New neplanocin analogues.: 12.: Alternative synthesis and antimalarial effect of (6′R)-6′-C-methylneplanocin A, a potent AdoHcy hydrolase inhibitor
New neplanocin analogues.: 12.: Alternative synthesis and antimalarial effect of (6′R)-6′-C-methylneplanocin A, a potent AdoHcy hydrolase inhibitor
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DOI：
10.1021/jm010374i
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发表时间：
2002-01-31
影响因子：
7.3
通讯作者：
Matsuda, A
中科院分区：
文献类型：
--
作者：
Shuto, S;Minakawa, N;Matsuda, A
(6'R)-6'-C-methylneplanocin A (RMNPA, 2) 是一种有效的 S-腺苷-L-高半胱氨酸 (AdoHcy) 水解酶抑制剂，通过螯合控制立体选择性添加 MeTiCl3 到 neplanocin A 6'-醛衍生物 6 中，开发了一种改进的合成方法。化合物 2 在体外和体内均有效抑制疟疾寄生虫的生长。 2对小鼠伯氏疟原虫的抗疟EC50值为1.0mg/kg/天，优于氯喹（EC50=1.8mg/kg/天）。
An improved method for the synthesis of (6'R)-6'-C-methylneplanocin A (RMNPA, 2), a potent S-adenosyl-L-homocysteine (AdoHcy) hydrolase inhibitor, was developed via a chelation-controlled stereoselective addition of MeTiCl3 to the neplanocin A 6'-aldehyde derivative 6. Compound 2 effectively inhibited the growth of malaria parasites both in vitro and in vivo. The antimalarial EC50 value of 2 against Plasmodium berghei in mice was 1.0 mg/kg/day, which was superior to that of chloroquine (EC50 = 1.8 mg/kg/day).