Background

As the most common organic cation, quaternary ammonium-based compounds are used daily within industrial, pharmaceutical, biological, and civilian contexts as surfactants, poragens, catalysts, agrochemicals, cosmetics, antimicrobials and pharmaceuticals. Ammonium species are the last configurationally stable chiral heteroatom to have a routine resolution/asymmetric route. To date, no enantioselective synthetic process for the construction of chirality at nitrogen with predictable enrichment is known.

Control of molecular chirality is a fundamental challenge in organic synthesis. Whilst methods to enantioselectively construct carbon-based stereocentres are well established, routes to enriched nitrogen stereocentres have proven more elusive. There is an unmet need for a synthetic method to generate enantiomerically enriched tertiary or quaternary ammonium salts from tertiary amines that are chiral due to a nitrogen stereocentre.

Technology Overview

Scientists at Durham University have successfully demonstrated that control of nitrogen-based chirality is easily achieved through a supramolecular recognition process. Chiral ammonium cations can be produced in excellent yields and selectivities. Given the vast applications of ammonium cations in society, access to this unique form of chirality allows interrogation of the fundamental importance of this chiral centre in molecules that shape our daily lives. As such, this Durham-based process is the only method available for the construction of nitrogen stereocentres, giving unique access to libraries of compounds previously inaccessible in useful synthetic quantities. Reliable access to these compounds offers the possibility to exploit this new form of chirality in previously unexamined settings.

Further Details

The work to date is summarised in the Nature paper: https://doi.org/10.1038/s41586-021-03735-5

Stage of development

A wide range of tertiary amines can be converted to chiral ammonium cations with common alkylating agents (e.g. Benzyl bromide, Benzyl iodide, allyl bromide, etc.). We are continually adding to the diverse library of amines competent in this process.

Benefits

Novel chemistry to reliably synthesise chiral ammonium cations
Potential to unlock new chiral products and processes
Excellent yields
Excellent selectivity
Inherently Scalable
Highly efficient material throughput
Potential to extend IP protection of chiral ammonium high value ammonium cations

Applications

Pharmaceuticals
Surfactants
Antimicrobials
Organo-catalysts
Agrochemicals
Cosmetics
Chiral Shift Reagents
Salt Resolution
Organic Structure Directing agents (OSDA) for chiral zeolite formation

Opportunity

Durham University is seeking expressions of interest from suitably positioned industry partners to take forward the commercial development of this novel and exciting synthetic route into industrially relevant processes and materials. We are particularly interested in those seeking to develop new chiral ammonium cations, and those wishing to extend the IP protection of chiral ammonium cation drugs (e.g. Buscopan, Relistor, Atrovent, etc.)

Chiral Ammonium

Patents

IP Status

Seeking