parallel synthesis of peptide-like macrocycles containing imidazole-4,5-dicarboxylic acid包含imidazole-4平行合成peptide-like重点,5-dicarboxylic酸.pdf

Molecules 2012, 17, 5346-5362; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Parallel Synthesis of Peptide-Like Macrocycles Containing Imidazole-4,5-dicarboxylic Acid Zhigang Xu 1, Kraig A. Wheeler 2 and Paul W. Baures 3,* 1 Department of Pharmacology and Toxicology, The University of Arizona, Tucson, AZ 85724, USA; E-Mail: zxu@ 2 Department of Chemistry, Eastern Illinois University, Charlestown, IL 61920, USA; E-Mail: kawheeler@ 3 Department of Chemistry, Keene State College, Keene, NH 03435, USA * Author to whom correspondence should be addressed; E-Mail: pbaures@; Tel.: +1-603-358-2769; Fax: +1-603-358-2525. Received: 5 April 2012; in revised form: 26 April 2012 / Accepted: 3 May 2012 / Published: 8 May 2012 Abstract: We prepared a series of peptide-like 14-membered macrocycles containing an imidazole-4,5-dicarboxylic acid scaffold by using known coupling reagents and protecting group strategies. Yields of the purified macrocycles were poor on average, yet seemingly independent of amino acid substitution or stereochemistry. The macrocycles retain some level of conformational variability as observed by both molecular modeling and X-ray crystallography. These macrocycles represent a new class of structures for further development and for future application in high-throughput screening against a variety of biological targets. Keywords: macrocycle; scaffold; library synthesis; imidazole-4,5-dicarboxylic acid 1. Introduction Natural products contain a wide va