Synthesis and Analysis of Bacterial Folate Metabolism Intermediates and Antifolates
Synthesis and Analysis of Bacterial Folate Metabolism Intermediates and Antifolates
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DOI：
10.1021/acs.orglett.7b02487
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发表时间：
2017-10-06
期刊：
影响因子：
5.2
通讯作者：
Aldrich, Courtney C.
中科院分区：
文献类型：
--
作者：
Dawadi, Surendra;Kordus, Shannon L.;Aldrich, Courtney C.
对氨基水杨酸（PAS）是一种用于治疗耐药结核病（TB）的药物，其作用机制已通过其活性代谢物的首次合成和生化表征得到证实。该合成的特点是由叶酸降解得到的n -2-乙酰-6-甲酰蝶呤与适当功能化的芳胺偶联形成席夫碱。亚胺和蝶呤环的连续化学选择性还原导致形成二氢叶酸类似物7和其他两种二氢叶酸。
The mechanism of action of para-aminosalicylic acid (PAS), a drug used to treat drug-resistant tuberculosis (TB), has been confirmed through the first synthesis and biochemical characterization of its active metabolite 7. The synthesis features the coupling of N-2-acetyl-6-formylpterin obtained from the degradation of folic acid and appropriately functionalized arylamines to form Schiff bases. The sequential chemoselective reduction of the imine and pterin ring led to the formation of dihydrofolate analogue 7 and two other dihydropteroate species.