开发两步法制备 3-PBC 和 βCCt，这两种药物在啮齿动物和灵长类动物模型中均能有效对抗酒精自我给药。
Development of a two-step route to 3-PBC and βCCt, two agents active against alcohol self-administration in rodent and primate models.
机构信息
Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, United States.
出版信息
J Org Chem. 2011 Jun 3;76(11):4721-7. doi: 10.1021/jo200425m. Epub 2011 May 4.
Abstract
To gain access to 3-propoxy-β-carboline hydrochloride (3-PBC·HCl) (1·HCl) and β-carboline-3-carboxylate-tert-butyl ester (βCCt) (2), potential clinical agents active against alcohol self-administration, a two-step route was developed. This process involves a palladium-catalyzed Buchwald-Hartwig coupling and an intramolecular Heck reaction. This two-step route provides rapid access to multigram quantities of 3-PBC (1) and βCCt (2), as well as analogues for studies of alcohol self-administration. The overall yield of 3-PBC (1) was improved from 8% to 50% by this route.
摘要
为了获得 3-丙氧基-β-咔啉盐酸盐（3-PBC·HCl）（1·HCl）和β-咔啉-3-羧酸叔丁酯（βCCt）（2），这两种有希望的临床药物可以对抗酒精自我给药，开发了一种两步法。该过程涉及钯催化的 Buchwald-Hartwig 偶联和分子内 Heck 反应。该两步法可以快速获得多克数量的 3-PBC（1）和βCCt（2），以及用于酒精自我给药研究的类似物。通过该路线，3-PBC（1）的总收率从 8%提高到 50%。
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