Synthesis of sulfur karrikin bioisosteres as potential neuroprotectives

Beilstein J Org Chem. 2022 May 16:18:549-554. doi: 10.3762/bjoc.18.57. eCollection 2022.

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.

Keywords: acetylcholinesterase; butenolides; karrikin; sulfur.

Grants and funding

Financial support from the Czech Science Foundation (20-11571S) and Academy of Sciences of the Czech Republic (Research Plan RVO: 61388963) is gratefully acknowledged.