Design and Synthesis of Novel 1′,3′-Dioxolane 5′-Deoxyphosphonic Acid Purine Analogues as Potent Antiviral Agents

• Published in: Nucleosides, nucleotides & nucleic acids Vol. 31; no. 2; pp. 85 - 96
• Main Authors: Kim, Eunae, Liu, Lian Jin, Lee, Wonjae, Hong, Joon Hee
• Format: Journal Article
• Language: English
• Published: PHILADELPHIA Taylor & Francis Group 01.02.2012; Taylor & Francis
• Subjects: 1′,3′-dioxolanyl nucleoside phosphonic acid; Antiviral agent; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Biochemistry & Molecular Biology; Cell Line, Tumor; Cytomegalovirus - drug effects; Dioxolanes - chemistry; Dioxolanes - pharmacology; Dose-Response Relationship, Drug; Drug Design; Guanine Nucleotides - chemistry; Guanine Nucleotides - pharmacology; Herpesvirus 1, Human - drug effects; Herpesvirus 2, Human - drug effects; HIV-1 - drug effects; Humans; Life Sciences & Biomedicine; Microbial Sensitivity Tests; Molecular Conformation; Science & Technology; Stereoisomerism; Structure-Activity Relationship; Vorbruggen reaction; NUCLEOTIDE ANALOGS; PHOSPHONATE ANALOGS; NUCLEOSIDES; REVERSE-TRANSCRIPTASE; 1 ',3 '-dioxolanyl nucleoside phosphonic acid; Antiviral agent; Vorbruggen reaction
• ISSN: 1525-7770; 1532-2335
• DOI: 10.1080/15257770.2011.643849

Electronic parameters of 1′,3 ′-oxygen play significant roles in steering the conformation of nucleoside phosphonic acid analogues. To investigate the relationship of two oxygen atoms with antiviral enhancement, novel 1′,3 ′-dioxolane 5 ′-deoxyphosphonic acid purine analogues were synthesized via de novo acyclic stereoselective route from acrolein and glycolic acid. The synthesized nucleoside phosphonic acid analogues 14 and 19 were subjected to antiviral screening against several viruses, such as HIV-1, HSV-1, HSV-2, and HCMV. The guanine analogue 19 exhibits in vitro anti-HIV-1 activity similar to that of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) in MT-4 cells.