ABSTRACT
Cynaropicrin is found in artichoke (Cynara scolymus) and is the source of its bitter taste and it is a sesquiterpene lactone with a 5-7-5 tricyclic skeleton, six chiral centers, and four exo-olefins. This natural product has numerous attractive biological activities including the inhibition of NF-κB activation, antihepatitis C activity, and antitrypanosomal activity. In this study, the first total synthesis of cynaropicrin was achieved starting from (S)-α-pinene. The synthesis involved a stereoselective Favorskii rearrangement and an indium-promoted diastereoselective Barbier reaction.
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.
Subject(s)
Deuterium/chemistry , Lactones/chemical synthesis , Sesquiterpenes/chemical synthesis , Lactones/chemistry , Molecular Structure , Sesquiterpenes/chemistry , Trypanocidal Agents/chemical synthesis , Trypanocidal Agents/chemistryABSTRACT
Cynaropicrin is a guaianolide sesquiterpene lactone with a 5-7-5 tricyclic skeleton, four exo-olefins, and two hydroxyl groups. Recently, it was found that the compound is a potent in vitro and in vivo inhibitor of the protozoan parasite Trypanosoma brucei, which causes human African trypanosomiasis (HAT; sleeping sickness). In this Letter, chemical derivatization of cynaropicrin and the structure-activity-relationship (SAR) study against T. brucei is described.
