Bioisostere of valtrate, anti-HIV principle by inhibition for nuclear export of Rev

Rational design by the MO calculation disclosed 5,6-dihydrovaltrate (2) as the bioisostere of valtrate (1), the Rev-export inhibitor with anti-HIV activity. The synthesis of 2 was accomplished by ingenious use of asymmetric Diels–Alder reaction and stereoselective epoxidation associated with the adjacent hydroxyl group. Because of similar biological potency to 1, the analog 2 should be recognized as a promising scaffold for new anti-HIV agents with an unprecedented mechanism of action, inhibition for nuclear export of Rev protein, in the conventional remedy.

Graphical abstractBased on the design from the MO calculation, 5,6-dihydrovaltrate (2) was synthesized and revealed to be the bioisostere of valtrate (1) showing anti-HIV activity by inhibition for nuclear export of Rev.Figure optionsDownload full-size imageDownload as PowerPoint slide