Of ->physostigmine

Johnson has described a method for the estimation of physostigmine in the salicylate for the determination of minute amounts of the alkaloid Ellis, Plaehte and Straus have devised processes depending on (a) inhibition of serum choline-esterase by the alkaloid, or (b) measurement of the colour intensity produced by the conversion of physostigmine to rubreserine in an alkaline medium. i ... 

XXXVIII), m.p. 128°, identical with the product obtained from physostigmine (XXXIX), and, as the latter had already been synthesised from 1-eseroline by Polonovski and Nitzberg,i the work of the American authors constituted the first complete synthesis of physostigmine. 

Physovenine, Cl4Hig03N2, was obtained by Salway from the mother liquors left after the separation of eseramine. It crystallises from a mixture of benzene and light petroleum in small, colourless prisms, m.p. 123°. Its salts are dissociated by water. With barium hydroxide physovenine liberates carbon dioxide and assumes a deep red colour, and, owing to the similarity of this behaviour with that of physostigmine, Salway suggested that physovenine may be an intermediate product in the formation of eseroline from physostigmine. 

Ellis, Krayer and Plachte have shown that the degradation products of physostigmine, eseroline and eserine-brown do not inhibit choline-esterase, but rubreserine and eserine-blue are inhibitors in vitro, having... 

A further development of this subject is due to Aeschlimann and Reinert, who found that in the series represented by (XLI) thedimethyl-carbamic ester (XLI R = Me) and the methylphenylcarbamic ester (XLI R = Ph) were at least as active as physostigmine in stimulating peristalsis. The miotic activity of the dimethylcarbamic ester (prostig-mine, neostigmine) is similar to that of physostigmine, that of the methylphenylcarbamic ester being weak. 

Physostigmine, an alkaloid obtained from a West African plant, is used in the treatment of glaucoma. Treatment of physostigmine with methyl iodide gives a quaternary ammonium salt. What is the structure of this salt ... 

The relative inaccessibility of physostigmine led to molecular dissection studies to define the parts of the molecule necessary for activity. A surprisingly simple derivative of m-hydroxy-aniline, neostigmine (40), proved to have the same activity as the complex heterocyclic molecule. In addition, this drug has found use as a cholinsterase inhibitor in pathologic conditions such as myasthenia gravis, marked by insufficient muscle tone. Reaction of m-dimethylaminophenol (37) witn pnosgene affords tne... 

Boyer EW, Quang L, Woolf A, et al Use of physostigmine in the management of gamma-hydroxybutyrate overdose (letter). Ann Emerg Med 38 346, 2001 Buffiim J, Moser C MDMA and human sexual dysfunction. J Psychoactive Drugs 18 355-359, 1986... 

The limited effectiveness of physostigmine did, however, encourage the development of longer-acting orally effective anticholinesterases such as tacrine (tetrahydroamino-acrydine), velnacrine and donepezil. 

Figure 4.57 Synthesis map showing starting materials used for the synthesis of physostigmine.

Figure 4.58 Synthesis tree for synthesis of physostigmine by the Yu method.

Julian, P.L., PM, J., Boggess, D. (1934) Studies in the Indole Series. II. The Alkylation of 1-Methyl-3-formyloxindole and a Synthesis ofthe Basic Ring Structure of Physostigmine. Journal of the American Chemical Society, 56, 1797-1801. 

Trost, B.M. Zhang, Y. (2006) Molybdenum-Catalyzed Asymmetric AUylation of 3-Alkyloxindoles Application to the Formal Total Synthesis of (—)-Physostigmine. Journal of the American Chemical Society, 128,4590M591. 

Mukai, C., Yoshida, T., Sorimachi, M., Odani, A. (2006) Co2(CO)8-Catalyzed Intramolecular Hetero-Pauson-Khand Reaction of Alkynecarbodiimide Synthesis of ( )-Physostigmine. Organic Letters, 8, 83-86. 

A total synthesis of (-)-physostigmine is accomplished from a chiral nitroolefin of Eq. 4.101 (Scheme 4.17).128... 

Node and Fuji have developed a new chiral synthesis of various alkaloids using chiral nitroalkene, (S)-(-)-2-methyl-2-(2 -nitrovinyl)-S-valerolactone. Scheme 8.11 shows a total synthesis of (-)-physostigmine, a principal alkaloid of the Calabar bean.53 The key nitroalkene is prepared by asymmetric nitroolefination of a-methyl-8-lactone using a chiral enamine (see... 

Ebert U, Oertel R, Wesnes K and Kirch W (1998). Effects of physostigmine on scopolamine-induced changes in quantitative electroencephalogram and cognitive performance. Human Psychopharmacology - Clinical and Experimental, 13, 199-210. 

Kim Y-B, Cheon K-C, Hur G-H, Phi T-S, Choi S-J, Hong D, Kang J-G. Effects of combinational prophylactics composed of physostigmine and procyclidine on soman-induced lethality, seizures and brain injuries. Environ. Toxicol. Pharmacol. 11(1) 15-21,2002. 

Philippens IHCHM, Melchers BPC, Wolthuis OL. Active avoidance in guinea pigs, effects of physostigmine and scopolamine. Pharmacol. Biochem. Behav. 42 285-289, 1992. 

Philippens IHCHM, Olivier B, Melchers BPC. Effects of physostigmine on the startle in guinea pigs two mechanisms involved. Pharmacol. Biochem. Behav. 58 909-913, 1997. 

Philippens IHCHM, Melchers BPC, Olivier B, Bruijnzeel PLB. Scopolamine augments the efficacy of physostigmine against soman poisoning in guinea pigs. Pharmacol. Biochem Behav. 65 175-182, 2000b. 

Philippens IHCHM, Groen B, Vanwersch RAP. Direct effects of physostigmine as a pretreatment in guinea pigs side effects and efficacy against soman. Proc.TG004 meeting, Medicine Hat, Canada, 2003. 

Van den Beukel I, van Kleef RGDM, Oortgiesen M. Differential effects of physostigmine and organophosphates on nicotinic receptors in neuronal cells of different species. NeuroToxicol. 19(6) 777-788, 1998. 

Liijequist R, Mattiia MJ. (1979). Effect of physostigmine and scopoiamine on the memory functions of chess piayers. Med Biol. 57(6) 402-5. 

Degroot A, Parent M. 2001. Infusions of physostigmine into the hippocampus or the entorhinal cortex attenuate avoidance retention deficits produced by intra-septal infusions of the GABA agonist muscimol. Brain Research 920(1-2) 10-18. 

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