Browsing by Author "Chanda, Kaushik"

Now showing 1 - 11 of 11

Convergent Solution Phase Synthesis of Chimeric Oligonucleotides by a 2+2 and 3+3 Phosphoramidite Strategy
(2010)
Chen, Chih-Hau
;
Chen, Wei-Yu
;
Chen, Yu-Chie
;
Lee, Ming-Juan
;
Huang, Chyuan-Der
A chimeric oligonucleotide tetramer and hexamer were synthesized by the phosphoramidite approach using a 2+2 and 3+3 strategy, respectively. The concept of convergent synthesis provides an efficient route toward the synthesis of longer chimeric oligonucleotides, such as small interfering RNA oligonucleotides without the pollution of n - 1 or shorter failures. This methodology offers an efficient and economical way to scale-up the synthesis of high purity oligonucleotides for clinical trials and commercial uses.
Design, synthesis and diversification of natural product-inspired hydantoin-fused tetrahydroazepino indoles
(2015-01-01)
Barve, Indrajeet J.
;
Dalvi, Prashant B.
;
Thikekar, Tushar Ulhas
;
Chanda, Kaushik
;
Liu, Yu-Li
A facile and efficient synthesis of novel oxo, thio and seleno hydantoin fused tetrahydroazepino [4,5-b] indoles was reported. A naturally occurring iboga class alkaloid inspired seven-membered azepino[4,5-b] indole ring was synthesized as a new scaffold through Pictet-Spengler reaction followed by skeletal rearrangement of the aziridine ring. To improve the efficiency of the synthetic route, the double bond of the rearranged olefinic product 5 was reduced and a privileged hydantoin moiety was constructed on the core system through urea formation using a variety of isocyanates, isothiocyanates and isoselenocyanates followed by intramolecular cyclization to incorporate elements of diversity. The regeneration of the double bond of intermediate 9 afforded hydantoin-fused tetrahydroazepino [4,5-b] indoles.
Enantioselective Synthesis of Benzimidazolyl Quinoxalinones on Soluble Polymer Support Using Focused Microwave Irradiation
(2009-03-01)
Chanda, Kaushik
;
Kuo, Jaren
;
Chen, Chih-Hau
;
Sun, Chung-Ming
;
應用化學系
Focused microwave irradiation has been applied to a multistep synthetic sequence of reactions designed to generate benzimidazolyl quinoxalinones using a soluble polymer support. They were obtained by the ipso-fluoro (S(N)Ar) displacement of the immobilized ortho-nitro fluoro benzimidazoles with chiral alpha amino esters under microwave irradiation. Intermediate chiral organic-polymer conjugates when subjected to neutral reduction underwent a spontaneous intramolecular ring closure. Cleavage of the polymer support, at room temperature, did not cause any significant racemization resulting in the generation of a chiral molecular library with two points of structural diversity.
Microwave Controlled Reductive Cyclization: A Selective Synthesis of Novel Benzimidazole-alkyloxypyrrolo[1,2-a]quinoxalinones
(2015-05-01)
Dhole, Sandip
;
Selvaraju, Manikandan
;
Maiti, Barnali
;
Chanda, Kaushik
;
Sun, Chung-Ming
An efficient cascade synthesis of novel benzimidazole linked alkyloxypyrrolo[1,2-a]quinoxalinones was explored on soluble polymer support under micro-Wave irradiation. Two exclusive protocols have been developed for the partial and reductive cyclization by Controlling the microwave energy, Commencing from the smile substrate, ortho nitro, pyrrol: carboxylates, N-hydroxy pyrroloquinoxalinones were obtained by,, partial reductive cyclization (60 degrees C, 7 min), and the synthesis of pyrroloquinoxalinones was accomplished by full reductive, cyclization (85 degrees C, 12 min). This method represents the first synthesis N-hydroxy pyrroloquinoxalinones using Pd/C and ammonium formate as reducing agents: Further employing a variety Of alkyl bromides, the obtained pyrroloquinoxalinones were transformed to their corresponding O-, and N-alkylated analogues to deliver the diversified, novel molecular entities.
