With our expertise in the development and production of pure enantiomers, we can identify and scale up the chiral technology that suits your molecule from early stage to commercial production. We have the facilities, the experience and the know-how to use the appropriate technology in our chiral toolbox to produce pure enantiomers. The key chiral technologies we master include:
- Asymmetric synthesis
- Chiral resolution by diastereomeric salt or complex formation
- Kinetic and Dynamic resolution
- Chiral chromatography
- Other solutions for chiral resolution
We have extensive experience in stereoselective synthesis using both diastereoselective and enantioselective synthesis at very large scale and our R&D scientists always keep themselves informed about the latest development in asymmetric synthesis, in order to identify the best synthetic route yielding pure enantiomers. The key stereoselective reactions we master include:
- Asymmetric catalysis including asymmetric organo-catalysis, enzymatic asymmetric synthesis and metal-catalyzed asymmetric synthesis
- Stoechiometric enantioselective synthesis
- Diastereoselective synthesis, including chiral auxiliary chemistry)
Our expertise and capacities in cryogenic reactions, biocatalysis, organometallic catalysis and hydrogenation are clearly very strong assets to successfully conducting stereoselective reactions.
Example of asymmetric synthesis using a chiral auxiliary:
Example of asymmetric synthesis using a chiral catalyst:
Chiral resolution by diastereomeric salt or complex formation
Resolution by diastereomeric salt or complex formation is probably the most common way to resolve racemic mixtures. It is based on the reaction of a racemate with an enantiomerically pure resolving agent.
This resolving agent can be an acid or a base if the racemate has a basic or acidic function, or a neutral resolving agent for neutral species that will lead to a complex formation. The goal is therefore to find a resolving agent that preferentially binds one of the enantiomers of the molecule to afford a species less soluble in the solvent media than the non-desired enantiomer. Thus the salt or complex that is formed can be separated, and converted back to the free acid, base, or neutral compound to lead to the pure desired enantiomer. The resolving agent can then be recycled.
A variation is to make a salt or a complex with the two enantiomers of the racemate, this will lead to the formation of two diastereomers with different physicochemical properties: one will be less soluble than the other in a solvent media, making the separation possible.
We always take diastereomeric salt or complex formation into account when screening the different possibilities offered by the chiral toolbox. However thanks to our extensive experience in chiral chromatography and our preparative chromatography capabilities, we have often experienced that chiral chromatography, with total solvent recycling as implemented by Novasep, is often much more interesting in terms of operating cost, time and robustness.
Kinetic and dynamic resolution
Kinetic Resolution (KR) occurs when the reaction, between a chiral agent (reagent, catalyst…) and a racemate, lead to a kinetic preference for one enantiomer over the other and therefore, lead to a resolution.
We mainly use kinetic resolution with symmetric prochiral starting material to form 100% of one enantiomer:
Dynamic Kinetic Resolution (DKR) is an improvement of kinetic resolution. In DKR, a racemization reaction takes place concurrently to the enantiomer formation, leading to the desired compound in 100% yield (Curtin-Hammet kinetics).
We have extensive experience in introducing dynamic kinetic resolution steps in order to obtain pure enantiomers in a cost-effective, scalable and elegant manner.
We combine our experience in designing and operating industrial chiral chromatography processes and technologies with our know-how in developing and scaling up challenging organic synthesis, to bring the more cost-efficient global chiral synthesis to reality.
We can rapidly develop an optimized process and use our own chromatography facilities to speed your product to market. Eventually, we can provide you with a versatile chromatography unit to install at your own site.
At early development stage, you need methods to rapidly and securely prepare grams to kilograms of your candidates, ready for the next clinical phase. For these reasons, we can use supercritical fluid chromatography systems with our Prochrom Supersep line. The SupersepTM technology is characterized by a high recycling rate of CO2, reducing production costs and making the process greener.
Learn more about the Supersep systems we produce.
From early to late development stage, we can provide an extensive range of high performance liquid chromatography systems (HPLC) with our Prochrom range. HPLC is the versatile chromatographic tools to perform chiral resolution with any racemic mixtures, even if they are highly polar or cytotoxic.
Learn more about the Prochrom systems we produce.
For late development and production, we propose the use of continuous chromatography Varicol® which is the more cost effective, robust and environmentally friendly route to produce your pure enantiomer at large-scale. Efficient and integrated solvent recycling translates into lower operational costs andreduces solvent consumption greatly.
Learn more about the Varicol® systems we produce.
Have a look to our purification capacities, including chiral resolution chromatography.
Other chiral resolution
We can also propose other options including enzymatic resolution, preferential crystallization and covalent diastereomers formation.