Synthesis of cynaropicrin-d(4)

Takuya Sato; Shihori Hara; Makiko Sato; Keita Ogawa; Michael Adams; Toyonobu Usuki

doi:10.1016/j.bmcl.2015.10.065

Synthesis of cynaropicrin-d(4)

Bioorg Med Chem Lett. 2015 Dec 1;25(23):5504-7. doi: 10.1016/j.bmcl.2015.10.065. Epub 2015 Oct 23.

Authors

Takuya Sato¹, Shihori Hara¹, Makiko Sato¹, Keita Ogawa¹, Michael Adams², Toyonobu Usuki³

Affiliations

¹ Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University, 7-1 Kioicho, Chiyoda-ku, Tokyo 102-8554, Japan.
² Bacoba AG, Einsiedlerstrasse 25, CH-8820 Wädenswil, Switzerland.
³ Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University, 7-1 Kioicho, Chiyoda-ku, Tokyo 102-8554, Japan. Electronic address: t-usuki@sophia.ac.jp.

PMID: 26520660
DOI: 10.1016/j.bmcl.2015.10.065

Abstract

Cynaropicrin is a guaianolide sesquiterpene lactone, which has potent in vitro and in vivo inhibitory activity against Trypanosoma brucei, the protozoan parasite that causes human African trypanosomiasis (HAT; sleeping sickness). Herein, we describe the synthesis of cynaropicrin's deuterated derivative, cynaropicrin-d4, by the replacement of the side chain of natural cynaropicrin. The synthesized cynaropicrin-d4 could be employed as an internal standard for liquid chromatography-mass spectrometry (LC-MS) analysis, in the pharmacokinetic study of cynaropicrin. This could potentially advance the study of this therapeutic lead.

Keywords: Cynaropicrin; Deuterium; Guaianolide; Pharmacokinetic study; Trypanosoma brucei.

MeSH terms

Deuterium / chemistry*
Lactones / chemical synthesis*
Lactones / chemistry
Molecular Structure
Sesquiterpenes / chemical synthesis*
Sesquiterpenes / chemistry
Trypanocidal Agents / chemical synthesis
Trypanocidal Agents / chemistry

Substances

Lactones
Sesquiterpenes
Trypanocidal Agents
cynaropicrin-d
Deuterium
cynaropicrin