Browsing by Author "Yellol, Gorakh S."

Now showing 1 - 14 of 14

Base-Catalyzed Povarov Reaction: An Unusual [1,3] Sigmatropic Rearrangement to Dihydropyrimidobenzimidazoles
(2011-10-07)
Chen, Chih-Hau
;
Yellol, Gorakh S.
;
Lin, Po-Tsung
;
Sun, Chung-Ming
;
應用化學系
A novel base-catalyzed Povarov reaction of arylamines, aldehydes, and electron-deficient dienophiles has been developed. An unprecedented in situ [1,3] sigmatropic rearrangement leading to 4,10-dihydropyrimido[1,2-a]benzimidazoles has also been discovered. An insight of the plausible mechanism is discussed and supported by X-ray crystal study. This cascade reaction is achieved in a one-pot multicomponent fashion on soluble support under microwave conditions.
Diastereoselective Synthesis of Bridged Polycyclic Alkaloids via Tandem Acylation/Intramolecular Diels-Alder Reaction
(2013-10-04)
Chen, Chih-Hau
;
Yellol, Gorakh S.
;
Tsai, Cheng-Hsun
;
Dalvi, Prashant B.
;
Sun, Chung-Ming
A mild and efficient stereoselective synthesis of hexacyclic indole alkaloids with a tetrahydro-beta-carboline motif has been developed by utilizing the Pictet-Spengler reaction and tandem N-acylation followed by intramolecular Diels-Alder cyclization. Initially, a diene unit was installed in the tetrahedron beta-carboline skeleton through Pictet-Spengler cyclization of the corresponding aldehyde with tryptophan ester. The dienophile moiety was introduced by N-acylation of tetrahydro-beta-carboline. Successive, in situ, [4 + 2] intramolecular Diels-Alder cycloaddition of the activated dienophile and conjugated diene containing intermediate furnished bridged polycyclic heterocycles with high diastereoselectivity. Formation of four new rings, five new covalent bonds, and five new chiral centers with excellent stereoselectivity is the key, feature of this strategy. The diastereoselective formation of product was attributed to intramolecular chirality transfer through a chiral amino acid. The stereoselective outcome of this tandem reaction was confirmed by X-ray crystallographic studies. The developed synthetic strategy was also explored on a soluble polymer support to incorporate the advantage of rapid synthesis and a high throughput workup process toward the development of a green synthetic protocol for polycyclic alkaloids.
Ionic liquid supported multistep divergent synthesis of benzimidazole linked pyrrolo-/pyrido-/isoindolo-benzimidazolones
(2011-06-01)
Thummanagoti, Suman
;
Yellol, Gorakh S.
;
Sun, Chung-Ming
;
應用化學系
;
Department of Applied Chemistry
Diversity oriented parallel synthesis for bis-heterocyclic skeletal novel benzimidazole linked pyrrolo-/pyrido-benzimidazolones and benzimidazole linked isoindolo-benzimidazolones has been developed on ionic liquid support under microwave irradiation by utilizing the cascade cyclization. The key tandem transformation comprises (i) amino-alkylation of immobilized o-phenylenediamine with ketoacids, (ii) intramolecular cyclization through secondary amine on electrophilic imine carbon toward pentacyclic aza-ring and (iii) second amido-cyclization to deliver cycloamide ring. The synergy arises by combined use of microwave heating with ionic liquid support which is very effectively used to speed up multistep synthesis of biological interesting heterocycles. (C) 2011 Elsevier Ltd. All rights reserved.
Microwave assisted straightforward synthetic method for benzimidazole linked quinoxalinones on soluble polymer support
(2011-03-18)
Chou, Cheng-Ting
;
Yellol, Gorakh S.
;
Chang, Wong-Jin
;
Sun, Mei-Lian
;
Sun, Chung-Ming
The simple and efficient method was developed for the synthesis of benzimidazole linked quinoxalinones on soluble polymer support using microwave conditions. The acid catalyzed condensation of 4-fluoro-3-nitrobenzoic acid with polymer immobilized o-phenylenediamine, ipso-fluoro nucleophilic substitution with various primary amines and cyclization with acetyl chloride are the key steps involved in implemented linear synthesis. In key cyclization step, the regioselective N-acylation at secondary amine with chloroacetyl chloride followed by spontaneous intramolecular ring closure through ortho-amine functionality generate the quinoxaline skeleton under microwave irradiation. The removal of polymer support and exposure of quinoxalines for auto-oxidation finally produce the benzimidazole linked quinoxalinone derivatives with high purity and yields. (C) 2011 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.
