A Diamino Alcohol Catalyzed Enantioselective Crossed Aldol Reaction of Acetaldehyde with Isatins – A Concise Total Synthesis of Antitumor Agents. Issue 26 (17th July 2017)

• Record Type: Journal Article
• Authors: Subba Reddy, Ummareddy Venkata; Chennapuram, Madhu; Seki, Kento; Seki, Chigusa; Anusha, Bheemreddy; Kwon, Eunsang; Okuyama, Yuko; Uwai, Koji; Tokiwa, Michio; Takeshita, Mitsuhiro; Nakano, Hiroto
• Is Part Of: European journal of organic chemistry. Issue 26(2017)
• Page Start: 3874
• Page End: 3885
• Publication Date: 2017-07-17
• Subjects: Amino alcohols -- Enantioselectivity -- Aldol reactions -- Organocatalysis -- Total synthesis; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201700399
• Languages: English
• ISSNs: 1434-193X

Abstract

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. Abstract : The catalytic activities of diamino alcohols as bilateral activation catalysts for the enantioselective crossed aldol reactions of isatin derivatives with acetaldehyde are evaluated. The 3‐alkyl‐3‐hydroxyindolin‐2‐one products are used for the total synthesis of the bioactive natural products phaitanthrin B, cephalanthrin A, chimonamidine, and donaxaridine as well as the formal synthesis of CPC‐1.