Department of Chemistry, Imperial College London , South Kensington Campus, London SW7 2AZ, U.K.
J Org Chem. 2013 Dec 6;78(23):11646-55. doi: 10.1021/jo401316a. Epub 2013 Nov 8.
The stereochemistry of the desulfurization products of chiral natural and synthetic 3,6-epidithiodiketopiperazines (ETPs) is specified inconsistently in the literature. Qualitative mechanisms have been put forward to explain apparently divergent stereochemical pathways, but the quantitative feasibility of such mechanistic pathways has not been assessed. We report a computational study revealing that desulfurization of ETPs should occur universally with retention of configuration. While the majority of stereochemically assigned and reassigned cases fit this model, until now desulfurization of the synthetic gliotoxin analogue shown has remained assigned as proceeding via inversion of configuration. Through detailed chiroptical studies comparing experimentally obtained optical rotation values, electronic circular dichroism spectra, and vibrational circular dichroism spectra to their computationally simulated counterparts as well as chemical derivatization studies, we have unambiguously demonstrated that contrary to its current assignment in the literature, the desulfurization of this synthetic ETP also proceeds with retention of configuration.
手性天然和合成 3,6-表硫二酮哌嗪 (ETP) 的脱硫产物的立体化学在文献中描述不一致。已经提出了定性机制来解释明显不同的立体化学途径，但尚未评估这种机制途径的定量可行性。我们报告了一项计算研究，揭示了 ETP 的脱硫反应应该普遍具有构型保持。虽然大多数立体化学分配和重新分配的情况都符合该模型，但直到现在，合成Gliotoxin 类似物的脱硫反应仍然被认为是通过构型反转进行的。通过详细的手性研究，将实验获得的旋光值、电子圆二色光谱和振动圆二色光谱与其计算模拟对应物进行比较，以及化学衍生化研究，我们已经明确证明，与文献中的当前分配情况相反，这种合成 ETP 的脱硫反应也具有构型保持。
