Design and Synthesis of 2΄-Azido-2΄-deoxy-4΄-selenofuranosyl Pyrimidines As Potential Antiviral Agents

Abstract

세계보건기구의 보고에 따르면 세계 인구의 3%, 즉 1억 7천만 명이 HCV에 감염되었거나 이로 인해 간경화나 간암으로 발전할 위험에 처해있다. 뉴클레오사이드는 항 바이러스와 항암효과를 나타내기 때문에 치료학적으로 유용한 구조로 사용될 수 있다. 4′-selenopyrimidine nucleosides는 D-Lyxonolactone-2,3-O-isopropylidene로부터 stereoselective하게 합성되었다. 이를 수행하는데 intramolecular relactonization와 Pummerer-type base condensation이 중요한 반응 단계로 사용되었고 4′-seleno pyrimidine의 2′ 위치에 azido기를 good to moderate yields로 regioselective하게 도입할 수 있었다 12a-c [β and α]. α- azido group은 sodium azide를 이용한 2,2′- anhydro nucleosides의 ring을 개열을 통해 도입이 가능했으며, β-azido group의 도입은 standard Mitsunobu conditions에 의해 이루어졌다.;WHO estimates that about 170 million people, 3% of the world's population, are infected with Hepatitis C Virus (HCV) and are at risk of developing liver cirrhosis and/or liver cancer. The nucleoside structure has proven to be an effective template for the development of therapeutically useful agents with antiviral and antitumor activity. For the development of new anti-HCV agents, novel 2'-azido-4'-selenofuranosyl pyrmidines were designed and synthesized from 2,3-isopropylidene-D-ribonolactone. Stereoselective syntheses of the 4'-selenopyrimidine nucleosides were accomplished from 2,3-O-isopropylidene-D-ribonolactone. The key steps of the synthetic procedure are intramolecular relactonization and Pummerer-type base condensation. The introduction of the azido group at the 2'-position of 4'-seleno pyrimidine nucleosides 12a-c was accomplished regioselectively in good to moderate yields. The α-azido group was introduced by ring opening of 2,2'-anhydro derivatives 18a-c using sodium azide, while the β-azido group was introduced under standard Mitsunobu conditions using diethyl azodicarboxylate.