Synthesis of a Novel Bicyclic Scaffold Inspired by the Antifungal Natural Product Sordarin
Keyword(s):
A simplified bicyclic scaffold inspired by the antifungal natural product sordarin was designed and synthesized which maintains the carboxylic acid/aldehyde (or nitrile) pharmacophore. A densely functionalized chiral cyclopentadiene was constructed in 8 steps and utilized in a Diels-Alder reaction with acrylonitrile. The resulting [2.2.1]cycloheptene was transformed into a scaffold possessing vicinal carboxylic acid and nitrile groups, with orientations predicted to provide high affinity for the fungal protein eukaryotic elongation factor 2 (eEF2).
2018 ◽
2019 ◽
1990 ◽
Vol 265
(11)
◽
pp. 6030-6034
2005 ◽
Vol 37
(1)
◽
pp. 91-99
◽