Synthesis of Pseudo-herpotrichone C and Structure-Activity Relationship Study of Herpotrichone-Based Inhibitors against Neuroinflammation.

We report the synthesis of pseudo-herpotrichone C and structure-activity relationship (SAR) studies of herpotrichone-based anti-neuroinflammatory agents. A streamlined route employing methoxylative bromination and dual catalytic XAT-mediated elimination enabled access to pseudo-herpotrichone C. SAR studies revealed that C4-C19 stereochemistry, C16-C18 arrangement, and C3 substitution of the herpotrichone framework collectively govern the neuroprotective activity. Notably, synthetic derivatives 4 and 5 inhibited LPS-induced nitric oxide production more strongly than natural herpotrichones A and B.