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DOI: 10.1055/a-2069-3913
Total Syntheses of 2,2′-Biindolyl Alkaloids via Cyanide-Catalyzed Imino-Stetter Reaction
This study was supported by the National Research Foundation of Korea (NRF) grants funded by the Korean Government (NRF-2021R1A2C1012984 and NRF-2021R1A5A6002803 (Center for New Directions in Organic Synthesis)).
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Abstract
2,2′-Biindolyl natural products have a long history of applications owing to their unique structural features and biological activities. In this Account, we describe the recent progress achieved by our research group in the total syntheses of several 2,2′-biindolyl natural products using the cyanide-catalyzed imino-Stetter reaction as the key reaction to construct the 2,2′-biindolyl scaffold from 2-aminocinnamic acid derivatives and indole-2-carboxaldehydes. The development of a novel protocol to access 2,2′-bisindole-3-acetic acid derivatives via the cyanide-catalyzed imino-Stetter reaction and its application to the total syntheses of class I (arcyriaflavin A), class II (iheyamines A and B), and class III (calothrixin B) 2,2′-biindolyl natural products are discussed.
1. Introduction
2. Synthesis of 2,2′-Biindolyl Compounds via Cyanide-Catalyzed Imino-Stetter Reaction
3. Total Synthesis of Arcyriaflavin A
4. Total Syntheses of Iheyamines A and B
5. Total Synthesis of Calothrixin B
6. Conclusion
Key words
2,2′-biindolyl alkaloids - cyanide catalyst - imino-Stetter reaction - structural diversity - total synthesisPublication History
Received: 06 March 2023
Accepted after revision: 05 April 2023
Accepted Manuscript online:
05 April 2023
Article published online:
11 May 2023
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For reviews, see:
In this Account, ‘the symmetry of 2,2′-biindolyl compounds’ was determined by the substituent pattern on each phenyl ring of the indole scaffold regardless of the substituent
For a proposed biosynthetic pathway of calothrixins A and B, see:
For selected examples, see:
For selected examples, see:
For selected examples, see:
2,2′-Biindolyl scaffold could be constructed via the base-catalyzed cyclization of oxalamides bearing o-toluidine derivatives. However, this protocol generally requires harsh reaction conditions, resulting in a limited substrate scope. For selected examples, see:
For selected examples of the construction of the 2,2′-biindolyl scaffold via Fisher indolization of 2-acetylindole derivatives and aryl hydrazines, see:
For the seminal report on the cyanide-catalyzed imino-Stetter reaction, see:
For selected examples of the application of the imino-Stetter reaction to the total synthesis of natural products, see:
For the selected examples of the Wacker oxidation, see:
For the previous examples of asymmetric decarboxylative allylic alkylation for the synthesis of tertiary α-carbonyl compounds, see: