Biology‐Oriented Synthesis of a Withanolide‐Inspired Compound Collection Reveals Novel Modulators of Hedgehog Signaling1. (3rd March 2015)

• Record Type: Journal Article
• Authors: Švenda, Jakub; Sheremet, Michael; Kremer, Lea; Maier, Lukáš; Bauer, Jonathan O.; Strohmann, Carsten; Ziegler, Slava; Kumar, Kamal; Waldmann, Herbert
• Is Part Of: Angewandte Chemie. Volume 127:Number 19(2015)
• Page Start: 5688
• Page End: 5694
• Publication Date: 2015-03-03
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201500112
• Languages: English
• ISSNs: 0044-8249

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Biology‐oriented synthesis employs the structural information encoded in complex natural products to guide the synthesis of compound collections enriched in bioactivity. The <italic>trans</italic>‐hydrindane dehydro‐δ‐lactone motif defines the characteristic scaffold of the steroid‐like withanolides, a plant‐derived natural product class with a diverse pattern of bioactivity. A withanolide‐inspired compound collection was synthesized by making use of three key intermediates that contain this characteristic framework derivatized with different reactive functional groups. Biological evaluation of the compound collection in cell‐based assays that monitored biological signal‐transduction processes revealed a novel class of Hedgehog signaling inhibitors that target the protein Smoothened.</p> </abstract>