Use of substituted N,N'-acylbisazoles for the synthesis of ribonucleoside-5'-polyphosphates

Abstract

A series of N,N¢-acylbisazoles were used to synthesize nucleoside-5¢-polyphosphates, with target product yields which were 10 -15% higher than when unsubstituted N,N¢-acylbisazoles were used.The role of nucleoside-5¢-polyphosphate analogs as inhibitors of a variety of ATP-and GTP-dependent enzymes is well known. We studied the possibility of synthesizing nucleoside-5¢-polyphosphates using a series of substituted N,N¢-acylbisazoles. Published reports include descriptions of the successful use of N,N¢-carbonylbisazoles to activate nucleotide phosphate groups. Activated nucleoside-5¢-phosphoimidazolides are used as intermediate compounds in preparing various dinucleoside-5¢,5¢-phosphodiesters, nucleoside diphosphate sugars, and nucleoside-5¢-triphosphates [1,2]. Interest in the synthesis of these compounds persists as a result of studies of their substrate properties for different DNA polymerases of viral, bacterial, and animal origin [3].The aim of the present work was to investigate the relationship between the reactivity of N,N¢-acylbisazoles and the structures of their azole fragments. Studies were performed on, as an example, the synthesis of ribonucleoside-5¢-polyphosphates, i.e., nucleoside-5¢-phosphoazolides, methylene analogs of P 1 ,P 4 -bis-(nucleoside-5¢)tetraphosphates, and nucleoside-5¢-triphosphates, using substituted N,N¢-acylbisazoles, which have not previously been used for this purpose. The general pathway of the synthesis of these compounds is shown in Scheme 1. EXPERIMENTAL SECTIONThe IR spectra of compounds I -V were recorded using an IKS-29 instrument for samples in KBr tablets. The UV spectra of compounds I -V, nucleoside-5¢-triphosphates 310 0091-150X/10/4406-0310

Pulmonary vasculature directed adenovirus increases epithelial lining fluid alpha-1 antitrypsin levels

“…Human embryonic kidney 293 (HEK293) cell lines (Microbix Biosystems, Ontario, Mississauga, Canada), including the 293-F28 cell line, comprising a previously described derivative of HEK293 that stably express Ad5 wild-type fiber [8], were propagated in Dulbecco's modified Eagle's medium supplemented with 10% (v/v) fetal calf serum, L-glutamate (2 mM) and streptomycin (100 μg/ml). Cells were propagated at 37°C in a humidified atmosphere of 5% CO 2 .…”