Kurita Daiki, Sato Hajime, Miyamoto Kazunori, Uchiyama Masanobu
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 4-4-37 Takeda, Kofu, Yamanashi 400-8510, Japan.
J Org Chem. 2023 Sep 1;88(17):12797-12801. doi: 10.1021/acs.joc.3c01061. Epub 2023 Aug 13.
Epipolythiodioxopiperazines (ETPs) make up a class of biologically active fungal metabolites with a transannular disulfide bridge. In this work, we used DFT calculations to examine in detail the degradation (desulfurization) pathways of α-β/α-α bridged ETPs. The chemical stability of ETPs is influenced by the type of sulfur bridge, the structural features, and the storage conditions. Our results suggest appropriate protection of the phenolic OH of ETPs would improve various pharmaceutically relevant properties, including bioavailability.
表硫代二氧哌嗪（ETPs）是一类具有跨环二硫键的生物活性真菌代谢产物。在这项工作中，我们使用密度泛函理论（DFT）计算详细研究了α-β/α-α桥连ETPs的降解（脱硫）途径。ETPs的化学稳定性受硫桥类型、结构特征和储存条件的影响。我们的结果表明，对ETPs的酚羟基进行适当保护将改善包括生物利用度在内的各种与药学相关的性质。
