Department of Chemistry and Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37235, United States.
J Org Chem. 2021 Jun 18;86(12):7904-7919. doi: 10.1021/acs.joc.0c03069. Epub 2021 Jun 7.
A reinvestigation into the macrocyclooligomerization (MCO) of a tetradepsipeptide is reported, uncovering a paradox in which the MCO of depsipeptide monomers can produce "impossible" ring sizes: a 12-atom chain produced the expected 24-membered ring, alongside unexpected 18- and 30-membered cyclic oligomeric depsipeptides (CODs). We report an alternative preparation of authentic 18- and 36-membered macrocycles for this case using a stepwise synthesis that provides definitive analytical characterization for each ring size. Our investigation yields a recharacterization and reassignment of two macrocycles originally reported in this MCO series, along with updated yields and isothermal titration calorimetry data after implementation of new critical protocols for purification and subsequent analysis. Initial studies to probe this mechanistic conundrum are described.
本文重新研究了四肽的大环寡聚（MCO）反应，揭示了一个悖论，即通过二肽单体的 MCO 可以产生“不可能”的环大小：一条 12 个原子的链产生了预期的 24 元环，同时还产生了意想不到的 18 元和 30 元环状寡肽（COD）。我们报道了使用分步合成的方法来制备该情况下的真正 18 元和 36 元大环，为每个环大小提供了明确的分析表征。我们的研究对这一系列 MCO 中最初报道的两个大环进行了重新表征和重新分配，并在实施新的关键纯化和后续分析方案后更新了产率和等温滴定量热数据。描述了对这一机制难题的初步研究。
