synthetic studies on erythromycin derivatives reactivity of the c12-21 alkene红霉素衍生物合成研究c12-21烯烃的反应性.pdf

Molecules 2006, 11, 121-129 molecules ISSN 1420-3049 Synthetic Studies on Erythromycin Derivatives: Reactivity of the C12-21 Alkene Wei-Min Chen Department of Medicinal Chemistry, School of Pharmacy, Jinan University, Guangzhou, 510632, P.R. China; E-mail: twmchen@ Received: 8 January 2006 / Accepted: 23 January 2006 / Published: 31 January 2006 Abstract: The reactivity of the C12-21 alkene of some erythromycin A derivatives was studied. This double bond was easily oxidized to the corresponding epoxide with excellent stereoselectivity. A single crystal X-ray structure showed that the epoxide moiety was on the same side as the acetonide. When an erythromycin derivative containing a C12-21 alkene was treated with diazomethane a [3+2] cycloaddition affording a pyrazoline occurred. In the case of 6-O-allylated erythromycin derivatives the C12-21 alkene was selectively epoxidized in the presence of the 6-O-allyl moiety. These results show that the C12-21 alkene is an active reaction site, which can be used for useful further modification of erythromycin derivatives. Keywords: Erythromycin, alkene, epoxidation, cycloaddition, pyrazoline. Introduction Erythromycin A (1, Figure 1) is one of the most successful antibiotics ever discovered, and has been used for the treatment of bacterial infections over the past 50 years. Despite its popularity, however, erythromycin suffers from several problems associated with its use. First, erythr