Vladimir N. Barai

Synthesis of 2-Chloro-2′-Deoxyadenosine by Microbiological Transglycosylation

Abstract The title compound have been synthesized by an enzymatic trans-2′-deoxyribosylation of 2-chloroadenine using the whole cells of E. coli BMT-1D/1A as a biocatalyst and 2′-deoxyguanosine as a donor of glycosyl moiety.

Chemical and Enzymatic Synthesis and Antiviral Properties of 2′-Deoxy-2′-fluoroguanosine

Chemical and enzymatic methods were employed for the synthesis of the title compound, 2F-Guo 7. High antiviral activity of 2F-Guo was established in chick embryo cells infected with influenza virus FPV/Rostock/34 (H7N1) and herpes simplex virus (HSV) type I (1C strain).

Chemical-Enzymatic Synthesis of 3′-Amino-2′, 3′-dideoxy-β-D-ribofuranosides of Natural Heterocyclic Bases and Their 5′-Monophosphates

Abstract Treatment of O2, 3′-anhydro-5′-O-trityl derivatives of thymidine (1) and 2′-deoxyuridine (2) with lithium azide in dimethylformamide at 150 °C resulted in the formation of the corresponding isomeric 3′-azido-2′, 3′-dideoxy-5′-O-trityl-β-D-ribofuranosyl N1- (the major products) and N3-nucleosides (3/4 and 5/6). 3′-Amino-2′, 3′-dideoxy-β-D-ribofuranosides of thymidine [Thd(3′NH2)], uridine [dUrd(3′NH2)], and cytidine [dCyd(3′NH2)] were synthesized from the corresponding 3′-azido derivatives. The Thd(3′NH2) and dUrd(3′NH2) were used as donors of carbohydrate moiety in the reaction of enzymatic transglycosylation of adenine and guanine to afford dAdo(3′NH2) and dGuo(3′NH2). The substrate activity of dN(3′NH2) vs. nucleoside phosphotransferase of the whole cells of Erwinia herbicola was studied.

Enzymatic synthesis of nucleoside 5′-mono and -triphosphates

The transformation of fluorodeoxy‐nucleosides into 5‐monophosphates with the use of whole bacterial cells of Erwinia herbicola as a biocatalyst and PNP as a phosphate donor and next into 5‐triphosphates by using an extract of the Saccharomyces cerevisiae cells has been demonstrated.

Benzimidazoles in the Reaction of Enzymatic Transglycosylation

Abstract Substrate activity of a broad spectrum of derivatives of benzimidazole in the reaction of enzymatic ribo- and 2-deoxyribosylation catalyzed by purine nucleoside phosphorylase of whole cells of E. coli BMT-1D/1A has been studied. Guanosine or 2′-deoxyguanosine were used as glycosyl donors.

Microbiological synthesis of 5-ethyl- and (E)-5-(2-bromovinyl)-2′-deoxyuridine

SummaryThe title compounds were prepared by an enzymatic transdeoxyribosylation from 2′ dGuo or 2′ dThd to the respective heterocyclic bases, 5-ethyluracil and (E)-5-(2-bromovinyl)uracil, using the whole bacterial cells ofEscherichia coli as a biocatalyst.

Chemo‐Enzymatic Synthesis of 3‐Deoxy‐β‐D‐ribofuranosyl Purines

9-(3-Deoxy-β-D-erythro-pentofuranosyl)-2,6-diaminopurine (6) was synthesized by an enzymatic transglycosylation of 2,6-diaminopurine (2) with 3′-deoxycytidine (1) as a donor of 3-deoxy-D-erythro-pentofuranose moiety. This transformation comprises i) deamination of 1 to 3′-deoxyuridine (3) under the action of whole cell (E. coli BM-11) cytidine deaminase (CDase), ii) the phosphorolytic cleavage of 3 by uridine phosphorylase (UPase) giving rise to the formation of uracil (4) and 3-deoxy-α-D-erythro-pentofuranose-1-O-phosphate (5), and iii) coupling of the latter with 2 catalyzed by whole cell (E. coli BMT-4D/1A) purine nucleoside phosphorylase (PNPase). Deamination of 6 by adenosine deaminase (ADase) gave 3′-deoxyguanosine (7). Treatment of 6 with NaNO2 afforded 9-(3-deoxy-β-D-erythro-pentofuranosyl)-2-amino-6-oxopurine (3′-deoxyisoguanosine; 8). Schiemann reaction of 6 (HF/HBF4+NaNO2) gave 9-(3-deoxy-β-D-erythro-pentofuranosyl)-2-fluoroadenine (9).

An improved method for the enzymatic transformation of nucleosides into 5'-monophosphates.

An improved method to transform nucleosides into 5′-monophosphates using nucleoside phosphotransferase from Erwinia herbicola is reported. The method is based on the shift in the equilibrium state of the reaction to the formation of desired product due to its precipitation by Zn2+. Under optimal conditions, the extent of nucleoside transformations into nucleoside-5′-monophosphates were 41–91% (mol).

Chemo-enzymatic synthesis of 3-deoxy-beta-D-ribofuranosyl purines and study of their biological properties.

Abstract 9-(3-Deoxy-β-d-erythro-pentofuranosyl)-2,6-diaminopurine (2) was synthesized by an enzymatic transglycosylation of 2,6-diaminopurine using 3′-deoxycytidine (1) as a donor of the sugar moiety. Nucleoside 2 was transformed to 3′-deoxy guanosine (3), 9-(3-deoxy-β-d-erythro-pentofuranosyl)-2-amino-6-oxopurine (3′-deoxyisoguanosine; 4), and 9-(3-deoxy-β-d-erythro-pentofuranosyl)-2-fluoroadenine (5). Compounds 2–5 were evaluated for their anti-HIV activity.

Enzymatic synthesis of 2′-deoxyadenosine

SummaryThe title compound was prepared by a two step enzymatic procedure consisting of DNA hydrolysis to the mixture of 2′-deoxynucleosides followed by a transdeoxyribosilation of exogenous adenine.