title: Total synthesis of resorcinol amide Hsp90 inhibitor AT13387.
abstract: The synthesis of C-5-substituted resorcinol amide AT13387, a known Hsp90 inhibitor currently in clinical trials, is reported without the use of phenolic protection in an overall yield of 13.4%. Biomimetic aromatization and Suzuki-Miyaura cross coupling approach were employed to synthesize the resorcinol and iso-indoline units, respectively, which were efficiently coupled using Grignard-mediated amidation.
authors.affiliation: Department of Chemistry, Imperial College, London SW7 2AZ, England.
authors.forename: Bhavesh H
authors.initials: BH
authors.lastname: Patel
authors.forename: Anthony G M
authors.initials: AG
authors.lastname: Barrett
mesh_terms: D000577:Amides / Q000737:chemistry*; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D054833:Isoindoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D012118:Resorcinols / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000577:Amides; D001549:Benzamides; D018841:HSP90 Heat-Shock Proteins; D054833:Isoindoles; D012118:Resorcinols; C552103:(2,4-dihydroxy-5-isopropylphenyl)-(5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydroisoindol-2-yl)methanone; C031389:resorcinol