Microwave-Assisted Tandem Transformation on an Ionic-Liquid Support: Efficient Synthesis of Pyrrolo/Pyridobenzimidazolones and Isoindolinone-Fused Benzimidazoles
(2011-09-05)
Thummanagoti, Suman
;
Yellol, Gorakh S.
;
Sun, Chung-Ming
;
應用化學系
;
Department of Applied Chemistry
A tandem transformation that involves the formation of three bonds and two heterocyclic rings in a one-pot fashion through amino-alkylation of an ionic-liquid-immobilized diamine with keto acids followed by successive double intramolecular cyclizations to afford a tricyclic framework has been explored. This tandem cyclization has been utilized to develop a rapid and efficient method to synthesize various pyrrolo[1,2-a]benzimidazolones and pyrido[1,2-a]benzimidazolones on an ionic-liquid support by using focused microwave irradiation. The application of this tandem cyclization was further extended to the aromatic keto acids to provide isoindolinone-fused benzimidazoles, a structurally heterogeneous library with skeletal diversity. The outcome of the cascade reaction was confirmed by the X-ray crystallographic study of the product directly attached to the ionic-liquid support. Use of the ionic liquid as a soluble support facilitates purification by simple precipitation along with advantages like high loading capacity, homogeneous reaction conditions, and monitoring of the reaction progress by regular conventional spectroscopic methods, whereas application of microwave irradiation greatly accelerates the rate of the reactions.
Microwave-Enhanced Efficient Regioselective Synthesis of 1,3,4-Trisubstituted 2-Mercaptoimidazoles on a Soluble Support
(2012-01-01)
Yellol, Gorakh S.
;
Chou, Cheng-Ting
;
Chang, Wang-Jin
;
Maiti, Barnali
;
Sun, Chung-Ming
A novel efficient synthetic method for regioselective synthesis of optically active 2-mercaptoimidazoles with three points of structural diversity was investigated on a polyethylene glycol (PEG) support. The key synthetic steps involve (i) synthesis of thiourea derivatives of polymer-supported amino acids with isothiocyanates and (ii) one-pot regioselective condensation of PEG-linked thiourea with a-bromo ketones to furnish the 2-mercaptoimidazole skeleton under microwave conditions. An excellent regioselectivity was observed during this one-pot condensation reaction which was further supported by NOE studies. In addition to three sets of structural diversity, supplementary chirality at the a-position of the 2-mercaptoimidazole skeleton is the key feature of this synthesis. A representative set of 2-mercaptoimidazoles was efficiently assembled on soluble support utilizing various L-amino acids, isothiocyanates and a-bromoaryl ketones with good yields.
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.
Novel cyclization of bis-Boc-guanidines: expeditive traceless synthesis of 1,3,5-oxadiazinones under microwave conditions
(2010)
Yellol, Gorakh S.
;
Chung, Tsai-Wen
;
Sun, Chung-Ming
;
應用化學系
;
Department of Applied Chemistry
A novel intramolecular cyclization was discovered during the reaction of soluble polymer supported bis-Boc-guanidines with amines under microwave irradiation, leading to an oxadiazinone skeleton. The cyclized polymer conjugates have been further utilized to generate substituted 1,3,5-oxadiazinones by a traceless synthesis.
Polymer supported synthesis of novel benzoxazole linked benzimidazoles under microwave conditions: In vitro evaluation of VEGFR-3 kinase inhibition activity
(2011)
Chanda, Kaushik
;
Maiti, Barnali
;
Yellol, Gorakh S.
;
Chien, Ming-Hsien
;
Kuo, Min-Liang
An efficient soluble polymer-supported method has been developed for the parallel synthesis of substituted benzimidazole linked benzoxazoles using focused microwave irradiation. The key step involves the amidation of 4-hydroxy-3-nitrobenzoic acid with polymer-immobilized o-phenylenediamine. Application of mild acidic conditions promoted the ring closure to furnish the benzimidazole ring. After hydrogenation of the nitro-group to amine, the resulted polymer conjugates underwent efficient ring closure with various alkyl, aryl and heteroaryl isothiocyanates to generate the polymer-bound benzimidazolyl benzoxazoles. The polymer-bound compounds were finally cleaved from the support to furnish benzimidazole linked benzoxazole derivatives. The efficacy of the resultant angular bis-heterocyclic library was studied against vascular endothelial growth factor receptor (VEGFR-3). The preliminary screening of these novel compounds exhibits moderate to high inhibition (IC(50) = 0.56-1.42 mM). This protocol provides an easy access to novel angular bis-heterocycles which have potential for the discovery of novel leads for targeted cancer therapeutics.
