Convergent synthesis and discovery of a natural product-inspired paralog-selective Hsp90 inhibitor
| Autor: | Todd Macklin, Philip LoGrasso, Valer Jeso, Glenn C. Micalizio, Subhas Chandra Pan, Lisa Cherry |
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| Rok vydání: | 2011 |
| Předmět: |
Biological Products
Natural product Molecular Structure Stereochemistry Ansamycin Lactams Macrocyclic Organic Chemistry Convergent synthesis Stereoisomerism Geldanamycin Biochemistry Benzoquinone Hsp90 inhibitor Quinone chemistry.chemical_compound Structure-Activity Relationship chemistry Dihydroxylation Benzoquinones HSP90 Heat-Shock Proteins Physical and Theoretical Chemistry |
| Zdroj: | Organic letters. 13(19) |
| ISSN: | 1523-7052 |
| Popis: | A convergent synthesis of benzoquinone ansamycin analogs is described that proceeds by a sequence of metallacycle-mediated alkyne–alkyne coupling, followed by site- and stereoselective dihydroxylation and global carbamate formation. These studies have led to (1) validation of alkyne–alkyne coupling to produce geldanamycin analogs that lack the problematic quinone, (2) the discovery that C6–C7 bis-carbamate functionality is compatible with Hsp90 inhibition, and (3) the identification of 1 as a nonquinone geldanamycin-inspired paralog-selective Hsp90 inhibitor. |
| Databáze: | OpenAIRE |
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