Total Synthesis of (−)‐Indoxamycins A and B

• Published in: Angewandte Chemie Vol. 131; no. 20; pp. 6731 - 6734
• Main Authors: Hu, Naifeng, Dong, Changming, Zhang, Cuifang, Liang, Guangxin
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 13.05.2019
• Subjects: Carbon; Carvone; Chemistry; Cycloaddition; Enantiomers; Indoxamycine; Natural products; Organic chemistry; Polyketide; Tandemreaktionen; Totalsynthese
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.201902043

The concise total syntheses of (−)‐indoxamycins A and B is reported. The chemistry features a seven‐step preparation of a highly congested [5.5.6] tricyclic advanced common intermediate from a readily available R‐carvone derivative. Key steps involve a Pauson–Khand reaction for the rapid construction of a basic scaffold bearing a quaternary carbon, a copper‐catalyzed Michael addition for the introduction of another adjacent all‐carbon quaternary stereocenter, and a tandem retro‐oxa‐Michael addition/1,2‐addition/oxa‐Michael addition for the installation of a trisubstituted olefin side chain. This synthetic strategy allows for easy access to both enantiomers of this family of natural products and their analogues from cost‐effective starting material through straightforward chemical transformations. Die Totalsynthese von (−)‐Indoxamycin A und B beinhaltet eine Pauson‐Khand‐Reaktion, eine Tandemreaktion aus Retro‐Oxa‐Michael‐Addition, 1,2‐Addition und Oxa‐Michael‐Addition und eine Mukaiyama‐Aldolreaktion. Somit lässt sich in sieben Schritten aus einem R‐Carvon‐Derivat ein gemeinsames tricyclisches Intermediat generieren, aus dem wiederum in sechs oder neun Schritten die Synthese von (−)‐Indoxamycin A und B erfolgt.