A Jocic-type approach for a practical and scalable synthesis of pyrrolonaphthoxazepine (PNOX)-based potent proapoptotic agents

Daniela Zisterer, Stefano Federico, Tuhina Khan, Nicola Relitti, Giulia Chemi, Margherita Brindisi, Simone Brogi, Ettore Novellino, Giuseppe Campiani, Sandra Gemma, Stefania Butini, 'A Jocic-type approach for a practical and scalable synthesis of pyrrolonaphthoxazepine (PNOX)-based potent proapoptotic agents', 2018, Tetrahedron Letters;

Abstract

We developed a Jocic-type protocol for the construction of the pyrrolonaphthoxazepine (PNOX) core. After an initial investigation based on the isolation of a trichloromethyl carbinol derivative, we shifted our attention towards a multicomponent single-step protocol. Screening of a variety of bases and solvents led to the identification of the optimum conditions for the preparation of the key a-aryloxy carboxylic acids to undergo intramolecular cyclization. The novel chemical route significantly improved overall yields for the preparation of PNOX-based compounds and was successfully extended to the preparation of 1,4-benzoxazinone-based templates.