A Route to Lipid ALC-0315: a Key Component of a COVID-19 mRNA Vaccine

Saadati, Cammarone, Ciufolini 2022

Co-authored by NTx scientists Drs. Fariba Saadati & Marco Ciufolini.

Abstract

This paper describes a synthesis of ALC-0315 by a sequence that more than doubles the overall yield relative to the published one, and that employs much cleaner reactions, thereby facilitating purifications to a considerable extent

ALC-0315 is a key component of the Pfizer-BioNTech COVID-19 vaccine and a highly sought-after lipid for nucleic acid therapeutics research.

This paper, a study in reductive amination, describes a synthetic route that more than doubles the overall yield relative to the published one.

Key aspects of the work include the use of (i) a protected form of a poorly organic-soluble aminoalcohol, (ii) a TEMPO/bleach oxidation to produce crucial aldehydes, and (iii) a more organic-soluble triacyloxyborohydride reagent.