A Convenient Synthesis of Novel Isoxazolidine and Isoxazole Isoquinolinones Fused Hybrids

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2024 Jan 11

PMID 38202674

Authors

Konstantinos A Ouzounthanasis

Stergios R Rizos

Alexandros E Koumbis

Affiliations

Soon will be listed here.

Abstract

Isoxazolidine, isoxazole, and isoquinolinone rings are present in the structure of several natural products and/or pharmaceutically interesting compounds. In this work, facile and efficient pathways have been developed for the preparation of fused frameworks bearing those heterocycles. The successful approaches for both isoxazolidine/isoquinolinone and isoxazole/isoquinolinone hybrid syntheses relied initially on 1,3-dipolar cycloadditions of nitrones and nitrile oxides to indenone and 2-propargylbenzamide, respectively. The construction of the isoquinolinone lactam system followed by performing a selective Schmidt reaction for isoxazolidine derivatives (two steps overall), whereas the isoxazole lactams were reached via an Ullmann-type cyclisation (three steps overall). Key observations were made regarding the stereo- and regioselectivities of the reactions employed, and small libraries of the targeted hybrids were prepared, demonstrating the general applicability of these strategies.

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