- Chiral Bicyclic Imidazole-Catalyzed Acylative Dynamic Kinetic Resolution for the Synthesis of Chiral Phthalidyl Esters
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Utilizing a chiral bicyclic imidazole organocatalyst and adopting a continuous injection process, an alternative route has been developed for the efficient synthesis of chiral phthalidyl ester prodrugs via dynamic kinetic resolution of 3-hydroxyphthalides through enantioselective acylation (up to 99 % ee). The computational studies suggest a general base catalytic mechanism differing from the widely accepted nucleophilic catalytic mechanism. The structure analysis of the key transition states shows that the CH-π interactions and not the previously considered cation/π-π interactions between the catalyst and substrate is the dominant factor giving rise to the observed stereocontrol.
- Zhou, Muxing,Gridneva, Tatiana,Zhang, Zhenfeng,He, Ende,Liu, Yangang,Zhang, Wanbin
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p. 1641 - 1645
(2020/11/30)
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- Synthesis and SAR of 2,3,3a,4-tetrahydro-1H-pyrrolo[3,4-c]isoquinolin- 5(9bH)-ones as 5-HT2C receptor agonists
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A series of 2,3,3a,4-tetrahydro-1H-pyrrolo[3,4-c]isoquinolin-5(9bH)-ones is described, several examples of which exhibit potent 5-HT2C agonism with excellent selectivity over the closely related 5-HT2A and 5-HT2B receptors. Compounds such as 38 and 44 were shown to be effective in reducing food intake in an acute rat feeding model.
- Fevig, John M.,Feng, Jianxin,Rossi, Karen A.,Miller, Keith J.,Wu, Ginger,Hung, Chen-Pin,Ung, Thao,Malmstrom, Sarah E.,Zhang, Ge,Keim, William J.,Cullen, Mary Jane,Rohrbach, Kenneth W.,Qu, Qinling,Gan, Jinping,Pelleymounter, Mary Ann,Robl, Jeffrey A.
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p. 330 - 335
(2013/02/25)
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- Functionalization of 3-chlorobenzaldehyde
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2-Substituted 3-chlorobenzaldehydes were prepared from the corresponding 2-(3-chlorophenyl)-1,3-dioxolanes using an ortho-lithiation strategy. The 6-chloro-2-formylbenzamide exists only in a ring form, but 6-chloro-2- formylbenzoic acid esters were isolated in both forms as open chain and cyclic tautomers. 7-Chloro-3-hydroxy-3H-isobenzofuran-1-one reacted with nucleophilic reagents at the carbonyl or quaternary carbon depending on the character of nucleophile. Georg Thieme Verlag Stuttgart New York.
- Aksjonova, Kristine,Belyakov, Sergey,Liepinsh, Edvards,Boman, Arne,Lundstedt, Torbjorn,Lek, Per,Trapencieris, Peteris
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p. 2200 - 2208
(2012/09/22)
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- Synthesis and biological activity of n-butylphthalide derivatives
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A series of n-butylphthalide derivatives were designed and synthesized. The in vitro activities of these compounds were evaluated by a resting tension of isolated rat thoracic aorta ring assay. Compounds 4g and 4i were found to be more active than n-butylphthalide.
- Wang, Wei,Cha, Xue-Xiang,Reiner, John,Gao, Yuan,Qiao, Hai-Ling,Shen, Jia-Xiang,Chang, Jun-Biao
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experimental part
p. 1941 - 1946
(2010/06/19)
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- Discovery of (R)-9-ethyl-1,3,4,10b-tetrahydro-7-trifluoromethylpyrazino[2, 1-a]isoindol-6(2H)-one, a selective, orally active agonist of the 5-HT 2C receptor
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Robust pharmaceutical treatment of obesity has been limited by the undesirable side-effect profile of currently marketed therapies. This paper describes the synthesis and optimization of a new class of pyrazinoisoindolone- containing, selective 5-HT2C agonists as antiobesity agents. Key to optimization of the pyrazinoisoindolone core was the identification of the appropriate substitution pattern and functional groups which led to the discovery of (R)-9-ethyl-1,3,4,10b-tetrahydro-7-trifluoromethylpyrazino[2,1-a] isoindol-6(2H)-one (58), a 5-HT2C agonist with > 300-fold functional selectivity over 5-HT2B and > 70-fold functional selectivity over 5-HT2A. Oral dosing of 58 reduced food intake in an acute rat feeding model, which could be completely reversed by a selective 5-HT2C antagonist and caused a reduction in body weight gain in a 4-day rat model.
- Wacker, Dean A.,Varnes, Jeffrey G.,Malmstrom, Sarah E.,Cao, Xueying,Hung, Chen-Pin,Ung, Thao,Wu, Ginger,Zhang, Ge,Zuvich, Eva,Thomas, Michael A.,Keim, William J.,Cullen, Mary Jane,Rohrbach, Kenneth W.,Qu, Qinling,Narayanan, Rangaraj,Rossi, Karen,Janovitz, Evan,Lehman-McKeeman, Lois,Malley, Mary F.,Devenny, James,Pelleymounter, Mary Ann,Miller, Keith J.,Robl, Jeffrey A.
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p. 1365 - 1379
(2007/10/03)
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- Ortholithiation of unprotected benzoic acids: Application for novel 2-chloro-6-substituted benzoic acid syntheses
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2-Chloro-6-substituted benzoic acids of the type 2a-h were prepared by the tandem metallation sequence from 2-chlorobenzoic acid 1 with the 1:1 complex secbutyllithium/TMEDA in THF at -78°C followed by quenching with electrophiles.
- Gohier, Frederic,Castanet, Anne-Sophie,Mortier, Jacques
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p. 799 - 806
(2007/10/03)
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