The Synthesis of Novel 5′‐Deoxy‐3′,5′,5′‐trifluoro‐apiosyl Nucleoside Phosphonic Acid Analogs as Antiviral Agents

Bulletin of the Korean Chemical Society

Joon Hee Hong¹  Seyeon Kim³ 

[1] 21 Project Team, College of Pharmacy Chosun University Kwangju 501‐759 Republic of Korea;BK‐

关键词: Antiviral agents;    5′;    ‐;    Deoxy‐;    3′;    ,5′;    ,5′;    ‐;    trifluoro‐;    apiose phosphonic acid analogs;    Vorbrü;    ggen reaction;   

DOI  :  10.1002/bkcs.10478

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

Racemic syntheses of novel 5′‐deoxy‐3′,5′,5′‐trifluoro‐apiose nucleoside phosphonic acid analogs were carried out from 1,3‐dihydroxyacetone, to be used as antiviral agents. Nucleophilic displacement of the triflate intermediate with diethyl (lithiodifluoromethyl)phosphonate was performed to yield the corresponding (α,α‐difluoroalkyl) phosphonate. Condensation successfully proceeded from a glycosyl donor under Vorbrüggen conditions to yield the nucleoside phosphonate analogs. Ammonolysis and hydrolysis of the phosphonates yielded the corresponding nucleoside phosphonic acid analogs. Furthermore, the lipophilic prodrug of the adenine derivative was synthesized to increase cellular uptake. The synthesized nucleoside analogs were screened for their antiviral activity against human immunodeficiency virus (HIV)‐1. The bis(SATE) prodrug of the adenine analog exhibited significant in vitro activity against HIV‐1.

【 授权许可】

Unknown