Syntheses of dihydroartemisinic acid and dihydro-epi-deoxyarteannuin B incorporating a stable isotope label at the 15-position for studies into the biosynthesis of artemisinin

Abstract

[15-13C2H3]-Dihydroartemisinic acid (3a) and [15-13CH3]-dihydro-epi-deoxyarteannuin B (7b), intended for evaluation in vivo as biosynthetic precursors to artemisinin, have been obtained from a reconstructive synthesis. The decalenone acid 8 from acid degradation of artemisinin (1) serves as a common intermediate: following addition of labeled methyl Grignard reagent to 8, either labeled precursor can be prepared in good yield by varying the work-up conditions employed. It is shown that both compounds are prone to autoxidation on storage and that the products of such oxidation and subsequent rearrangement reactions might be confused with bona fide metabolites when using these labeled precursors in feeding experiments designed to determine the biosynthetic route to artemisinin in Artemisia annua. © 2001 Elsevier Science Ltd. All rights reserved.