1‐Thiacyclooct‐4‐yne (=5,6‐Didehydro‐3,4,7,8‐tetrahydro‐2H‐thiocin), and Its Sulfoxide and Its Sulfone

Abstract

Abstract1‐Thiacyclooct‐4‐yne (=5,6‐didehydro‐3,4,7,8‐tetrahydro‐2H‐thiocin; 9) can be prepared from thiocan‐5‐one (6) in three steps by applying the so‐called selenadiazole method. The heterocyclic alkyne can be oxidized to the corresponding sulfoxide 16 and sulfone 17. Due to their geometrical strain, all three cyclic alkynes show high reactivities in DielsAlder and 1,3‐dipolar cycloadditions. Moreover, tetrathiafulvalenes can be prepared from 9 and 16 by the reaction with CS2.

A click-and-release approach to CO prodrugs

“…As such, we decide to take advantage of certain click reactions that we have been exploring to trigger CO release from carbonyl containing molecules, resulting in a "click and release" (CNR) prodrug system for CO. Tetraphenylcyclopentadienone (TPCPD, 1, Scheme 1) and similar molecules (dienones) are known to undergo inverse electron demand Diels-Alder reactions (DAR inv ). 46 Under the right conditions, the ketone carbonyl group is released in the form of carbon monoxide due to strain energy and thus serves as a way to "cage" CO. However, such literature reactions do not occur to an appreciable degree under physiological conditions and thus are not suitable for applications under physiological conditions.…”

“…In 2013, there was one report of using a strained alkyne (thiocyclooctyne) for similar cycloadition reactions in the exploration of new organic reactions for synthetic applications. 46 The reaction took overnight to complete at high mM conditions, and thus would not allow for the release of CO at a high enough rate/concentration for therapeutic applications, for which we need the reactions that have half lives on the scale of minutes at 37 o C at mid-µM to mid-mM concentrations. Specifically, the reaction between TPCPD (1) and BCN (2) was examined.…”