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

Satoru Tamura; Katsuaki Fujiwara; Nobuhiro Shimizu; Shingo Todo; Nobutoshi Murakami

doi:10.1016/j.bmc.2010.06.079

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

Satoru Tamura, Katsuaki Fujiwara, Nobuhiro Shimizu, Shingo Todo, Nobutoshi Murakami

SCI - Chemistry

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

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.

Original language	English
Pages (from-to)	5975-5980
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry
Volume	18
Issue number	16
DOIs	https://doi.org/10.1016/j.bmc.2010.06.079
Publication status	Published - 2010 Aug 15

Keywords

5,6-Dihydrovaltrate
Anti-HIV
Genipin
Iridoid
Rev-export inhibitor

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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

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.",

keywords = "5,6-Dihydrovaltrate, Anti-HIV, Genipin, Iridoid, Rev-export inhibitor",

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AU - Shimizu, Nobuhiro

AU - Todo, Shingo

AU - Murakami, Nobutoshi

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