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阿昔洛韦(2)为高效抗病毒药,口服时对单纯性疱疹病毒感染方面疗效很高,但由于它在胃肠道未能完全吸收导致血浓度较低,影响了对许多病毒的作用。应用前体药物原理设计的6-脱氧阿昔洛韦(7),具有水中的溶解度大且在细胞内易被黄嘌呤氧化酶氧化成阿昔洛韦的优点,克服了原有的缺点。本文报道了由1a(为鸟嘌呤合成阿昔洛韦的中间体)制备7和选择性脱去O-乙酰基生成N~2-乙酰基阿昔洛韦(3)。1a和经选择性脱N-乙酰基的1b经磷酰氯氯化分别得4a和其N~2-脱乙酰相应物4b,经催化转移氢解脱
Acyclovir (2) is a highly effective antiviral agent that is highly effective in the treatment of herpes simplex virus infection when administered orally but low in blood concentration due to its incomplete absorption in the gastrointestinal tract affects the effects on many viruses . The 6-deoxy acyclovir (7) designed by using the prodrug principle has the advantages of high solubility in water and easily oxidized to acyclovir in the cells by xanthine oxidase, and overcomes the existing defects. This paper reports the preparation of 7 from 1a (an intermediate for the synthesis of acyclovir from guanine) and the selective removal of O-acetyl to N-2-acetyl acyclovir (3). 1a and selectively de-N-acetyl 1b are chlorinated with phosphoryl chloride to give 4a and its N ~ 2-deacetylated counterpart 4b, respectively, which are cleaved off by catalytic transfer of hydrogen