【药物名称】ONO-BB-039-02
化学结构式(Chemical Structure):
参考文献No.565880
标题:New orally active enkephalinase inhibitors: Their synthesis, biological activity, and analgesic properties
作者:Senokuchi, K.; Nakai, H.; Nagao, Y.; Sakai, Y.; Katsube, N.; Kawamura, M.
来源:Bioorg Med Chem 1998,6(4),441
合成路线图解说明:

Chiral resolution of protected dl-thiopropionic acid derivative (I) is performed by first condensation with (1R,2S)-(-)-2-amino-1,2-diphenyl ethanol in acetonitrile followed by diastereomer separation and finally hydrolysis of the optically active salt to afford the desired stereoisomer (S)-(II). Activation of (S)-(II) with oxalyl chloride in dichloromethane and subsequent coupling to L-isoglutamine derivative (III) in CH2Cl2 in the presence of pyridine provides amide (S)-(IV), which is finally converted into the target product by alkaline hydrolysis with LiOH in THF.

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