[Development of novel synthetic organic reactions: synthesis of antitumor natural products and leading compounds for new pharmaceuticals].
Biologically active natural products with unique, highly complex molecular skeletons have been used as leading compounds for raw materials of new drugs. Due to the limitations of natural supply, highly efficient, large-scale syntheses and molecular design have been sought in drug discovery. For this purpose, we have focused on a synthetic strategy effective in developing novel reactions and reagents and found several useful regio- and stereospecific reactions, contributing to the synthesis of otherwise unattainable target molecules. The application of these reactions for the total synthesis of three types of potent cytotoxic natural products for the first time is described in this paper. The basic concept is first described. Then the total synthesis of anthracyclines, fredericamycin A, and discorhabdins is reported. Novel reactions using hypervalent iodine reagents under environmentally benign conditions are also described. The future prospects for this method are discussed.
Kita
Yasuyuki
Y
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan. kita@phs.osaka-u.ac.jp
D018943:Anthracyclines / Q000138:chemical synthesis*; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis*; D002625:Chemistry, Organic; D015195:Drug Design; D007546:Isoquinolines / Q000138:chemical synthesis*; D055601:Organic Chemistry Phenomena; D011809:Quinones / Q000138:chemical synthesis*; D013141:Spiro Compounds / Q000138:chemical synthesis*
D018943:Anthracyclines; D000972:Antineoplastic Agents, Phytogenic; D007546:Isoquinolines; D011809:Quinones; D013141:Spiro Compounds; C016660:fredericamycin A