A Diamino Alcohol Catalyzed Enantioselective Crossed Aldol Reaction of Acetaldehyde with Isatins – A Concise Total Synthesis of Antitumor Agents

Ummareddy Venkata Subba Reddy, Madhu Chennapuram, Kento Seki, Chigusa Seki, Bheemreddy Anusha, Eunsang Kwon, Yuko Okuyama, Koji Uwai, Michio Tokiwa, Mitsuhiro Takeshita, Hiroto Nakano

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Abstract

Enantioselective crossed aldol reactions of isatin derivatives and acetaldehyde have been developed with a series of simple diamino alcohol catalysts to afford 3-substituted 3-hydroxyindolin-2-ones in high chemical yields (up to 95 %) and optical purities (up to 92 % ee). The synthetic potential of the present protocol has been demonstrated by concise, enantioselective, protecting-group-free, and transition metal-free total syntheses of antitumor and antiviral agents with the tryptanthrin architecture, that is, phaitanthrin B and cephalanthrin A, along with the biologically active indolidine alkaloids chimonamidine and donaxaridine as well as the formal synthesis of CPC-1. The highly enantioselective outcome of this catalytic crossed aldol reaction was evaluated by calculating the Gibbs free energies of the possible transition states.

Original languageEnglish
Pages (from-to)3874-3885
Number of pages12
JournalEuropean Journal of Organic Chemistry
Volume2017
Issue number26
DOIs
Publication statusPublished - 2017 Jul 17

Keywords

  • Aldol reactions
  • Amino alcohols
  • Enantioselectivity
  • Organocatalysis
  • Total synthesis

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry

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    Subba Reddy, U. V., Chennapuram, M., Seki, K., Seki, C., Anusha, B., Kwon, E., Okuyama, Y., Uwai, K., Tokiwa, M., Takeshita, M., & Nakano, H. (2017). A Diamino Alcohol Catalyzed Enantioselective Crossed Aldol Reaction of Acetaldehyde with Isatins – A Concise Total Synthesis of Antitumor Agents. European Journal of Organic Chemistry, 2017(26), 3874-3885. https://doi.org/10.1002/ejoc.201700399