- 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.
- Abel-Snape, Xavier,Glorius, Frank,Lautens, Mark,Marchese, Austin D.,Mirabi, Bijan,Whyte, Andrew,Wollenburg, Marco
-
p. 4780 - 4785
(2020/05/19)
-
- 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.
- Schammel, Alex W.,Chiou, Grace,Garg, Neil K.
-
supporting information; experimental part
p. 725 - 728
(2012/03/26)
-
- 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.
- Zhan, Zha-Jun,Bian, Hong-Ling,Wang, Jian-Wei,Shan, Wei-Guang
-
scheme or table
p. 1532 - 1534
(2010/06/21)
-
- 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).
- Huang, Audris,Kodanko, Jeremy J.,Overman, Larry E.
-
p. 14043 - 14053
(2007/10/03)
-
- 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.
- Gao, Zhongli,Lee, Thomas B. K.,Rauckman, Barbara S.
-
p. 331 - 333
(2007/10/03)
-
- 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.
- Matsuura, Takaharu,Overman, Larry E.,Poon, Daniel J.
-
p. 6500 - 6503
(2007/10/03)
-
- 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.
- -
-
-
- Memory enhancing and analgesic 1,2,3a,8,8a-hexahydro-3a,8(and 1,3a,8)-di(and tri)methylpyrrolo[2,3-b]indoles
-
There are disclosed various derivatives of eseroline and related compounds of the formula below STR1 where R,R1, X,Z and m are as defined in the specification, which compounds being useful for enhancing cholinergic function, as antidepressant agents and as analgesic agents.
- -
-
-
- Enantiocontrolled Total Syntheses of (-)-Physovenine and (-)-Physostigmine
-
Enantiocontrolled total syntheses of the Calabar bean alkaloid (-)-physovenine (1) and (-)-physostigmine (2) have been achieved in a concise manner starting from the optically active tricyclic enone 3 employing a Fischer indolization reaction under nonacidic conditions as the key step.
- Takano, Seiichi,Moriya, Minoru,Ogasawara, Kunio
-
p. 5982 - 5984
(2007/10/02)
-
- Memory enhancing and analgesic 1,2,3,3A,8,8A-hexahydro-3A,8 (and) 1,3A,8)-di(and tri)methylpyrrolo(2,3-B)indoles, compositions and use
-
There are described compounds of the formula STR1 where (a) X is O or S; (b) R is H, loweralkyl, STR2 where Y is O or S; R2 is alkyl, cycloalkyl, bicycloalkyl, cycloalkenyl, aryl, arylloweralkyl, heteroaryl or heteroarylloweralkyl, R3 is H or alkyl, or the group --NR2 R3 taken as a whole is 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl, 4-thiomorpholinyl, 1-piperazinyl, 4-methyl-1-piperazinyl or 2-(2,6-dichlorophenylimino)-1-imidazolidinyl) and R4 is hydrogen, loweralkyl, arylloweralkyl, diarylloweralkyl, aryl or heteroaryl, (c) m is 1 or 2; (d) each Z is independently H, loweralkyl, halogen, nitro, --NH2, loweralkylcarbonylamino, arylcarbonylamino, loweralkoxycarbonylamino or loweralkylamino, and (e) R1 is H, loweralkyl, arylloweralkyl, heteroarylloweralkyl, cycloalkylmethyl or loweralkenylmethyl, with the proviso that when X is O, m is 1, Z is H and R1 is methyl, R is not --CONHCH3, --CONHC6 H5, hydrogen, methyl or ethyl, and that when X is O, m is 1 and Z and R1 are both hydrogen, R is not hydrogen or methyl, and pharmaceutically acceptable acid addition salts thereof which are useful as memory-enhancing and analgesic agents.
- -
-
-
- PRACTICAL SYNTHESIS OF UNNATURAL (+)-PHYSOSTIGMINE AND CARBAMATE ANALOGUES
-
Details of a synthesis of unnatural (+)-physostigmine (5) prepared from urea 1 via (+)-eseroline (4) are given.Preparation of (+)-octylcarbamate 6, (+)-benzylcarbamate 7, (+)-phenylcarbamate 8 and (+)-N-methylphysostigmine (9) from (+)-eseroline (4) is also described.
- Yu, Qian-Sheng,Brossi, Arnold
-
p. 745 - 750
(2007/10/02)
-
- Comparison of (-)-Eseroline with (+)-Eseroline and Dihydroseco Analogues in Antinociceptive Assays: Confirmation of Rubreserine Structure by X-ray Analysis
-
The enantiomers of eseroline bind to opiate receptors of rat brain membranes with equal affinities and show opiate agonist properties as inhibitors of adenylate cyclase in vitro.However, only (-)-eseroline shows potent narcotic agonist activity in vivo, similar to that of morphine.Neither (-)-noreseroline, (+)-eseroline, nor the open dihydroseco analogue (-)-8 shows analgetic effects in vivo.The structure of rubreserine being a resonance hybrid of an o-quinone with its zwitterionic mesomer is confirmed by solid-state X-ray diffraction analysis.
- Schoenenberger, Bernhard,Jacobson, Arthur E.,Brossi, Arnold,Streaty, Richard,Klee, Werner A.,et al.
-
p. 2268 - 2273
(2007/10/02)
-
- Synthesis of some quaternary ammonium alkylating agents and their effects on soman-inhibited acetylcholinesterase
-
A number of compounds were synthesized and tested for their ability to realkylate the phosphonate anion of 'aged', soman-inhibited acetylcholinesterase. None were found able to do so, but two of the compounds in particular, [2-(4-pyridyl)ethyl]diethylmethylammonium iodide and its 2-isomer, proved able to slow the rate of aging significantly.
- Gray,Platz,Chang,Leverone,Ferrick,Kramer
-
p. 111 - 116
(2007/10/02)
-