Studies toward the Synthesis of Lepadiformine A.
Herein is described an original approach to access a tricyclic framework of the lepadiformine-type alkaloids. A Grignard/N-acylpyridinium salt reaction of a 4-methoxytetrahydroquinoline is the key carbon-carbon bond-forming step that was used to establish the desired absolute stereochemistry at the C2 position of the target alkaloid. The synthesis features an allylation reaction with an N-acyliminium ion to set the C10 quaternary stereocenter, a mild dissolving-metal cleavage of hindered phenyl carbamates, and an aminoiodocyclization to form the pyrrolidine ring. While this route does not provide the correct C10 stereochemistry, it showcases an efficient method to build analogues with the ring system of this class of alkaloids in 11 steps overall.
Department of Chemistry, North Carolina State University , Raleigh, North Carolina 27695-8204, United States.
Sergey V
SV
Tsukanov
Department of Chemistry, North Carolina State University , Raleigh, North Carolina 27695-8204, United States.
Lucas R
LR
Marks
Department of Chemistry, North Carolina State University , Raleigh, North Carolina 27695-8204, United States.
Daniel L
DL
Comins
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D000818:Animals; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D003500:Cyclization; D015394:Molecular Structure; D066244:Proton Magnetic Resonance Spectroscopy; D013237:Stereoisomerism; D014561:Urochordata / Q000737:chemistry
D000470:Alkaloids; C431548:lepadiformine