Enantioselective total synthesis of quadrigemine C and psycholeine.
The first total syntheses of higher-order members of the polypyrrolidinoindoline alkaloid family are reported. The synthesis of quadrigemine C (1) and psycholeine (3) begins with synthetic meso-chimonanthine (4), which is synthesized from commercially available oxindole and isatin in 13 steps and 35% overall yield. Double Stille cross coupling of diiodide 7, available in three steps from 4, with vinylstannane 8 produces dibutenanilide 9. Double catalytic asymmetric Heck cyclization of 9 simultaneously installs the two peripheral quaternary stereocenters and desymmetrizes this advanced meso precursor to deliver the chiral, decacyclic intermediate 11 in 62% yield and 90% ee. In two additional steps, 11 is converted to 1, which upon treatment with acid generates 3. The synthesis of quadrigemine C (1), which rigorously confirms its relative and absolute configuration, was executed in 19 linear steps (2% overall yield) from commercially available starting materials.
Lebsack
Alec D
AD
Department of Chemistry, 516 Rowland Hall, University of California Irvine, California 92697-2025, USA.
Link
J T
JT
Overman
Larry E
LE
Stearns
Brian A
BA
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D009510:New Caledonia; D010946:Plants, Medicinal / Q000737:chemistry*; D013237:Stereoisomerism
D000470:Alkaloids; D007202:Indicators and Reagents; D007211:Indoles; C077371:psycholeine; C051765:quadrigemine A