Concise and Practical Asymmetric Synthesis of a Challenging Atropisomeric HIV Integrase Inhibitor

• Published in: Angewandte Chemie Vol. 127; no. 24; pp. 7250 - 7254
• Main Authors: Fandrick, Keith R., Li, Wenjie, Zhang, Yongda, Tang, Wenjun, Gao, Joe, Rodriguez, Sonia, Patel, Nitinchandra D., Reeves, Diana C., Wu, Jiang-Ping, Sanyal, Sanjit, Gonnella, Nina, Qu, Bo, Haddad, Nizar, Lorenz, Jon C., Sidhu, Kanwar, Wang, June, Ma, Shengli, Grinberg, Nelu, Lee, Heewon, Tsantrizos, Youla, Poupart, Marc-André, Busacca, Carl A., Yee, Nathan K., Lu, Bruce Z., Senanayake, Chris H.
• Format: Journal Article
• Language: English; German
• Published: Weinheim WILEY-VCH Verlag 08.06.2015; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Acylation; Acylierungen; Asymmetrische Synthesen; Asymmetry; Chemistry; Economics; HIV; Inhibitors; Ligands; Phosphanliganden; Suzuki-Kupplung; Synthesis; tert-Butylierung
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.201501575

A practical and efficient synthesis of a complex chiral atropisomeric HIV integrase inhibitor has been accomplished. The combination of a copper‐catalyzed acylation along with the implementation of the BI‐DIME ligands for a ligand‐controlled Suzuki cross‐coupling and an unprecedented bis(trifluoromethane)sulfonamide‐catalyzed tert‐butylation renders the synthesis of this complex molecule robust, safe, and economical. Furthermore, the overall synthesis was conducted in an asymmetric and diastereoselective fashion with respect to the imbedded atropisomer. Atropselektiv: Eine effiziente asymmetrische Synthese eines atropisomeren HIV‐Inhibitors wurde entwickelt. Durch die Kombination einer Kupfer‐katalysierten Acylierung mit der Verwendung von BI‐DIME‐Liganden in einer ligandengesteuerten Suzuki‐Kupplung und einer Bis(trifluormethan)sulfonamid‐katalysierten tert‐Butylierung wird die Synthese dieser komplexen Verbindung robust, sicher und wirtschaftlich.