Regioselective synthesis of 3‐(1H‐indol‐3‐yl)‐5‐(1H‐indole‐3‐carbonyl)‐4‐hydroxyfuroic acids: route to hydroxyfuroic acid‐based insulin receptor activators |
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| Authors: | Shan‐Yen Chou Henry J Tsai |
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| Institution: | 1. Pharmaceutical R&D Program, Development Center for Biotechnology, Hsi‐Chih City 221, Taiwan;2. Taigen Biotechnology Co., Taipei 114, Taiwan;3. Department of Biological Science and Technology, China Medical University, Taichung City 404, Taiwan;4. Department of Health and Nutrition Biotechnology, Asia University, Taichung County 413, Taiwan |
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| Abstract: | A new class of insulin receptor activator with a hydroxyfuroic acid in place of a hydroxyquinone moiety is reported. The synthesis of 3‐(1H‐indol‐3‐yl)‐5‐(1H‐indole‐3‐carbonyl)‐4‐hydroxyfuroic acids ( 26 – 30 ) requires seven major steps. Key elements in the syntheses include (1) sequential preparation of two 4‐(N‐protected indole)‐3‐methoxy‐furoic 2,5‐dicarboxylic esters ( 4 and 6 ); (2) regioselective conversion of the furoic diacid 8 into its C‐5 methyl ester 10 with methyl chloroformate; and (3) acylation of 10 by a 7‐substituted indole under a mild condition. This study demonstrates a feasible route of synthesizing insulin receptor activators with a hydroxyfuroic acid scaffold. Among those hydroxyfuroic acid compounds, compound 28 demonstrates insulin receptor activation potential comparable to Merck's compound 2 with a dihydroxybenzoquinone scaffold. Drug Dev Res 72: 247–258, 2011. © 2010 Wiley‐Liss, Inc. |
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| Keywords: | insulin receptor activator regioselective synthesis hydroxyfuroic acid |
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