title: [Syntheses of biologically active natural products using metal-mediated reactions as key reactions].
abstract: This review deals with total syntheses of biologically active natural products by the use of metal-mediated coupling reactions as key steps. First, we explored the coupling reactions mediated by samarium (II) diiodide (SmI2), which is a useful versatile one electron reducing reagent. The SmI2-mediated coupling reactions of N,N-dibenzyl-alpha-bromoamide and N,N-bis(p-methoxyphenyl)-alpha-bromoamide with carbonyl compounds gave the corresponding beta-hydroxyamides, respectively. Then, oxidative treatment of compound 6c with ceric (IV) ammonium nitrate (CAN) gave d,l-myrmicacine (7b). Synthesis of pyrrolizidine alkaloid pyrrolam A (8), which causes damage to fertilized eggs at a low concentration, was accomplished via the SmI2-mediated cyclization between a bromoalkyl and ynamide group. Next, (+/-)-oxerine (15), a monoterpene alkaloid, was synthesized starting from 3-bromopyridine. The synthesis of (+/-)-oxerine (15) was also carried out via the SmI2-mediated intramolecular cyclization of gamma-ethynyl bromide (40). Next, we focused on the palladium-catalyzed oxidation of alcohol and tried to expand it to the intermolecular cyclization. As a result, treatment of hydroxy-enamines and hydroxy-amines with a palladium catalyst gave the corresponding pyrroles and indoles in moderate to good yields. Finally, the syntheses of three pyrrolidine alkaloids were described. The chromium (II) chloride-mediated coupling reactions of (R)- and (S)-Garner aldehydes (56 and 57) with allyl bromides proceeded with moderate stereoselectivity to afford the corresponding homoallyl alcohols, which were converted to (2R, 3S)-2-hydroxymethyl-3-hydroxypyrrolidine (61), (2R, 3R, 4R)-3-hydroxy-4-methylproline (66), and the enantiomer (77) of (-)-bulgecinine (78).
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Aoyagi
authors.forename: A
authors.initials: A
authors.lastname: Ohta
mesh_terms: D017605:Bromine Compounds; D002384:Catalysis; D002712:Chlorides; D017608:Chromium Compounds; D003500:Cyclization; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis; D007454:Iodides; D010084:Oxidation-Reduction; D010165:Palladium; D011758:Pyrroles / Q000138:chemical synthesis; D011759:Pyrrolidines / Q000138:chemical synthesis*; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis*; D012493:Samarium
chemical_list: D017605:Bromine Compounds; D002712:Chlorides; D017608:Chromium Compounds; D007202:Indicators and Reagents; D007211:Indoles; D007454:Iodides; D011758:Pyrroles; D011759:Pyrrolidines; D011763:Pyrrolizidine Alkaloids; C419422:pyrrolam A; D012493:Samarium; D010165:Palladium; C017133:chromous chloride; C409809:samarium diiodide