Biomimetic diversity-oriented synthesis of benzannulated medium rings via ring expansion Journal Article
| Authors: | Bauer, R. A.; Wenderski, T. A.; Tan, D. S. |
| Article Title: | Biomimetic diversity-oriented synthesis of benzannulated medium rings via ring expansion |
| Abstract: | Nature has exploited medium-sized 8- to 11-membered rings in a variety of natural products to address diverse and challenging biological targets. However, owing to the limitations of conventional cyclization-based approaches to medium-ring synthesis, these structures remain severely underrepresented in current probe and drug discovery efforts. To address this problem, we have established an alternative, biomimetic ring expansion approach to the diversity-oriented synthesis of medium-ring libraries. Oxidative dearomatization of bicyclic phenols affords polycyclic cyclohexadienones that undergo efficient ring expansion to form benzannulated medium-ring scaffolds found in natural products. The ring expansion reaction can be induced using three complementary reagents that avoid competing dienone-phenol rearrangements and is driven by rearomatization of a phenol ring adjacent to the scissile bond. Cheminformatic analysis of the resulting first-generation library confirms that these molecules occupy chemical space overlapping with medium-ring natural products and distinct from that of synthetic drugs and drug-like libraries. © 2013 Nature America, Inc. All rights reserved. |
| Journal Title: | Nature Chemical Biology |
| Volume: | 9 |
| Issue: | 1 |
| ISSN: | 1552-4450 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2013-01-01 |
| Start Page: | 21 |
| End Page: | 29 |
| Language: | English |
| DOI: | 10.1038/nchembio.1130 |
| PROVIDER: | scopus |
| PUBMED: | 23160003 |
| PMCID: | PMC3556477 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 2 January 2013" - "CODEN: NCBAB" - "Source: Scopus" - PMCID available 7/1/2013 |
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