Browsing by Author "Chen, Li-Hsun"

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A concise synthesis of 2-(2-aminothiophene)-benzimidazoles by one-pot multicomponent reaction
(2013)
Chen, Li-Hsun
;
Chuang, Ying-Sheng
;
Narhe, Bharat D.
;
Sun, Chung-Ming
;
應用化學系
A one-pot synthesis of 2-aminothiophene linked benzimidazoles was achieved by utilizing 2-cyanomethyl benzimidazoles in a modified Gewald multicomponent reaction. The synthetic strategy of the reaction involved treatment of 2-(cyanomethyl)-benzimdazole with aldehydes containing an active methylene group and sulfur powder under refluxing conditions. The multicomponent reaction proceeded via Knoevenagel condensation of 2-(cyanomethyl)-benzimdazole with aldehyde to generate an alpha,beta-unsaturated nitrile followed by cyclization with molecular sulfur under basic conditions to give biologically relevant 2-(2-aminothiophene)-benzimidazoles in good yields.
A Novel Mechanistic Study on Ultrasound-Assisted, One-Pot Synthesis of Functionalized Benzimidazo[2,1-b]quinazolin-1(1H)-ones
(2016-03)
Chen, Li-Hsun
;
Chung, Tsai-Wen
;
Narhe, Bharat D.
;
Sun, Chung-Ming
;
應用化學系
Ultrasound-assisted synthesis of benzimidazo[2,1-b]quinazolin-1(1H)-ones was achieved via piperidine-catalyzed three-component reaction of 2-aminobenzimidazoles, an aromatic aldehyde, and 1,3-dione in aqueous isopropanol. This mechanism was first suspected following our identification of unusual reaction intermediates in a one-pot reaction. An unprecedented coupling reaction, it involved a nucleophilic attack by 2-aminobenzimidazole on in situ generated Michael adduct, followed by electrocyclic ring formation reaction. In contrast to the commonly accepted mechanism, that the direct reaction of 2-amino benzimidazole with a Knoevenagel adduct cannot deliver target compounds.
Divergent ionic liquid supported synthesis of isolable guanidine linked quinoxalinone and benzodiamine
(2013-02-06)
Chen, Li-Hsun
;
Xu, Zhan-Hui
;
Lin, Chun-Chung
;
Sun, Chung-Ming
;
應用化學系
Ionic liquid supported synthesis of guanidine linked piperazine, diazepane, and aminomethylpiperidine to difluoroquinoxalinones and difluoro benzodiamine was achieved by two regioisomeric products. They were isolated from one pot reduction and intramolecular cyclization to afford quinoxalinone ring system with traceless cleavage of ionic liquid support. Besides, the ionic-supported other isomer was further cleaved in methanol. All the reactions were carried out on an ionic liquid support under various conditions to deliver biologically relevant scaffolds with high purity and excellent yields. (C) 2012 Elsevier Ltd. All rights reserved.
Divergent Synthesis of Unsymmetrical Annulated Biheterocyclic Compound Libraries: Benzimidazole Linked Indolo-benzodiazepines/quinoxaline
(2011-07-01)
Chen, Li-Hsun
;
Chang, Chia-Mao
;
Salunke, Deepak B.
;
Sun, Chung-Ming
;
應用化學系
Diversity-oriented synthesis of novel benzimidazole linked indolo-benzodiazepine/quinoxaline ring systems using poly(ethylene glycol) as soluble polymer support is described. Corrunercially available 4-fluoro-3-nitrobenzoic acid and indoline were utilized for the construction of these annulated biheterocyclic compound libraries having multiple privileged structures with three-point structural diversity. A reagent based diversification approach coupled with the Pictet-Spengler-type condensation was used to construct the tetracydic indolo-benzodiazepines/quinoxalines on substituted benzimidazoles.
Enantioselective synthesis of (-)-(R) Silodosin by ultrasound-assisted diastereomeric crystallization
(2013-04-01)
Barve, Indrajeet J.
;
Chen, Li-Hsun
;
Wei, Patrick C. P.
;
Hung, Jui-Te
;
Sun, Chung-Ming
Enantioselective synthesis of clinically approved drug Silodosin for the treatment of benign prostatic hyperplasia from the commercially available compounds 1-acetyl-5-(2-aminopropyl) indoline-7-carbonitrile A and 2-(2-(2,2,2-trifluoroethoxy)phenoxy)ethyl methanesulfonate C is explored. Key step in the synthesis is chiral resolution of intermediate I, which was achieved by a simple diastereomeric crystallization using (S)-(+)-mandelic acid assisted by ultrasonication. The present synthetic strategy has lesser number of steps and is vastly improved the overall yield in this short route towards target compound Silodosin. (C) 2013 Elsevier Ltd. All rights reserved.
