First Atroposelective Total Synthesis of Enantiomerically Pure Ancistrocladidine and Ancistrotectorine.
The first regio- and stereoselective total synthesis of the axially chiral 7,3'-coupled naphthylisoquinoline alkaloids ancistrocladidine (1) and ancistrotectorine (2) has been described. Both possess a 7,3'-coupled axis, which before now, was difficult to attain synthetically. Moreover, target 2 has a sensitive relative cis-array of the two methyl groups at C1 and C3 in the tetrahydroisoquinoline part. The key step in the chosen strategy was the construction of the biaryl axis in accordance with the "lactone method": the two molecular halves, which were activated in an "inverse-halogenated" form, were prefixed by an ester bridge, followed by intramolecular coupling, and atroposelective cleavage of the lactone auxiliary bridge delivered the desired biaryl scaffold.
Institut für Organische Chemie, Universität Würzburg, Am Hubland, 97074, Würzburg, Germany. bringman@chemie.uni-wuerzburg.de.
Gerhard
G
Bringmann
Institut für Organische Chemie, Universität Würzburg, Am Hubland, 97074, Würzburg, Germany.
Narasimhulu
N
Manchala
Institut für Organische Chemie, Universität Würzburg, Am Hubland, 97074, Würzburg, Germany.
Tobias
T
Büttner
Institut für Organische Chemie, Universität Würzburg, Am Hubland, 97074, Würzburg, Germany.
Barbara
B
Hertlein-Amslinger
Institut für Organische Chemie, Universität Würzburg, Am Hubland, 97074, Würzburg, Germany.
Raina
R
Seupel
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D009284:Naphthols / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000470:Alkaloids; D007546:Isoquinolines; D007783:Lactones; D009284:Naphthols; C451486:ancistrocladidine
alkaloids; biaryls; cross-coupling; lactones; total synthesis