Total Synthesis of (+)-Gracilamine Based on an Oxidative Phenolic Coupling Reaction and Determination of Its Absolute
Minami Odagi1, Yoshiharu Yamamoto1, Kazuo Nagasawa1
1Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, TUAT, 2-24-16, Naka-cho, Koganei city, 184-8588, Tokyo, Japan.
Abstract:
The enantioselective total synthesis of (+)-gracilamine (1) is described. The strategy features a diastereoselective phenolic coupling reaction followed by a regioselective intramolecular aza-Michael reaction to construct the ABCE ring system. The configuration at C3a in 1 was controlled by the stereocenter at C9a, which was selectively generated (91 % ee) by an organocatalytic enantioselective aza-Friedel-Crafts reaction developed by our research group. This synthesis revealed that the absolute configuration of (+)-gracilamine is 3aR, 4S, 5S, 6R, 7aS, 8R, 9aS.
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