Toward resolving the resveratrol conundrum : synthesis and in vivo pharmacokinetic evaluation of BCP-resveratrol

Toward resolving the resveratrol conundrum : synthesis and in vivo pharmacokinetic evaluation of BCP-resveratrol

ACS Medicinal Chemistry Letters

10.1021/acsmedchemlett.7b00018

https://doi.org/10.1021/acsmedchemlett.7b00018

Yi Ling Goh, Yan Ting Cui, Vishal Pendharkar, Vikrant A. Adsool

24 April 2017

Goh, Y. L.; Cui, Y. T.; Pendharkar, V.; Adsool, V. A., Toward resolving the resveratrol conundrum : synthesis and in vivo pharmacokinetic evaluation of BCP-resveratrol. ACS Medicinal Chemistry Letters 2017, 8 (5), 516-520.

Over the last few decades, resveratrol has gained significance due to its impressive array of biological activities; however, its true potential as a drug has been severely constrained by its poor bioavailability. Indeed, several studies have implicated this bioavailability trait as a major road-block to resveratrol’s potential clinical applications. To mitigate this pharmacokinetic issue, we envisioned a tactical bioisosteric modification of resveratrol to bicyclo[1.1.1]pentane (BCP) resveratrol. Relying on the beneficial bioisosteric potential demonstrated by the BCP-scaffold, we hypothesized that BCP–resveratrol would have an inherently better in vivo PK profile as compared to its natural counterpart. To validate such a hypothesis, it was necessary to secure a synthetic access to this novel structure. Herein we describe the first synthesis of BCP–resveratrol and disclose its PK properties.

PublisherCopyrights

This work was performed in collaboration with GSK, Singapore.

https://oar.a-star.edu.sg/communities-collections/articles/13954

1948-5875

Institute of Chemical and Engineering Sciences