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

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.

1,5‐Benzoxazepines as a unique and potent scaffold for activity drugs: A review

“…To investigate the anticancer properties, a series of compounds were designed to show better lipophilicity by introducing a polar group or atom into the basic structure. [30] The obtained data suggested a relevant therapeutic potential for the newly developed compounds 29a and 29b as effective anticancer agents displaying efficacy on multiple cancer cell lines.…”

A Synthetic Overview of Benzoxazines and Benzoxazepines as Anticancer Agents

“…These compounds are enabled to bind to the active site of microtubules, and targeting agents, thus interfering with the microtubule involved in a variety of cell processes in eukaryotes, for example, growth, proliferation, or autophagy. Among the compounds, 82 and 83 were found to have better lipophilicity due to incorporation of a polar group or atom into the basic structure [77] and a relevant therapeutic potential for effective anticancer agents that display efficacy on multiple cancer cell lines.…”