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.
Tamura
Satoru
S
Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
Fujiwara
Katsuaki
K
Shimizu
Nobuhiro
N
Todo
Shingo
S
Murakami
Nobutoshi
N
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D057889:Iridoid Glycosides / Q000138:chemical synthesis / Q000737:chemistry; D039823:Iridoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
D019380:Anti-HIV Agents; D057889:Iridoid Glycosides; D039823:Iridoids; D054321:rev Gene Products, Human Immunodeficiency Virus; C007834:genipin; C024750:didrovaltrate