Expanding the Chemical Space: Functionalized Ethynyl Oxazoles as Versatile Reagents for the Click Chemistry

03 September 2024, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

The limited availability of synthetic techniques and methods, coupled with the sensitivity of the oxazole ring, has restricted the use of ethynyl-substituted oxazoles in drug design, despite their potential advantages. In this study, we present our extensive experience in oxazole chemistry through a comprehensive analysis of the oxazole core’s tolerance to various reaction conditions for selective modifications. Additionally, we aimed to optimize synthetic protocols to develop efficient methods scalable to multigram quantities in a single run. We also sought to identify mild, tolerant approaches to address the instability of the oxazole ring and manage potential side reactions. Our work led to the development of an efficient approach for performing click reactions on ethynyl heterocycles, resulting in excellent yields and a straightforward purification process. This opens up a largely unexplored space for incorporating small molecule oxazoles into drug targets via click reactions with various azides. These findings could significantly advance oxazole chemistry and their integration into drug development programs.

Keywords

oxazoles
acetylenes
azides
click chemistry

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.