Microwave Promoted Simple, Efficient and Regioselective Synthesis of Trisubstituted Imidazo[1,2-a]benzimidazoles on Soluble Support
(2011-03-01)
Chen, Li-Hsun
;
Hsiao, Ya-Shan
;
Yellol, Gorakh S.
;
Sun, Chung-Ming
;
應用化學系
An efficient microwave-assisted and soluble polymer-supported synthesis of medicinally important imidazole-fused benzimidazoles has been developed. The protocol involves the rapid condensation of polymer-bound amino benzimidazoles with various alpha-bromoke-tones and subsequent in, situ intramolecular cyclization under microwave irradiation resulting in a one pot synthesis of imidazole interlacing benzimidazole polymer conjugates. The condensed product was obtained with excellent regioselectivity. The biologically interesting imidazo [1,2-a]benzimidazoles was released from polymer support at ambient temperature. Diversity in the triheterocyclic nucleus was achieved by the different substitutions at its 2, 3, and 9 positions. The new protocol has the advantages of short reaction time, easy workup process, excellent yields, reduced environmental impact, wide substrate scope and convenient procedure.
Multidisciplinary Synthetic Approach for Rapid Combinatorial Library Synthesis of Triaza-Fluorenes
(2010-09-01)
Hsiao, Ya-Shan
;
Yellol, Gorakh S.
;
Chen, Li-Hsun
;
Sun, Chung-Ming
;
應用化學系
A new multidisciplinary synthetic approach comprising polymer-support synthesis, microwave-assisted synthesis, and multicomponent condensation facilitates synthesis of triaza-fluorenes library with a set of advantages such as rapid process, simple purification, and structural diversity in one shot. Microwave-assisted multistep synthetic protocol was used to construct the benzimidazole ring on soluble polymer support using activated aryl-fluorides. The PEG anchored aryl fluoride was condensed with selective primary amines via an ipso-fluoro displacement reaction followed by reduction of nitro group. The subsequent cyclization with cyanogen bromide is used as a key step to furnish immobilized benzimidazoles. Finally multicomponent condensation of resulted polymer bound benzimidazoles with various aldehydes and 1,3-diones under microwave irradiations provides rapid access for triaza-fluorenes with high purity and excellent yields. Microwave irradiation greatly accelerates the rate of all reactions while polymer support facilitates purifications by simple precipitation technique. This strategy dramatically increases efficiency of overall multistep synthesis.
Palladium-catalyzed regioselective synthesis of 2(2 '-biphenyl)benzimidazoles through C-H activation
(2013-11-01)
Chen, Li-Hsun
;
Wu, Tz-Yi
;
Paike, Vijaykumar
;
Sun, Chung-Ming
;
應用化學系
An efficient palladium-catalyzed strategy through C-H bond activation for the synthesis of 2(2-biphenyl)-benzimidazoles is reported herein. The regioselective C-C bond formation proceeds in a sealed tube via oxidative C-H activation of ortho-directed 2-aryl-benzimidazole to couple with various iodobenzene analogs in high yields. This arylation exhibited high regioselectivity which is able to increase molecular diversity in difficult functionalized positions of parent molecules. This strategy provides a convenient and simple synthesis of biphenyl heterocyclic compounds with high regioselectivity.
Parallel synthesis and biological evolution of quinic acid derivatives as immuno-suppressing agents against T-cell receptors
(2015-01-01)
Huang, Chih-Yu
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Chen, Li-Hsun
;
Huang, Hsuan-Yu
;
Kao, Feng-Sheng
;
Lee, Yun-Ta
A simple protocol for the synthesis of quinic acid derivatives was established and their biological evolution against T-cells is studied. Results showed that one of the derivatives, Cyn-1324, has low toxicity on T-cells and a high effect on reducing Signal 2 of T-cell immune responses. In vitro binding measurements of atomic force spectroscopy further indicated that the blocking effect of Cyn-1324 between CD28 and CD80 was about 31 + 4%. In vivo animal tests also confirmed that Cyn-1324 can reduce the allergic responses from ovalbumin-induced mice with little toxicity. Based on these observations, Cyn-1324 can be a mild immuno-suppressive candidate for future drug development.
Regioselective synthesis of imidazo[1,5-a]quinoxalines and methyl N-phenylbenzimidats on an ionic liquid support
(2016-01-01)
Chen, Li-Hsun
;
Kao, Chih-Hsien
;
Dhole, Sandip
;
Barve, Indrajeet J.
