469-22-7

Basic information

• Product Name: eseroline
• Synonyms: eseroline;(3aS)-1,2,3,3a,8,8a-Hexahydro-1,3aα,8α-trimethylpyrrolo[2,3-b]indol-5-ol;(3aS,8aR)-1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-ol
• CAS NO: 469-22-7
• Molecular Formula: C₁₃H₁₈N₂O
• Molecular Weight: 218.29
• Mol File: 469-22-7.mol

Chemical Properties

• Boiling Point: 366.3°Cat760mmHg
• Flash Point: 189.6°C
• Appearance: /
• Density: 1.16g/cm³
• Vapor Pressure: 6.99E-06mmHg at 25°C
• Refractive Index: 1.597
• CAS DataBase Reference: eseroline(CAS DataBase Reference)
• NIST Chemistry Reference: eseroline(469-22-7)
• EPA Substance Registry System: eseroline(469-22-7)

Safety Data

• Hazardous Substances Data: 469-22-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Eseroline is used as an analgesic agent for its potent pain-relieving effects, which are mediated through the μ-opioid receptor. This makes it a valuable component in the development of pain management medications.
Used in Metabolism Research:
As a metabolite of physostigmine, eseroline is used in research to study the metabolic pathways and interactions involving acetylcholinesterase inhibitors and opioid agonists. This can contribute to a better understanding of the mechanisms of action and potential therapeutic applications of these types of drugs.

InChI:InChI=1/C13H18N2O/c1-13-6-7-14(2)12(13)15(3)11-5-4-9(16)8-10(11)13/h4-5,8,12,16H,6-7H2,1-3H3/t12-,13+/m1/s1

Upstream product

• 104069-12-7 (3aR,8aS)-5-methoxy-1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole 
• 29347-10-2 physostigmine 
• 57-47-6 Physostigmin 
• 469-23-8 (3AS-cis)-5-ethoxy-1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethyl-pyrrolo[2,3-b]indole 
• 4747-68-6 cycloheptyl isocyanate 
• 2909-38-8 m-chlorophenyl isocyanate 
• 104069-11-6 (3aS,8aR)-5-methoxy-3a,8-dimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole 
• 131101-13-8 (5-methoxy-1,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-3-yl)acetonitrile 
• 1094042-30-4 (S)-3-iodomethyl-5-methoxy-1,3-dimethylindolin-2-one 
• 104-12-1 p-chlorphenylisocyanate 
• 4411-25-0 1-adamantyl isocyanate 
• 136569-53-4 N-[2-((S)-1,3-Dimethyl-2-oxo-pyrrolidin-3-yl)-4-methoxy-phenyl]-N-methyl-acetamide 
• 136569-52-3 N-[4-Methoxy-2-((S)-3-methyl-2-oxo-tetrahydro-furan-3-yl)-phenyl]-N-methyl-acetamide 
• 136569-51-2 N-[2-((S)-2-Hydroxy-3-methyl-tetrahydro-furan-3-yl)-4-methoxy-phenyl]-N-methyl-acetamide 

Downstream Products

• 29347-10-2 physostigmine 
• 74-89-5 methylamine 
• 57-47-6 Physostigmin 
• 116103-15-2 (-)-(3aS)-1-benzyl-3a,8-dimethyl-1,2,3,3a,8,8a-hexahydro-5-methoxypyrrolo[2,3-b]indole 
• 145209-39-8 (-)-cymserine 
• 149140-55-6 1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl naphthalen-1-ylcarbamate 
• 114546-20-2 1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl 3-chlorophenylcarbamate 
• 1220811-33-5 1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl 3,5-dichlorophenylcarbamate 
• 438246-04-9 1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl 4-bromophenylcarbamate 
• 101246-67-7 1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl cyclohexylcarbamate 
• 116979-38-5 1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl 4-methoxyphenylcarbamate 
• 1220811-27-7 1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl 2,3-dichlorophenylcarbamate 
• 145209-40-1 1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl 2-chlorophenylcarbamate 
• 114546-41-7 1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-5-yl 4-chlorophenylcarbamate 

Relevant articles and documents

Nickel-Catalyzed Enantioselective Carbamoyl Iodination: A Surrogate for Carbamoyl Iodides

This work reports the enantioselective formal transfer of a carbamoyl iodide across a 1,1-disubstituted styrene using Ni-catalysis. Employing an air-stable Ni(II) precatalyst and a commercially available chiral ligand ((S)-tBuPHOX), enantioenriched 3,3-disubstituted iodooxindoles were obtained in up to 90% yield and up to 97:3 e.r. This methodology was applied to the total synthesis of (-)-esermethole and (-)-phenserine.

Synthesis of (+)-phenserine using an interrupted Fischer indolization reaction

A concise synthesis of the Alzheimer's therapeutic (+)-phenserine is described. The approach features an interrupted Fischer indolization to construct the pyrrolidinoindoline core, in addition to a classical resolution to arrive at phenserine in enantioenriched form.

Synthesis of physostigmine analogues and evaluation of their anticholinesterase activities

A series of physostigmine analogues were prepared and evaluated for cholinesterase inhibition activities, including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Most of them showed potent inhibition activities against AChE, in which compound 17 especially exhibited significantly higher selectivity over BChE than phenserine, a compound currently on clinical trial. Discussion about the relationships between structure and activity of these derivatives was also presented.

