title: Synthesis of (E)-oxindolylidene acetate using tandem palladium-catalyzed Heck and alkoxycarbonylation reactions.
abstract: Tandem reactions use consecutive reaction steps to efficiently synthesize compounds of high molecular complexity. This paper presents a tandem Pd-catalyzed Heck and alkoxycarbonylation reaction for the stereoselective synthesis of (E)-oxindolylidene acetates. The mechanism underlying the Pd-catalyzed tandem reaction involves the syn-carbopalladation of ynamides followed by alkoxycarbonylation with CO and alcohol. This method makes it possible to obtain the desired (E)-configuration of oxindolylidene acetates exclusively. We evaluated the scope of the reaction by applying optimal reaction conditions to the facile synthesis of a library of (E)-oxindolylidene acetates. The resulting (E)-oxindolylidene acetates exhibited potent anticancer activities against a variety of human cancer cell lines. The anticancer activities of some (E)-oxindolylidene acetates were even superior to those of known CDK inhibitors indirubin-3'-oxime and roscovitine.
authors.affiliation: National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 11221, Taiwan. wtli@nricm.edu.tw.
authors.forename: Wei-Jen
authors.initials: WJ
authors.lastname: Lin
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli 35053, Taiwan.
authors.forename: Kak-Shan
authors.initials: KS
authors.lastname: Shia
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli 35053, Taiwan.
authors.forename: Jen-Shin
authors.initials: JS
authors.lastname: Song
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli 35053, Taiwan.
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Wu
authors.affiliation: National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 11221, Taiwan. wtli@nricm.edu.tw.
authors.forename: Wen-Tai
authors.initials: WT
authors.lastname: Li
mesh_terms: D000438:Alcohols / Q000737:chemistry; D000577:Amides / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002248:Carbon Monoxide / Q000737:chemistry; D002384:Catalysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D000078183:Oxindoles; D010165:Palladium / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C000610865:(E)-oxindolylidene acetate; D000438:Alcohols; D000577:Amides; D000970:Antineoplastic Agents; D007211:Indoles; D009942:Organometallic Compounds; D000078183:Oxindoles; D047428:Protein Kinase Inhibitors; D010165:Palladium; D002248:Carbon Monoxide; D018844:Cyclin-Dependent Kinases