Synthesis of Cyclic and Acyclic Pyrimidine Nucleosides Analogues with Anticipated Antiviral Activity.

Emad M. El Telbani,Mohamed F. El-Shehry,Mohamed I. Hegab

doi:10.17344/acsi.2017.4144

Abstract

A convenient method for preparation of cyclic and acyclic nucleosides was achieved by alkylation of 6-(2,4-dichlorophenoxymethyl) pyrimidine-2,4-dione (1) with a variety of acyclic and cyclic activated sugar analogues, namely (2-acetoxyethoxy)methyl acetate (3), 2-(acetoxymethoxy)propane-1,3-diyl dibenzoate (4), benzyloxymethyl acetate (5), 2-acetoxy-5-(benzoyloxymethyl)tetrahydrofuran-3,4-diyl dibenzoate (12), 5-chloro-2-((4-chlorobenzoyloxy)methyl) tetrahydrofuran-3-yl 4-chlorobenzoate (13) and 2-(acetoxymethyl)-6-bromotetrahydro-2H-pyran-3,4,5-triyl triacetate (14), respectively. Deprotection of the synthesized nucleosides was achieved by using methanolic ammonia. The structures of the newly synthesized nucleoside analogues were fully characterized by analytical methods (mass spectrometry, 1H NMR, 13C NMR, and elemental analysis).

Highlights

A number of base-modified nucleosides have been playing a vital and important role as therapeutic agents in the treatment of patients infected with different viruses including human immunodeficiency virus (HIV), herpes simplex virus (HSV), hepatitis B virus (HBV), hepatitis C virus (HCV) and cytomegalovirus (CMV) infections.[1]
Our strategy to design and synthesize pyrimidine nucleoside analogues was based on the alkylation of si
The 1H NMR showed the disappearance of –NH proton which was detected in the parent compound 1 and instead a new signal appeared at the range δ 5.34–5.62 ppm characteristic for (– OCH2N) indicative for the acyclic nucleosides formation

Summary

Introduction

A number of base-modified nucleosides have been playing a vital and important role as therapeutic agents in the treatment of patients infected with different viruses including human immunodeficiency virus (HIV), herpes simplex virus (HSV), hepatitis B virus (HBV), hepatitis C virus (HCV) and cytomegalovirus (CMV) infections.[1]. It is well known that functionalized nitrogen heterocycles play an interesting role in drug chemistry and they have been intensively studied and used as scaffolds for searching and developing new drugs.[3] Pyrimidine-incorporating sugar residues represent an interesting class of nucleosides which have a promising antiviral chemotherapy potential, especially that class in which the cyclic sugar residue is replaced with open-chain “acyclic” sugar moieties. The effective method of protection and deprotection will be examined

Experimental

Results and Discussion

Conclusions