Microwave-Assisted Linear Approach Toward Highly Substituted Benzo[d]oxazol-5-yl-1H-benzo[d]imidazole on Ionic Liquid Support
(2012-02-01)
Chanda, Kaushik
;
Maiti, Barnali
;
Tseng, Chih-Chung
;
Sun, Chung-Ming
;
應用化學系
A novel and efficient diversity-oriented synthetic approach was employed to access the benzo[d]oxazol-5-yl-1H-, benzo[d]imidazole on ionic liquid support, which helps to absorb microwave irradiation. In this paper, we successfully coupled 4- hydroxy-3-nitrobenzoic acid onto ionic liquid-immobilized o-phenylehediaimine which subsequently underwent an acid mediated, ring closure reaction leading to benzimidazole derivatives. After hydrogenation of the nitro group to an amine, the resulting ionic liquid conjugate was reacted with 1,1-thiocarbonyldiimidazols to yield an ionic liquid tagged-benzoxazol, Final skeletal diversity of the present scaffold was further achieved by S-alkylation with alkyl and aryl bromides. The benzo[d]oxazol-5-, yl-1H-benzo[d]imidazole was finally cleaved smoothly from the ionic liquid support with sodium methoxide in methanol under microwave irradiation. This methodology has provided access to a small, diverse library by straightforward and simple operations and could be applied readily in various drug discovery programs.
Microwave-Assisted Synthesis of Tetracyclic 2,5-Diketopiperazines on a Soluble Polymer Support: A Structural Analogue of Tadalafil
(2009)
Chang, Wong-Jin
;
Chanda, Kaushik
;
Sun, Chung-Ming
;
應用化學系
;
Department of Applied Chemistry
Structural analogues of tadalafil that contain two diversity points have been synthesized from a soluble polymer support employing a Pictet-Spengler reaction using focussed microwave irradiation. Polymer-bound deprotected tryptophan reacts with various aldehydes to generate the tetrahydro-beta-carbolines on the support. Subsequently immobilized tetrahydro-beta-carboline underwent a highly efficient intramolecular N-heterocyclization in a traceless fashion from various in-situ generated alpha-alkyl and heteroalkyl amides in two steps to generate tetracyclic 2,5-diketopiperazines in high purity. All the compounds were isolated as cis and trans isomers with good yields.
Multicomponent Solvent-Free Synthesis Of Benzimidazolyl Imidazo[1,2-a]-pyridine Under Microwave Irradiation
(2013-06-01)
Maiti, Barnali
;
Chanda, Kaushik
;
Selvaraju, Manikandan
;
Tseng, Chih-Chung
;
Sun, Chung-Ming
A novel one-pot, three-component reaction employing variously substituted benzimidazole-linked amino pyridines, aldehydes, and isonitriles catalyzed by scandium(III) triflate under solvent-free conditions were accomplished. This new synthetic methodology facilitates the rapid generation of intricate molecular frameworks in three-dimensional fashion leading to benzinaidazole-imidazo [1,2-a] pyridines. This approach is envisioned as an environmentally benign process and a simple operation to the biological interesting compounds. The present synthetic sequence permits the introduction of three points of structural diversity to expand chemical space with high purity and excellent yields.
Novel approach towards 2-substituted aminobenzimidazoles on imidazolium ion tag under focused microwave irradiation
(2011-08-26)
Chanda, Kaushik
;
Maiti, Barnali
;
Chung, Wen-Sheng
;
Sun, Chung-Ming
;
應用化學系
We have developed an efficient, parallel synthesis of 2-substituted aminobenzimidazoles via intramolecular ring closing reactions of imidazolium ion tag immobilized o-phenylenediamine with various isothiocyanates. The methodology is based on the attachment of 4-fluoro-3-nitro benzoic acid into the imidazolium ion tag, which enables the S(N)Ar reactions with different amines followed by neutral reduction to furnish o-phenylenediamines under microwave irradiation. The substituted isothiocyanates are reacted with o-phenylenediamines to form monothiourea, which is further activated by methyl iodide to undergo desulfurization in one pot manner. The ionic liquid bound 2-substituted aminobenzimidazoles were finally cleaved from the support with sodium methoxide to generate target compounds in good yields and high purities with two points of structural diversity. This synthetic protocol has promising features of extremely short reaction time, operational simplicity, good yields, as well as widespread applications, leading to a facile and straightforward admittance to structurally diverse 2-substituted aminobenzimidazole analogues with potential bioactivities. (C) 2011 Elsevier Ltd. All rights reserved.
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.
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.
Traceless Synthesis of Hydantoin Fused Tetrahydro-beta-carboline on Ionic Liquid Support in Green Media
(2009-11-05)
Maiti, Barnali
;
Chanda, Kaushik
;
Sun, Chung-Ming
;
應用化學系
;
Department of Applied Chemistry
A novel ionic liquid (IL) supported, green synthetic protocol has been developed toward the synthesis of oxo and thio hydantoin analogues tethered with tetrahydro-beta-carboline by the use of focused microwave irradiation. IL-bound tryptophan underwent a Pictet-Spengler reaction with various carbonyl compounds to generate the IL-immobilized tetrahydro-beta-carbolines in aqueous isopropanol media. Subsequent reaction of substituted tetra hydro-beta-carboline derivatives with various isocyanates and isothiocyanate provided a three-dimensional combinatorial library in a traceless fashion.