Efficient formal total synthesis of physostigmine and physovenine: conformational analysis of key intermediates.
An efficient route for the formal total synthesis of physostigmine (1) and physovenine (2), alkaloids from 5-methoxyindole-3-acetonitrile, through a Grignard reagent 1,4-addition, is described. 2-Hydroxyindolenine 5, the key advanced intermediate for the synthetic targets, was converted either to esermethole (12) via a high-yielding (28%) seven-step sequence or to the C-ring oxygenated analogue 15 in a five-step sequence and 23% overall yield. (1)H NMR and molecular modeling analyses of esermethole (12) and the furoindolines 13 and 15 were used to deconvolute weighted time-average vicinal coupling constants to provide definite solution-state conformational preferences in CD(2)Cl(2) solvent.
Morales-Ríos
Martha S
MS
Departamento de Química, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado 14-740, México, DF, 07000 México.
Santos-Sánchez
Norma F
NF
Joseph-Nathan
Pedro
P
D007887:Fabaceae / Q000737:chemistry; D026121:Indole Alkaloids / Q000737:chemistry / Q000302:isolation & purification*; D008956:Models, Chemical; D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular; D029906:Physostigma / Q000737:chemistry*; D010830:Physostigmine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry
D026121:Indole Alkaloids; C092643:physovenine; D010830:Physostigmine