Browsing by Author "Chang, Chia-Mao"

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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.
Parallel synthesis of 2-sulphanylated bis-benzimidazoles on soluble polymer support
(2008-05-01)
Chang, Chia-Mao
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Kulkarni, Manohar V.
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Chen, Chih-Hau
;
Wang, Chi-Hsiang
;
Sun, Chung-Ming
A well-sustained multistep synthetic protocol has been designed for the PEG-functionalized aromatic acid amide to generate a molecular library of 2-alkylthio bis-benzimidazoles. An attempted synthesis of benzimidazole-2-thiol in dichloromethane has led to S-chloromethyl methyl sulfides, mimicking bacterial enzymatic systems. Regioselective S-alkylation was brought about under controlled conditions using a mild base at room temperature. The polymer-free compounds, 2-sulfanylated bisbenzimidazoles, were obtained in high yields and high purities. Chemical shift changes in proton and carbon NMR-have been employed to monitor the progress of the reaction steps and to prove the site of S-alkylation, respectively.
Qualitative analysis of the fluorophosphonate-based chemical probes using the serine hydrolases from mouse liver and poly-3-hydroxybutyrate depolymerase (PhaZ) from Bacillus thuringiensis
(2012-11-01)
Huang, Yi-Long
;
Chung, Tsai-Wen
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Chang, Chia-Mao
;
Chen, Chih-Hau
;
Liao, Chen-Chung
The serine hydrolase family consists of more than 200 members and is one of the largest enzyme families in the human genome. Although up to 50 % of this family remains unannotated, there are increasing evidences that activities of certain serine hydrolases are associated with diseases like cancer neoplasia, invasiveness, etc. By now, several activity-based chemical probes have been developed and are applied to profile the global activity of serine hydrolases in diverse proteomes. In this study, two fluorophosphonate (FP)-based chemical probes were synthesized. Further examination of their abilities to label and pull down serine hydrolases was conducted. In addition, the poly-3-hydroxybutyrate depolymerase (PhaZ) from Bacillus thuringiensis was demonstrated as an appropriate standard serine hydrolase, which can be applied to measure the labeling ability and pull-down efficiency of FP-based probes. Furthermore, mass spectrometry (MS) was used to identify the serine residue that covalently bonded to the active probes. Finally, these FP-based probes were shown capable of establishing the serine hydrolase profiles in diverse mouse tissues; the serine hydrolases pulled down from mouse liver organ were further identified by MS. In summary, our study provides an adequate method to evaluate the reactivity of FP-based probes targeting serine hydrolases.
Scaffold-directed traceless synthesis of tetrahydro-beta-carbolinehydantoins
(2007-07-01)
Chen, Chih-Hau
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Chang, Chia-Mao
;
Chen, Hsia-Yuan
;
Lai, Jin-Ji
;
Sun, Chung-Ming
Pharmacologically interesting tetrahydro-beta-carbolinehydantoins have been prepared through four-step traceless synthesis by a combinatorial approach. Two-arm PEG 1 (MW approximate to 4000) was used as a soluble polymer support and reacted with Fmoc-protected L-tryptophane 2 to form bis-ester 3. The resulting polymer-supported amino ester 3 was deprotected, and amino ester 4 underwent Pictet-Spengler reaction with varoius ketones to form tricyclic indoles 5. The nucleophilic piperidine in the tricyclic indole reacted with isocyanate to generate the urea intermediates and simultaneously intramolecular cyclization to release the target compounds 7 from the support in good yields.