69 エリスロノリドAの改良合成(口頭発表の部)

概要

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For recent years, we have been studying on the stereoselective total synthesis of naturally occuring products having complex chemical structures and improtant biological activities, such as macrolide and polyether antibiotics. Erythromycin A (1) is a well known macrolide antibiotic and we have already reported the total synthesis of (9S)-9-dihydroerythronolide A (3), however some problems, for example lactonization, remain unsolved. We would like to report here an improved synthetic approach to (2) starting from D-glucose. Construction of the chiral centers were carried out by the methods which were previously deveroped in our laboratory, and synthesis of the sulfone (9) and the aldehyde (16) were accomplished. Coupling of (9) and (16) (n-BuLi, Et_2O, -60℃) proceeded smoothly and after desulfonylation with sodium amalgam in Me0H-AcOEt at ?10℃, (18) was isolated in 63% yield. Remaining chiral centers at C_5 and C_6 were easily introduced by a base catalized epimerizatoin (K_2CO_3, MeOH, r.t.) and a non-chelation controlled alkylation of the ketone (MeLi, THF, -78℃). Thus obtained (22) was converted to the seco-acid (26). Cyclization of (26) by modified Corey's method in the presence of DMAP, which improved the yield remarkably, afforded the lactone (27) in 60% yield. Lactonization using other methods and transformation of (27) into (2) are now under investigation.
天然有機化合物討論会の論文
1988-09-26