Yulong An; Ke Li; Yanfang Shen; Zibing Hong; Linlin Chen; Yujing Hu; Lichun Zhou; Disha Wang; Xiaodong Shi; Shien Liu; Wenji Su; Weiren Cui; Letian Kuai; Hongfang Yang; Xuanjia Peng
Org. Lett., 2020, 22, 10, 3931-3935
https://doi.org/10.1021/acs.orglett.0c01215

Abstract

A robust DNA-compatible Wittig reaction mediated by PPh2CH3 has been validated for DNA-conjugated α-chloroacetamides with aldehydes and, alternatively, DNA-conjugated aldehydes with α-halo acetamides or ketones. Further, 2-aminopyridines were acylated with α-chloroacetyl chloride and then reacted with DNA-conjugated aldehydes. Lastly, a pilot library employing our optimized Wittig reaction protocol was synthesized. The ability to generate α,β-unsaturated carbonyl compounds may be particularly useful for the design of DNA-encoded libraries capable of covalently interacting with protein targets.