title: Total synthesis of hibarimicinone, a v-Src tyrosine kinase inhibitor possessing the pseudo-dimer structure of tetracycline.
abstract: The total synthesis of hibarimicinone, a potent v-Src tyrosine kinase inhibitor possessing thirteen stereogenic centers and an axial chirality, has been achieved. The key step to constructing the eight-ring skeleton was the double Michael–Dieckmann-type cyclization (Hauser annulation) using a thiolactone pseudo-dimer. These synthetic studies indicated the efficiency of the thiolactone-employed route to synthesize the multiply functionalized polycyclic compounds. The ABCD-ring moiety including the bridging ether was constructed by a strategy including oxidation of the C-ring hydroquinone and the subsequent transfer of the oxidation stage to the neighboring ring. The atropisomer of hibarimicinone was also synthesized to confirm the structure of the natural product.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Tatsuta
authors.forename: Seijiro
authors.initials: S
authors.lastname: Hosokawa
mesh_terms: D003500:Cyclization; D019281:Dimerization; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry; D006873:Hydroquinones / Q000737:chemistry; D009279:Naphthacenes / Q000138:chemical synthesis* / Q000737:chemistry; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry; D010084:Oxidation-Reduction; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013752:Tetracycline / Q000737:chemistry*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D006027:Glycosides; D006873:Hydroquinones; D009279:Naphthacenes; D009281:Naphthalenes; D047428:Protein Kinase Inhibitors; C456033:hibarimicinone; C007229:decalin; D019061:src-Family Kinases; D013752:Tetracycline; C031927:hydroquinone