Regioselective, Unconventional Pictet-Spengler Cyclization Strategy Toward the Synthesis of Benzimidazole-Linked Imidazoquinoxalines on a Soluble Polymer Support
(2011-06-06)
Chen, Chih-Hau
;
Kuo, Jaren
;
Yellol, Gorakh S.
;
Sun, Chung-Ming
;
應用化學系
A novel strategy for an unconventional Pictet-Spengler reaction has been developed for the regioselective cyclization of the imidazole ring system at the C2 position. The developed strategy was utilized to develop a diversity-oriented parallel synthesis for bis(heterocyclic) skeletal novel analogs of benzimidazole-linked imidazoquinoxalines on a soluble polymer support under microwave conditions. Condensation of polymer-immobilized o-phenylenediamines with 4-fluoro-3-nitrobenzoic acid followed by nucleophilic aromatic substitution with an imidazole motif affords bis(heterocyclic) skeletal precursors for the Pictet-Spengler reaction. The unconventional Pictet-Spengler cyclization with various aldehydes was achieved regioselectively at the C2 position of the imidazole ring to furnish rare imidazole-fused quinoxaline skeletons. During the Pictet-Spengler cyclization, aldehydes bearing electron-donating groups afford 4,5-dihydro-imidazoquinoxalines, which then auto-aromatize into benzimidazole-linked imidazo[1,2-a]quinoxalines. However, interestingly, aldehydes bearing electron-withdrawing groups directly provide aromatized imidazo[1,2-a]quinoxalines, which unexpectedly afford novel benzimidazole-linked 4-methoxy-4,5-dihydro-imidazo[1,2-a] quinoxalines after polymer cleavage.
SIMPLE AND EFFICIENT ONE POT SYNTHETIC PROTOCOL TO CONSTRUCT MORPHOLIN-2-ONES
(2010-12-31)
Yellol, Gorakh S.
;
Mohapatra, Debendra K.
;
Gurjar, Mukund K.
;
Sun, Chung-Ming
;
應用化學系
A new one pot synthetic method to construct 3-substituted morpholine-2-one derivatives is presented. Amino acids refluxed with 1,2-dibromoethane and potassium carbonate in acetonitrile followed by treatment with benzyl bromide in same pot furnished the 3-substituted N-benzyl-morpholine-2-ones in good yields. The simplicity of the reaction conditions and versatility of resulted scaffold to generate wide variety of molecules makes this method more attractive for synthetic organic chemists.
Synthesis of Aminofuran-Linked Benzimidazoles and Cyanopyrrole-Fused Benzimidazoles by Condition-Based Skeletal Divergence
(2017-07-01)
Hsu, Wei-Shun
;
Tsai, Min-Huan
;
Barve, Indrajeet J.
;
Yellol, Gorakh S.
;
Sun, Chung-Ming
A condition-based skeletal divergent synthesis was explored to achieve skeletal diversity in two component condensation reaction. Cyanomethyl benzimidazole was reacted with alpha-bromoketone under thermal conditions to furnish 2-aminofuranyl-benzimidazoles, while the same reaction afforded 3-cyano-benzopyrrolo-imidazoles under microwave irradiation. Two nonequivalent nucleophilic centers on benzimidazole moiety were manipulated elegantly by different reaction conditions to achieve the skeletal diversity.
Traceless synthesis of diketopiperazine fused tetrahydro-beta-carbolines on soluble polymer support
(2011-05-01)
Chanda, Kaushik
;
Chou, Cheng-Ting
;
Lai, Jin-Ji
;
Lin, Shu-Fen
;
Yellol, Gorakh S.
The Pictet-Spengler reaction, using polyethylene glycol immobilized tryptophan ester with a variety of ketones, was achieved by refluxing condition in acidic chloroform. The linear as well as cyclic ketones were employed. All the ketones were reacted within 6-8 h to furnish soluble polymer-supported tetrahydro-beta-carboline in good yields. Further expansion at N-terminus of tetrahydro-beta-carbolines was achieved through a reaction with chloroacetyl chloride. Finally, the 2,5-diketopiperazine skeleton was constructed over a beta-carboline by amination of the resulting N-chloroacetamides and subsequent intramolecular cyclization leading to cleavage of the polymer; constitutes a traceless synthesis of tetracyclic molecular architecture. Significantly, this strategy affords a straightforward and efficient approach for the construction of biological promising molecules with high purity and good yields.