Claisen Self-Condensation of Lactones in the Synthesis of Ionizable Lipids

Nabi et al. 13 August 2024

Co-authored by NanoVation’s Ardalan Nabi, N. D. Prasad Atmuri, Deaglan Arnold, Fariba Saadati, Huy Tran, and Marco A. Ciufolini.

Abstract

The Claisen self-condensation of lactones can be carried out safely and efficiently under Mukaiyama conditions, in the presence of TiCl4 and triethylamine. The primary Claisen products can be elaborated to various derivatives or converted directly into dihydroxyketones. Such compounds are valuable educts for the synthesis of ionizable lipids for the delivery of nucleic acid therapeutics and can now be accessed through a concise, economical, scalable route that avoids more technically challenging reaction sequences.