Asymmetric synthesis of pyrrolidinoindolines. Application for the practical total synthesis of (-)-phenserine

A versatile route to enantiopure 3,3-disubstituted oxindoles and 3a-substituted pyrrolidinoindolines is described in which diastereoselective dialkylation of enantiopure ditriflate 10 with oxindole enolates is the central step. These reactions are rare examples of alkylations of prostereogenic enolates with chiral sp3 electrophiles that proceed with high facial selectivity (10-20:1). The scope of this method is explored, and a model to rationalize the sense of stereoselection is advanced. This dialkylation chemistry was used to synthesize (-)-phenserine on a multigram scale in six steps and 43% overall yield from 5-methoxy-1,3-dimethyloxindole (27) and to complete a short formal total synthesis of (-)-physostigmine (2).

An efficient O-dealkylation procedure for the synthesis of (3aS,cis)- 1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo[2,3-b]indol-5-yl-3,4-dihydro- 2(1H)-isoquinolinecarboxylate

The title compound is synthesized in high yields and purity from (-)- eserethole (2a) via a lithium bromide catalyzed hydrobromic acid O- dealkylation procedure as the key step.

Catalytic asymmetric synthesis of either enantiomer of the calabar alkaloids physostigmine and physovenine

A potentially versatile asymmetric route to hexahydropyrrolo[2,3-b]indoles having carbon substituents at C-3a (Scheme 1) is demonstrated through enantioselective total syntheses of the Calabar alkaloids (-)physostigmine (2), (-)-physovenine (10), and their enantiomers. The synthesis of enantiopure (-)physostigmine proceeds from commercially available 2-butyn-1-ol (11) and N-methyl-p-anisidine (15) in 15-20% overall yield by way of eight isolated and purified intermediates. The central step is catalytic asymmetric Heck cyclization of (Z)-2-methyl-2-butenanilide 17 to-form oxindole aldehyde (S)-19 in 84% yield and 95% ee.

Method of preparation of physostigmine carbamate derivatives from eseroline ethers

The present invention relates to a novel process for the preparation of physostigmine carbamate derivatives and to pharmaceutically acceptable salts thereof. The present invention further relates to a novel process for the preparation of eseroline derivatives and to pharmaceutically acceptable salts thereof.

Method of preparation of physostigmine carbamate derivatives from eseretholes

This invention relates to a process for the preparation of a product of the formula STR1 wherein R is loweralkyl; R1, is hydrogen, loweralkyl, lowercycloalkyl, lowercycloalkylloweralkyl, lowerbicycloalkyl, aryl or arylloweralyl; R2 is lower alkyl, lowercycloalkyl, lowercycloalkylloweralkyl, lowerbicycloalkyl, aryl or arylloweralkyl; or R1 and R2 taken together with the nitrogen atom to which they are attached form a group of the formula (Ia) STR2 wherein Y is hydrogen or loweralkyl and Z is hydrogen, loweralkyl, halogen, loweralkoxy or hydroxy; X is loweralkyl, loweralkoxy, halogen or trifluoromethyl; and m is 0, 1 or 2; or a pharmaceutically acceptable salt thereof; which process comprises(a) contacting a compound of formula (II) as defined herein with fortified hydrogen bromide to afford a compound of formula (III) as defined herein; contacting the reaction mixture containing a compound of formula (III) with either (1) an isocyanate of formula R1 NCO or (2) with a compound of formula (IV) as defined to afford a compound of formula (V) as defined herein and contacting the reaction mixture containing the compound of formula (V) with an amine of the formula R1 R2 NH herein in the presence of a carboxylic acid of the formula R5 COOH and forming and isolating the product of Formula (I).

Preparation of physostigmine carbamate derivatives from physostigmine

This application relates to a new process for the preparation of a product of the formula STR1 wherein R, R1, R2, X and m are as defined within, which process comprises preparing treating a compound such as physostigmine to form eseroline which is then treated with an appropriate compound or its equivalent. Acetic acid is added to the reaction mixture after the formation of eseroline.

Method of preparation of physostigmine carbamate derivatives from eseretholes

This application relates to a new process for the preparation of a product of the formula STR1 wherein R is loweralkyl; R1 is hydrogen, loweralkyl, lowercycloalkyl, lowercycloalkylloweralkyl, lowerbicycloalkyl, aryl or arylloweralkyl; R2 is loweralkyl, lowercycloalkyl, lowercycloalkylloweralkyl, lowerbicycloalkyl, aryl or arylloweralkyl; or R1 and R2 taken together with the nitrogen atom to which they are attached from a 3,4-dihydro-2H(1H)-isoquinoline group; X is loweralkyl, loweralkoxy, halogen or trifluoromethyl; and m is 0, 1 or 2; which process comprises (a) contacting a compound of formula II STR2 wherein R, X and m are as defined above and R3 is loweralkyl, with aluminum chloride followed by tartaric acid to afford a compound of formula III STR3 wherein R, X and m are as defined above; (b) contacting the reaction mixture containing the compound of Formula III either (1) with an isocyanate of the formula R1 NCO and obtaining a product of the formula I wherein R2 is hydrogen; or (2) with a compound of formula IV STR4 wherein R4 is hydrogen or loweralkyl in the presence of a carboxylic acid of the formula wherein R5 is loweralkyl to afford a compound of formula V STR5 wherein R, R4, X and m are as above; contacting the reaction mixture containing the compound of Formula V with a compound of the formula wherein R1 and R2 are as above; and isolating the product of Formula I.