Synthesis of sulfur karrikin bioisosteres as potential neuroprotectives

Abstract

The only known sulfur-containing karrikin, 3-methyl-2H-thiopyrano[3,4-b]furan-2-one, has been recently identified as an extremely efficient neuroprotective butenolide. Herein, we report the targeted synthesis of this compound as well as new synthetic protocols toward a class of compounds derived from 2H-furo[2,3-c]pyran-2-ones (karrikins) via bioisosteric exchange of oxygen with sulfur. In particular, we present synthetic procedures toward bioisosteres of karrikins with one or two sulfur heteroatoms incorporated into the core backbone together with evaluation of their biological activity in inhibition of acetylcholinesterase.

Update on thiopyran-fused heterocycle synthesis (2013–2024)

“…The Darzens reaction of 230 yielded episulfide 231 , which underwent a Barton–Kellogg-type reaction with triphenylphosphine to yield compound 232 (Scheme 44). 67 However, it was observed that the sulfur analogues of karrikin exhibited low activity towards AChE.…”