116103-15-2

Upstream product

• 150333-84-9 (-)-(3S)-1,3-dimethyl-5-methoxy-3-acetic acid benzylamide 
• 129011-67-2 methyl 2,3-dihydro-5-methoxy-1,3-dimethyl-2-oxo-1H-indole-3-acetate 
• 139115-79-0 2-(5-methoxy-1,3-dimethyl-2-oxoindolin-3-yl)acetic acid 
• 150407-40-2 2-(5-methoxy-1,3-dimethyl-2-oxoindolin-3-yl)acetic acid 
• 107485-89-2 (3aS,8aS)-5-Methoxy-3a,8-dimethyl-3,3a,8,8a-tetrahydro-2H-pyrrolo[2,3-b]indole-1-carboxylic acid ((S)-1-phenyl-ethyl)-amide 
• 57-47-6 Physostigmin 
• 100-46-9 benzylamine 
• 74-88-4 methyl iodide 
• 469-22-7 eseroline 
• 100-39-0 benzyl bromide 
• 104069-11-6 (3aS,8aR)-5-methoxy-3a,8-dimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole 

Downstream Products

• 116103-16-3 (-)-(3aS)-1-benzyl-3a,8-dimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-ol 
• 219920-81-7 (-)-N¹,N⁸-bisnorcymserine 
• 145209-43-4 N¹-benzylnorphenserine 
• 290294-27-8 1-benzyl-3a-methyl-2,3,3a,8a-tetrahydro-1H-pyrrolo[2,3-b]indol-5-one 
• 290294-26-7 1-benzyl-5-methoxy-3a-methyl-2,3,3a,8a-tetrahydro-1H-pyrrolo[2,3-b]indole-8-carbaldehyde 
• 438245-98-8 C₁₉H₂₂N₂O 
• 116103-17-4 N¹-benzylnorphysostigmine 
• 6091-57-2 (-)-eseramine 
• 220697-91-6 (-)-(3aS)-1-benzyl-3a,8-dimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl-N-4'-benzyloxyphenylcarbamate 

Relevant academic research and scientific papers

Compound useful in the treatment or prevention of cognitive disorders associated with diabetes and associated methods

Described is the efficient synthesis of an easy to manipulate and utilize, soluble tartrate salt of a potent, reversible butyrylcholinesterase inhibitor, (?)-(3aS)-3a-methyl-1,2,3,3a,8,8a-hexahydropyrrolo-[2,3-b]indol-5-yl N—4′-isopropylphenylcarbamate (“

Racemic N1-norphenserine and its enantiomers: Unpredicted inhibition of human acetyl- and butyrylcholinesterase and β-amyloid precursor protein in vitro

The optically pure enantiomers of N1-norphenserine (15, 16) were synthesized and its racemate 17 was prepared by mixing equal parts of each enantiomer. (-)-N1-Norphenserine (15) was prepared by partial synthesis initiated from the natural product, (-)-physostigmine (1). (+)-N 1-Norphenserine (16) was prepared by total synthesis using the Julian oxindole route, with modifications. The in vitro inhibitory activities of 15-17 were quantified against human erythrocyte AChE and plasma BChE as well as against human neuroblastoma cell β-amyloid precursor protein secretion in cell culture. All were active. Racemic compound (17) with a high AChE and β-amyloid precursor protein inhibitory action may warrant further assessment in Alzheimer's disease models.

A practical conversion of natural physostigmine into the potent butyrylcholinesterase inhibitor N1,N8-bisnorcymserine

A rapid novel synthetic route to the potent reversible butyrylcholinesterase inhibitor (-)-N1,N8-bisnorcymserine (1) is reported from physostigmine (2) in a 20% total yield. Details on the formation of the imino-quinone 6 obtained in the oxidation of N1-benzylnoresermethole (4) and its conversion into N1-bisnoreseroline (7) are given. As expected, the product of this synthesis, (1), had identical biological activity to the same agent produced by total synthesis. (C) 2000 Elsevier Science Ltd.

4'-Hydroxyphenylcarbamates of (3aS)eseroline and (3aS)-N(1)- noreseroline: Potential metabolites of the Alzheimer's anticholinesterase drug phenserine

4'-Hydroxyphenylcarbamates of (3aS)-eseroline (3) and (3aS)-N(1)- noreseroline (4), as predicted metabolites of phenserine (1), were synthesized. Biological evaluation showed that 3 and 4 possessed potent activities for inhibition of acetylcholinesterase and butyrylcholinesterase in vitro. In contrast the intermediates, 4'-benzyloxyphenserine (8) and 4'- benzyloxy N(1)-benzylphenserine (12), demonstrated unusually potent and selective activities against butyrylcholinesterase.

PROGRESS TOWARDS A PRACTICAL TOTAL SYNTHESIS OF CALABAR ALKALOIDS: TOTAL SYNTHESIS OF (-)-ESERMETHOLE AND (-)-PHYSOVENOL METHYL ETHER FROM (3S)-1,3-DIMETHYL-3-CARBOXYMETHYL-5-METHOXYOXINDOLE

Chemical resolution of the oxindoleacetic acid (7) with brucine in water yielded the acid (7a) of (3S)-absolute configuration.Acid (7a), in using conventional methods, was converted into nitrile (8a), lactone (9a) and amides (10a), and (11a) respectively.Amide (10a), on reduction with LAH in refluxing THF, directly yielded (-)-esermethole (12a), and amide (11a) similarly gave (-)-N1-benzylnoresermethole (13a).Reduction of ester (6a) with LAH in refluxing THF yielded (-)-physovenol methyl ether (14a).

Synthesis and Anticholinesterase Activity of (-)-N1-Norphysostigmine, (-)-Eseramine, and Other N(1)-Substituted Analogues of (-)-Physostigmine

(-)-N1-Benzylnorphysostigmine (4), prepared from synthetic (-)-O-methyl-N1-noreseroline (1) by N-benzylation, ether cleavage, and reaction of (-)-N1-benzylnoreseroline (3) with methyl isocyanate, was the intermediate used to prepare the title compounds.Catalytic debenzylation of (4) afforded (-)-N1-norphysostigmine (5), and (-)-eseramine (6) was obtained by reaction of 5 with methyl isocyanate.Reductive N-methylation of 5 gave (-)-physostigmine (9) while reaction of 5 with allyl bromide and phenethyl bromide afforded carbamates 7 and 8, respectively.Data on the in vitro potencies (IC50) and activities of certain of these compounds (4-8) as inhibitors of electric eel acetyl cholinesterase are reported. (-)-N1-Norphysostigmine (5) was found to be similarly potent against AChE as (-)-physostigmine (9).