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: Wei-Jen Lin, Kak-Shan Shia, Jen-Shin Song, Ming-Hsien Wu, Wen-Tai Li
• Journal: Organic & biomolecular chemistry (Org Biomol Chem) Vol. 14 Issue 1 Pg. 220-8 (Jan 07 2016) ISSN: 1477-0539 [Electronic] England
• PMID: 26552357 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• (E)-oxindolylidene acetate
• Alcohols
• Amides
• Antineoplastic Agents
• Indoles
• Organometallic Compounds
• Oxindoles
• Protein Kinase Inhibitors
• Palladium
• Carbon Monoxide
• Cyclin-Dependent Kinases

Topics

• Alcohols (chemistry)
• Amides (chemistry)
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Carbon Monoxide (chemistry)
• Catalysis
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cyclin-Dependent Kinases (antagonists & inhibitors)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Humans
• Indoles (chemical synthesis, chemistry, pharmacology)
• Molecular Structure
• Organometallic Compounds (chemistry)
• Oxindoles
• Palladium (chemistry)
• Protein Kinase Inhibitors (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship