酸促进的 N-叔丁氧羰基、N-苄基双保护的 2-氨基吡啶甲基吡咯烷衍生物的脱苄基反应
Acid-Facilitated Debenzylation of N-Boc, N-Benzyl Double Protected 2-Aminopyridinomethylpyrrolidine Derivatives.
作者信息
Ji Haitao, Jing Qing, Huang Jinwen, Silverman Richard B
机构信息
Departments of Chemistry and Molecular Biosciences, Chemistry of Life Processes Institute, and Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, Illinois 60208-3113.
出版信息
Tetrahedron. 2012 Feb 4;68(5):1359-1366. doi: 10.1016/j.tet.2011.12.013. Epub 2011 Dec 13.
Abstract
2-Aminopyridinomethyl pyrrolidines represent a class of highly potent and selective neuronal nitric oxide synthase inhibitors. Conditions for a Mitsunobu reaction of a naphthol and a hindered secondary alcohol were optimized to give good to excellent yields. A key step in the synthesis of these inhibitors is the deprotection of the benzyl group from the N-Boc and N-Bn double protected 2-aminopyridine ring at a late stage of the synthesis, which has been proven difficult in our previous syntheses. Acetic acid was found to facilitate the N-Bn deprotection.
摘要
2-氨基吡啶甲基吡咯烷类化合物是一类高效且具选择性的神经元型一氧化氮合酶抑制剂。对萘酚与位阻仲醇的 Mitsunobu 反应条件进行了优化，以获得良好至优异的产率。这些抑制剂合成中的关键步骤是在合成后期从 N-Boc 和 N-Bn 双保护的 2-氨基吡啶环上去除苄基保护，在我们之前的合成中已证明这一步很困难。发现乙酸有助于 N-Bn 的脱保护。
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