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Updated: Jun 10, 2026
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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Concise synthesis of 5,6-dihydrovaltrate leading to enhanced Rev-export inhibitory congener
Satoru Tamura1, Katsuaki Fujiwara, Nobuhiro Shimizu
1Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
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.
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