S-9-(2,3-二羟丙基)腺嘌呤类似物的合成及其对S-腺苷-L-高半胱氨酸水解酶的抑制活性

SYNTHESIS OF S-9-(2,3-DIHYDROXYPROPYL)ADENINE (DHPA) ANALOGS AND THEIR INHIBITION OF S-ADENOSYL-L-HOMOCYSTEINE (SAH) HYDROLASE

摘要: 为了寻找高效、低毒的抗病毒剂,本文通过用腺嘌呤及嘧啶碱基与3-氯-2-甲基丙烯缩合合成6个DHPA类似物的中间体5a,5b,6～8a和8b。应用OsO₄催化,在N-甲基吗琳-N-氧化物氧化下对烯键进行邻位双羟化,合成了5个DHPA类似物1～4a,b。对化合物5a,5b,6～8a,8b的¹HNMR数据进行了初步总结。对4个DHPA类似物测定了它们对S-腺苷-L-高半胱氨酸水解酶(SAH)的抑制活性,其中化合物1的IC₅₀为1.1mmol·L^-1,其余化合物均无抑制活性。

Abstract: In order to search for new antiviral agents with high potency and low toxicity, eleven new acyclonucleosides were synthesized. Nucleic acid bases were condensed with 3-chloro-2-methylpropene to give 5～8a.b, which were oxidized by N-methylmorpholine N-oxide in the presence of OsO₄ to give vicinal dihydroxy acyclonucleosides 1～4a.b. Four DHPA analogs have been tested for the inhibitory activities on s adenosyl L homocysteine hydrolase (SAH). Only compound 1 showed some enzyme inhibitory effect with IC 50 of 1.1 mmol·L^-1.