Total synthesis of (.+-.)-14-epicorynoline, (.+-.)-corynoline, and (.+-.)-6-oxocorynoline

Efficient Synthesis of (−)‐Corynoline by Enantioselective Palladium‐Catalyzed α‐Arylation with Sterically Hindered Substrates

“…Corynoline,isolated from corydalisincisa,isanacetylcholinesterase inhibitor that exhibits diverse pharmacological effects,i ncluding inhibition of cell adhesion, [17a] fungal and cytotoxicity. [17] Despite an umber of synthetic efforts, [6] an efficient enantioselective synthesis remains highly desirable. Considering the synthetic challenge posed by the tetracyclic skeleton bearing three contiguous chiral centers and one allcarbon quaternary center,wedesigned afive-step asymmetric synthesis of (À)-corynoline by applying the enantioselective palladium-catalyzed a-arylation of sterically hindered substrates (Scheme 2).…”

“…The search for asymmetric catalytic methods for the efficient construction of all-carbon quaternary centers continues to be amajor interest in organic synthesis.Inparticular, asymmetric catalytic methods applicable to the synthesis of chiral natural products and therapeutic agents containing all-carbon quaternary centers remain in high demand. [1,2] Chiral 2-alkyl-2aryl-1,2,3,4-tetrahydronaphthalene and quinoline motifs are found in many biologically important natural products and drugs,s uch as the antidepressant (S)-nafenodone (1), [3] the Sceletium alkaloids (+ +)-sceletium A-4 (2) [4] and (+ +)-tortuosamine (3), [5] as well as the acetylcholinesterase inhibitors (+ +)-corynoline (ent-4), [6] (+ +)-DeN-corynoline (ent-5), [7] and corynoloxine (6; Figure 1). [8] Although there has been agreat deal of synthetic effort, efficient asymmetric syntheses,i n particular those based on asymmetric catalytic methods,a re still lacking.…”

New One-Pot Methodologies for the Modification or Synthesis of Alkaloid Scaffolds

“…A mechanistic study was not published until 1983 when Cushman studied the electronic and steric effects on the stereochemical outcome [35]. A low yield was obtained when phenyl substituted succinic anhydride was used instead of succinic anhydride (Scheme 16, Equation 2).…”

Alkaloids

“…Corynoline was synthesized by two different methods: the photocyclization of enamides [237] and the condensation of a piperonylidenemethylamine with a substituted homophthalic anhydride [238]. …”