Bergeron-Brlek Milan, Meanwell Michael, Britton Robert
Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada V7G 1S2.
Nat Commun. 2015 Apr 23;6:6903. doi: 10.1038/ncomms7903.
Iminosugars have attracted increasing attention as chemical probes, chaperones and leads for drug discovery. Despite several clinical successes, their de novo synthesis remains a significant challenge that also limits their integration with modern high-throughput screening technologies. Herein, we describe a unique synthetic strategy that converts a wide range of acetaldehyde derivatives into iminosugars and imino-C-nucleoside analogues in two or three straightforward transformations. We also show that this strategy can be readily applied to the rapid production of indolizidine and pyrrolizidine iminosugars. The high levels of enantio- and diastereoselectivity, excellent overall yields, convenience and broad substrate scope make this an appealing process for diversity-oriented synthesis, and should enable drug discovery efforts.
亚氨基糖作为化学探针、分子伴侣和药物发现的先导化合物，已引起越来越多的关注。尽管在临床上取得了一些成功，但其从头合成仍然是一个重大挑战，这也限制了它们与现代高通量筛选技术的整合。在此，我们描述了一种独特的合成策略，该策略通过两到三个简单的转化步骤，将多种乙醛衍生物转化为亚氨基糖和亚氨基-C-核苷类似物。我们还表明，该策略可以很容易地应用于快速生产吲哚里西啶和吡咯里西啶亚氨基糖。高对映选择性和非对映选择性、优异的总收率、便利性和广泛的底物范围，使这一过程成为一个有吸引力的多样化合成方法，并有望推动药物发现工作。
