Natural‐Like Spirocyclic Δ<sup>α,β</sup>‐Butenolides Obtained from Diazo Homophthalimides
Dmitry Dar’in, Grigory Kantin, Evgeny Chupakhin, Vladimir V. Sharoyko, Mikhail Krasavin
Abstract
Abstract α‐Diazo homophotalimides were reacted with various propiolic acids on Rh 2 (esp) 2 catalysis. The resulting propiolate esters were transformed into novel, heterocyclic Δ α,β ‐spirobutenolides in good to excellent product yields. The approach represents a fundamentally novel entry into natural‐like Δ α,β ‐spirobutenolides present in many biologically active natural products as well as fully synthetic compounds endowed with diverse biological activities. The Δ α,β ‐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 50 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.