title: Asymmetric α-hydroxylation of a lactone with vinylogous pyridone by using a guanidine-urea bifunctional organocatalyst: catalytic enantioselective synthesis of a key intermediate for (20S)-camptothecin analogues.
abstract: We have developed a catalytic asymmetric synthesis of (S)-4-ethyl-6,6-(ethylenedioxy)-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine-3,10(4H)dione (5 a), a synthetic intermediate for (20S)-camptothecin analogues. A key step in this synthesis is an asymmetric α-hydroxylation of a lactone with a vinylogous pyridone structure (8 a) by using a guanidine-urea bifunctional organocatalyst. The present oxidation was successfully applied to the synthesis of C20-modified derivatives of (+)-C20-desethylbenzylcamptothecin (13).
authors.affiliation: Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588 (Japan), Fax: (+81) 42-388-7295.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Watanabe
authors.forename: Minami
authors.initials: M
authors.lastname: Odagi
authors.forename: Kota
authors.initials: K
authors.lastname: Furukori
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nagasawa
mesh_terms: D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D006146:Guanidines; D006900:Hydroxylation; D007212:Indolizines / Q000737:chemistry*; D007783:Lactones / Q000737:chemistry*; D010084:Oxidation-Reduction; D011728:Pyridones / Q000737:chemistry*; D011753:Pyrones / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives
chemical_list: C000589857:(S)-4-ethyl-6,6-(ethylenedioxy)-7,8-dihydro-4-hydroxy-1H-pyrano(3,4-f)indolizine-3,10(4H)dione; D006146:Guanidines; D007212:Indolizines; D007783:Lactones; D011728:Pyridones; D011753:Pyrones; D014508:Urea; D002166:Camptothecin
keywords: camptothecin; guanidine; natural products; organocatalysis; urea