Department of Chemistry , Imperial College London, Molecular Sciences Research Hub, White City Campus , Wood Lane , London W12 0BZ , U.K.
Pfizer Medicinal Sciences , 445 Eastern Point Road , Groton , Connecticut 06340 , United States.
J Org Chem. 2019 May 3;84(9):5943-5956. doi: 10.1021/acs.joc.9b00613. Epub 2019 Apr 19.
New small-ring derivatives can provide valuable motifs in new chemical space for drug design. 3-Aryl-3-sulfanyl azetidines are synthesized directly from azetidine-3-ols in excellent yield by a mild Fe-catalyzed thiol alkylation. A broad range of thiols and azetidinols bearing electron-donating aromatics are successful, proceeding via an azetidine carbocation. The N-carboxybenzyl group is a requirement for good reactivity and enables the NH-azetidine to be revealed. Further reactions of the azetidine sulfides demonstrate their potential for incorporation in drug discovery programs.
新的小环衍生物可以为药物设计提供有价值的新化学空间结构。通过温和的铁催化硫醇烷基化反应，可直接从氮杂环丙烷-3-醇出发，以优异的收率得到 3-芳基-3-硫基氮杂环丁烷。带有供电子芳基的各种硫醇和氮杂环丙烷醇都能成功反应，通过氮杂环丙烷碳正离子进行反应。N-羧基苄基是获得良好反应性的必要条件，并使氮杂环丙烷中的 NH 得以显露。氮杂环丁烷硫醚的进一步反应表明它们在药物发现计划中的应用潜力。
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