Syntheses of aminoalcohol-derived macrocycles leading to a small-molecule binder to and inhibitor of Sonic Hedgehog

…, BZ Stanton, N Maloof, X Wang, SL Schreiber

Index: Peng, Lee F.; Stanton, Benjamin Z.; Maloof, Nicole; Wang, Xiang; Schreiber, Stuart L. Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 22 p. 6319 - 6325

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Citation Number: 52

Abstract

We report the synthesis and biological activity of a library of aminoalcohol-derived macrocycles from which robotnikinin (17), a binder to and inhibitor of Sonic Hedgehog, was derived. Using an asymmetric alkylation to set a key stereocenter and an RCM reaction to close the macrocycle, we were able to synthesize compounds for testing. High-throughput screening via small-molecule microarray (SMM) technology led to the discovery of a ...