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

详细信息    查看全文

• 作者：Satoru Tamura ; Katsuaki Fujiwara ; Nobuhiro Shimizu ; Shingo Todo ; Nobutoshi Murakami
• 关键词：Rev-export inhibitor ; Anti-HIV ; 5 ; 6-Dihydrovaltrate ; Iridoid ; Genipin
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2010
• 出版时间：15 August 2010
• 年：2010
• 卷：18
• 期：16
• 页码：5975-5980
• 全文大小：246 K

文摘

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.