functionalisation of artemisinin and its ring-contracted derivativesfunctionalisation青蒿素及其ring-contracted衍生品.pdfVIP

Molecules 2007, 12, 395-405 molecules ISSN 1420-3049 Full Paper Functionalisation of Artemisinin and Its Ring-contracted Derivatives Tine Van Neck, Sarah Van Mierloo and Wim Dehaen* Department of Chemistry, University of Leuven, Celestijnenlaan 200F B-3001 Leuven, Belgium * Author to whom correspondence should be addressed; E-mail: wim.dehaen@chem.kuleuven.be; Tel. (+32) 16 32 74 39; Fax (+32) 16 32 79 90 Received: 1 March 2007; in revised form: 8 March 2007 / Accepted: 8 March 2007 / Published: 9 March 2007 Abstract: Isoxazoline analogues of artemisinin were obtained in low yield and low diastereoselectivity from the 1,3-dipolar cycloaddition of nitrile oxides. Alternatively, starting from the aldehyde 7, a number of transformations - Wittig reaction and reduction, Henry reaction and cyanohydrin formation - were achieved in significantly higher yields. In the cases where a new stereocenter was introduced this occured diastereoselectively. Keywords: Artemisinin, ring contraction, aldehyde, 1,3-dipolar cycloaddition, nitrile oxide. Introduction Artemisinin (1, qinghaosu, arteannuin) is a potent antimalarial agent with an interesting trioxane sesquiterpene structure, and has been isolated from the plant Artemisia annua . This plant has been used in Traditional Chinese Medicine for nearly 2000 years as a cure for malaria. Great efforts have been focused on chemical modifications of the artemisinin structure in order to improve the biological activity. Semis