title: Synthesis of the biologically active natural product cyclodepsipeptides apratoxin A and its analogues.
abstract: This paper describes the synthetic studies conducted on a marine natural product, cyclodepsipeptide apratoxin A. Total synthesis of the oxazoline analogue of apratoxin A was achieved. The conversion of oxazoline to thioamide, as well as thioamide formation from a serine-derived compound, were both unsuccessful. However, thiazoline formation from a cysteine-derived compound led to the total synthesis of apratoxin A. An in vivo study on synthetic apratoxin A revealed that it has potent antitumor activity, but with significant toxicity. Solid-phase synthesis of apratoxin A was accomplished using a preformed thiazoline derivative as a coupling unit. This method was used to synthesize several azido-containing analogues as precursors of molecular probes, and these analogues exhibited potent biological activity.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Doi
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D047630:Depsipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D047630:Depsipeptides; D010080:Oxazoles; C442201:apratoxin A