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

  • Bioorg Med Chem. 2010 Aug 15;18(16):5975-80. doi: 10.1016/j.bmc.2010.06.079.
Satoru Tamura  1 ,  Katsuaki Fujiwara ,  Nobuhiro Shimizu ,  Shingo Todo ,  Nobutoshi Murakami
Affiliations
  • 1. Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
PMID: 20643553 DOI: 10.1016/j.bmc.2010.06.079
Abstract

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.