloalkanol pairs, the equilibria, reduction rates, and oxidation rates of the horse liver alcohol dehydrogenase (HLAD)-catalyzed redox reaction are determined. Depending on the ring size, the equilibria lie more or less extremely to the cycloalkanone side. The equilibria and the reduction rates of the cycloalkanones show the same characteristic dependence on the ring-strain differences between ketones and alcohols. The oxidation rates do not show this dependence which only increase for increasing ring sizes. The conclusion is that two main effects control the rates of HLAD-catalyzed redox reactions on cyclic substrates: ring-strain differences between the substrate and a cycloalkanol-like transition state, and hydrophobic interactions between the substrates and a hydrophobic substrate-binding pocket.

Synthesis and Biological Evaluation of 3-Chloro-4-(D-Ribofuranosyl)-Pyridine and 3-(D-Ribofuranosyl)-2- Pyridone

Abstract Condensation of 2-fluoro-3-lithio pyridine and 3-chloro-4-lithio pyridine with 2,4:3,5-di-O-benzylidene-alde-hydo-D-ribose gives the corresponding D-allo- and D-altro-addition products. These were converted into the corresponding mesylates and cyclized to the ribofuranosyl nucleosides with an overall yield of 60–70 %. Both nucleosides did not show any inhibitory effect on L-1210-cells.

Synthesis and Biological Evaluation of a Series of Substituted Pyridine-C-Nucleosides. Part V: 3-Chloro-4-(D-Ribofuranosyl)Pyridine and 3-(D-Ribofuranosyl)-2-Pyridone

Abstract The total synthesis of 3-chloro-4-(D-ribofuranosyl)-pyridine and 3-(D-ribo-furanosyl)-2-pyridone was elaborated using the appropriate lithiopyridines and 2,4:3,5-di-O-benzylidene-aldehydo-D-ribose. The conformation of these compounds was investigated by 360 MHz 1H-NMR. The compounds were evaluated as α,β-mixtures for their antiviral and cytostatic properties. However, no significant biological activity was found.

HLAD IMMOBILIZATION IN POLYACRYLAMIDE GELS

The immobilization of horse liver alcohol dehydrogenase in a cross-linked acrylamide-N,N1-methylenebisacrylamide copolymer gel is described. The influence of monomer concentration, the degree of cross-linking and the polymerization technique on enzyme entrapment is studied. A bead-polymerization process produced the most useful and stable immobilized enzyme preparations.

Synthesis of some pyridine-C-nucleosides

Abstract The synthesis of 4-carbamoyl-2-(2′-deoxy-β-D-ribofuranosyl)pyridine (IOβ) was accomplished using a new sugar derivative and the appropriate lithiopyridine derivative.

Approach to the Synthesis of 2-(D-Ribofuranosyl)-Pyridine Compounds

Abstract A series of pyridine C-nucleosides was synthesised by reaction of lithio pyridines with 2, 4; 3, 5-di-benzylidene-D-ribose in the initial step.

Investigation of the Synthesis of 2-Carbamoylmethyl-6-D-Ribofuranosylpyridine

Abstract During the course of our study on the synthesis of new pyridine-C-nucleosides with potential anti-viral and/or anti-tumourai properties, the preparation of 2-carbamoylmethyl-6-β-D-ribofuranosylpyridine 1, by means of a lithiation reaction on 2-(2,3-0-isopropylidene-β D-nbofuranosyl)-6-methylpyridine 2, was investigated (Scheme I). The latter compound was prepared by treating 6-methyl- toluenesulphonic acid. 2-(& D-ribofuranosyl)pyridine 1 2 with 2.2-dimethoxypropane in the presence of p-