Concise synthesis of 5,6-dihydrovaltrate leading to enhanced Rev-export inhibitory congener

The concise synthesis of 5,6-dihydrovaltrate (2), the bioisostere of valtrate (1) showing anti-HIV activity by inhibition for nuclear export of Rev, has been achieved from the commercially available iridoid genipin (3). Analysis of steric influence of the substituents linked to the three hydroxyl groups was conducted by the synthesized three analogs (2a–2c). Consequently, attenuation of steric hindrance around the epoxy portion was revealed to enhance inhibitory potency for Rev-export. In addition to this finding, 1-acetoxy analog 2b was disclosed as the promising Rev-export inhibitor superior to 1.

The concise synthesis of 5,6-dihydrovaltrate, the Rev-export inhibitor, has been achieved from the commercially available iridoid genipin. By use of this synthetic protocol, 1-acetoxy analog 2b was disclosed as the enhanced Rev-export inhibitor.Figure optionsDownload as PowerPoint slide