Biomimetic total synthesis of (+/-)-8-oxoerymelanthine.
Erymelanthine 1 and 8-oxoerymelanthine 2 are unique erythrina alkaloids containing a pyridine ring. We synthesized (+/-)-8-oxoerymelanthine 2 in 2.0% overall yield using the following key reactions. The characteristic 6-5-6-6-membered ring system was constructed by the stereoselective intermolecular Diels-Alder reaction. Oxidative cleavage of the aromatic D-ring was conducted chemo- and regioselectively by ozonolysis in the presence of BF(3)-etherate. This cleavage site is identical to the site cleaved during the biosynthesis of erymelanthine 1. Nitrogen incorporation was achieved by aminolysis. Conversion of the D-ring pyridone to the corresponding pyridine was efficiently accomplished by palladium-catalyzed reduction of aryl triflate 21. This is not only the first total synthesis of (+/-)-8-oxoerymelanthine 2 (where the D-ring is pyridine) but also, more importantly, a biomimetic total synthesis of an erythrinan D-aza alkaloid.
Yoshida
Yuki
Y
Laboratory of Drug Design and Medicinal Chemistry, Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo 194-8543, Japan.
Mohri
Kunihiko
K
Isobe
Kimiaki
K
Itoh
Toshimasa
T
Yamamoto
Keiko
K
D000470:Alkaloids / Q000096:biosynthesis / Q000138:chemical synthesis* / Q000737:chemistry*; D001372:Aza Compounds / Q000737:chemistry; D032701:Biomimetics; D004895:Erythrina / Q000737:chemistry / Q000378:metabolism; D009584:Nitrogen / Q000737:chemistry; D010084:Oxidation-Reduction; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry*
C552318:8-oxoerymelanthine; D000470:Alkaloids; D001372:Aza Compounds; D011725:Pyridines; C549160:erymelanthine; D009584:Nitrogen