Eserine synthesis

A.6 Quinine, quinidine, and cinchonine synthesis pathway 123 2.2.4.7 Eserine synthesis pathway 124... 

Julian, P.L. PM, J. (1935) Studies in the Indole Series. V. The Complete Synthesis of Physostigmine (Eserine). Journal of the American Chemical Society, 57, 755-757. 

Wunberg, J.B.P.A. Speckamp, W.N. (1978) New Total Synthesis of dl-Physostigmine (dl-Eserine) Via Regioselective NaBH4-reduction of Imides. Tetrahedron, 34, 2399-2404. 

Eserine (physostigmine) has a pyrroloindole skeleton. This alkaloid is used as an anticholinesterase drug, which is fairly important in the treatment of Alzheimer s disease. Eserine is synthesized in Physostigma venenosum and stored in the seeds of this leguminous plant. The synthesis pathway starts with tryptamine, which is transformed into eserine (Eigure 45). 

Once the medicinal properties of I and II were appreciated, the inevitable synthesis of carbamate analogs followed. The anticholinesterase activity of physostigmine- and eserine-related synthetics suggested their possible use as Insecticides but tests of early compounds failed, due to the quaternary ammonium barrier to penetration of the insect cuticle present in them. 

A new synthesis " of the eserine ring system (11) (Scheme 3) proceeds via a nitrophenylsuccinimide derivative, and is unique among existing syntheses in that ring B, and not ring c, is closed in the final stage. 

The main poisonous substance of Calabar beans was isolated in 1864, and was named physostigmine [IJ.The plane structure of this alkaloid was determined in 1925, and the absolute stereochemistry of (—)-physostigmine was clarified by degradation studies in 1969 [2,3]. Subsequently, the total synthesis of DL-physostigmine was achieved [4]. Calabar beans were known as Esere by the indigenous people, and so physostigmine is also known as eserine. 

Dihydroindoles.—new synthesis of 2,2-disubstituted dihydroindoles from enamines and aryl azides has been reported. The reaction is envisioned as proceeding via an unstable triazoline which collapses with loss of nitrogen to give the dihydroindole or an amidine (Scheme 100). A number of eserine derivatives have been prepared by a simple three-stage process (Scheme 101). ... 

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