Chiral Technologies: Asymmetric Synthesis

Novasep Synthesis has a leading position in process development and production of chiral APIs via chiral chemistry. We owe this prevalence to the following assets:

• We have two sites at Finorga (Chasse-sur-Rhône and Mourenx)
• We master conventional chemistry and innovative technologies
• We handle chiral technologies such as
  • resolutions
  • asymmetric synthesis
  • chiral synthons
  • continuous chromatographic separation
    • SMB and Varicol®
    • from grams to 100's kg of pure enantiomer per day

Asymmetric synthesis is often seen as the route of choice by organic chemists. It consists of creating a chiral centre from an achiral molecule. The creation of this asymmetric centre is made possible using a chiral catalyst or a chiral auxiliary that will be bound covalently or not to the pro-chiral molecule.

Novasep masters and offers conventional resolutions and can combine them to innovative technologies such as preparative chromatography to obtain chiral molecules.

Classical Resolutions

a. Dynamic Resolution What would be a perfect resolution? It would be when one of the two isomers is removed, the wrong one is racemised in situ, resulting in larger proportions of the correct isomer. Such separations, named dynamic resolutions, are often the most cost-effective way of creating a pure chiral molecule from a racemic mixture.

b. Salt Resolution Achiral synthesis is often considered as faster and cost efficient compared to chiral synthesis. However the resolution step can be time-consuming and difficult. The most classical option for the resolution remains selective crystallization. Diastereoisomers resolutions involving chiral acids or bases are very frequent. Groupe Novasep has optimized such methods in combination with chromatography.

Stereo-enantio-specific Reactions

Complex APIs are often stereochemically demanding: the use of modern synthetic methods such as Transition Metal Catalysis (TMC) are key for cost effective and timely API manufacture with the advantage of direct synthesis of the desired enantiomer and the commercial availability of a broad range of catalyst systems.

Enzymatic Resolutions

Combining enzymatic resolutions and reverse substitutions can offer economic solutions. In the case described, Novasep Synthesis has developed a new synthetic route involving an enantioselective acetylation followed by a Mitsunobu reaction of the non reacted alcohol. Such approach has replaced a low-yield crystallization and resulted in significant savings.