;
Shen, Li-Ching
An ionic liquid (IL) supported, regioselective synthesis of imidazo[1,5-a]quinoxalines and methyl N-phenylbenzimidats under microwave conditions was reported. The IL-immobilized aromatic amines were reacted with various ketones and aliphatic aldehydes using an unconventional Pictet-Spengler reaction to generate polycyclic imidazo[1,5-a]quinoxalines. Alternatively, aromatic aldehydes afforded auto-oxidized imidazo[1,5-a]quinoxalines first which further converted to novel methyl N-phenylbenzimidats unexpectedly during the cleavage of the IL-support. In the reported strategy, rapidness is achieved through microwave conditions while the IL-support assists purification by simple precipitation.
Regioselective synthesis of imidazo[1,5-a]quinoxalines and methyl N-phenylbenzimidats on an ionic liquid support
(2016-01-01)
Chen, Li-Hsun
;
Kao, Chih-Hsien
;
Dhole, Sandip
;
Barve, Indrajeet J.
;
Shen, Li-Ching
An ionic liquid (IL) supported, regioselective synthesis of imidazo[1,5-a]quinoxalines and methyl N-phenylbenzimidats under microwave conditions was reported. The IL-immobilized aromatic amines were reacted with various ketones and aliphatic aldehydes using an unconventional Pictet-Spengler reaction to generate polycyclic imidazo[1,5-a]quinoxalines. Alternatively, aromatic aldehydes afforded auto-oxidized imidazo[1,5-a]quinoxalines first which further converted to novel methyl N-phenylbenzimidats unexpectedly during the cleavage of the IL-support. In the reported strategy, rapidness is achieved through microwave conditions while the IL-support assists purification by simple precipitation.
Soluble polymer supported divergent synthesis of tetracyclic benzene-fused pyrazino/diazepino indoles: an advanced synthetic approach to bioactive scaffolds
(2011)
Lin, Po-Tsung
;
Salunke, Deepak B.
;
Chen, Li-Hsun
;
Sun, Chung-Ming
;
應用化學系
The synthesis of indoline substituted nitrobenzene on a PEG support and its further elaboration to structurally diverse benzene-fused pyrazino/diazepino indoles is disclosed. A reagent based diversification approach coupled with Pictet-Spengler type condensation reactions furnished these fused polycyclic scaffolds. Microwave irradiation was used as a means of rate acceleration for soluble polymer-supported reactions. The efficiency of these fused heterocyclic molecules to inhibit the vascular endothelial growth factor receptor 3 (VEGFR-3) was examined in vitro using kinase receptor activation enzyme-linked immunosorbant assay (KIRA-ELISA). Based on the preliminary results obtained, a small set of potential drug candidates were identified as novel leads in this therapeutic area to be further explored as anti-metastatic agents.
Traceless polymer-supported divergent synthesis of quinoxalinones by microwave irradiation
(2012-05-06)
Shen, Chien-Hung
;
Tseng, Chih-Chung
;
Tasi, Cheng-Hsun
;
Shintre, Suhas A.
;
Chen, Li-Hsun
A novel protocol for rapid assemble of quinoxalinones framework has been demonstrated. This method incorporated with soluble polymer support provides a convenient approach for diversification of heterocyclic compounds and for easy purification via facile precipitation from reaction matrix. The key transformation of this study involves in situ reduction of aromatic nitro compound, tandem lactamization concomitant with traceless cleavage of the polymer support under microwave irradiation in a one-pot fashion. Moreover, forward synthetic routes were introduced to maximize complexity of the master intermediate on which further chemical elaboration was applied. The strategy is envisaged to apply for establishment of drug-like small-molecule libraries for high-throughput screening. (C) 2012 Elsevier Ltd. All rights reserved.
Traceless polymer-supported divergent synthesis of quinoxalinones by microwave irradiation
(2012-05-06)
Shen, Chien-Hung
;
Tseng, Chih-Chung
;
Tasi, Cheng-Hsun
;
Shintre, Suhas A.
;
Chen, Li-Hsun
A novel protocol for rapid assemble of quinoxalinones framework has been demonstrated. This method incorporated with soluble polymer support provides a convenient approach for diversification of heterocyclic compounds and for easy purification via facile precipitation from reaction matrix. The key transformation of this study involves in situ reduction of aromatic nitro compound, tandem lactamization concomitant with traceless cleavage of the polymer support under microwave irradiation in a one-pot fashion. Moreover, forward synthetic routes were introduced to maximize complexity of the master intermediate on which further chemical elaboration was applied. The strategy is envisaged to apply for establishment of drug-like small-molecule libraries for high-throughput screening. (C) 2012 Elsevier Ltd. All rights reserved.