Facile Synthesis of Oleanolic Acid Monoglycosides and Diglycosides.docVIP

Molecules 2008, 13, 1472-1486; DOI: 10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /molecules Article Facile Synthesis of Oleanolic Acid Monoglycosides and Diglycosides Yu Sha, Mao-Cai Yan, Jiao Liu, Yang Liu and Mao-Sheng Cheng * Key Lab of New Drug Design and Discovery of Liaoning Province, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China; E-mails: syna2000@ (Y. S.); yanmaocai@126.com (M.-C. Y.); amityliu@163.com (Y. L.); ly_99@ (Y. L.) * Author to whom correspondence should be addressed: E-Mail: mscheng@263.net Received: 16 June 2008; in revised form: 18 July 2008 / Accepted: 18 July 2008 / Published: 22 July 2008 Abstract: Oleanolic acid and its glycosides are important natural products, possessing various attractive biological activities such as antitumor, antivirus and anti-inflammatory properties. In the present work, fifteen oleanolic acid saponins bearing various saccharide moieties, including 3-monoglycoside, 28-monoglycoside and 3,28-diglycoside, were easily synthesized in high yields. Benzyl was chosen as the protective group for the COOH(28) group, instead of commonly used methyl and allyl, to avoid difficulties in the final deprotection. Alkali-promoted condensation of the carboxylic acid with bromo- glycosides was found to be more efficient in the synthesis of 28-glycosides. Two approaches were investigated and proved practicable in the preparation of 3,28- diglycosides. This method is suitable for preparing oleanolic acid glycosides with structural diversity for extensive biological evaluation and structure-activity relationship study, and it also apply new idea for the corresponding synthetic methods to the glycoside derivatives of other triterpenoid. Keywords: Oleanolic acid, triterpenoid, glycoside, synthesis, glycosylation  Molecules 2008, 13 1473 Introduction Oleanolic aci