Chair of Natural Products Chemistry, Saint Petersburg State University, Saint-Petersburg, 199034, Russian Federation.
Immanuel Kant Baltic Federal University, Kaliningrad, 236041, Russian Federation.
Chemistry. 2021 Jun 1;27(31):8221-8227. doi: 10.1002/chem.202100880. Epub 2021 Apr 30.
α-Diazo homophotalimides were reacted with various propiolic acids on Rh (esp) catalysis. The resulting propiolate esters were transformed into novel, heterocyclic Δ -spirobutenolides in good to excellent product yields. The approach represents a fundamentally novel entry into natural-like Δ -spirobutenolides present in many biologically active natural products as well as fully synthetic compounds endowed with diverse biological activities. The Δ -spirobutenolides thus obtained were shown to inhibit thioredoxin reductase, a selenocysteine enzyme target for cancer. Moreover, for the best compound in the series (TrxR IC 1.49±0.08 μM), by using MALDI-TOF mass-spectrometry it was shown that it selectively binds selenocysteine in the presence of a 10-fold excess of cysteine. This validates the new compound as a promising lead for anticancer therapy development.
α-重氮偕二氮戊环与各种丙炔酸在铑（特别是）催化下反应。得到的丙炔酸酯在良好到优异的产率下转化为新型杂环Δ-螺环丁烯内酯。该方法代表了一种进入许多具有生物活性的天然产物以及具有多种生物活性的全合成化合物中存在的天然样Δ-螺环丁烯内酯的全新方法。所得到的Δ-螺环丁烯内酯被证明可以抑制硫氧还蛋白还原酶，这是一种硒半胱氨酸酶，是癌症的靶点。此外，在所研究的化合物系列中，最好的化合物（TrxR IC 1.49±0.08 μM），通过 MALDI-TOF 质谱分析表明，在 10 倍过量半胱氨酸存在的情况下，它可以选择性地结合硒半胱氨酸。这验证了新化合物作为抗癌治疗开发的有前途的先导化合物。
