McCague Scientific Consulting

Chiral Technology

The offering of McCague Scientific Consulting in Chiral Technology stems from 15 years experience in the chiral process technology field including experience in the use of chiral technology to access new templates for pharmaceutical discovery.

Fundamentally, a single enantiomer of a chiral compound might be accessed by one of three strategies:

  1. by making it from another compound that is already chiral (chiral-pool approach)
  2. by inducing asymmetry in a reaction that transforms an achiral compound into a chiral one (asymmetric synthesis)
  3. by separating out the required enantiomer from its racemic mixture (resolution)

However some of the more imaginative solutions combine the above elements.  For instance, an asymmetric synthesis technology might be used to install a second stereocentre into a molecule that is already chiral, where the existing stereochemistry is insufficient to give the required diastereocontrol alone or would give the incorrect diastereoisomer altogether.  A second approach is to combine a resolution with an in-situ racemisation of the substrate to effect a 'dynamic resolution'; such a process is as effective as an asymmetric synthesis in that all of the substrate can be converted into the required enantiomer of product.

With the expertise in McCague Scientific Consulting, recommendations can be made of which chiral technologies to pursue in order to access a particular chiral target.  Alternatively, in evaluating a chiral technology (e.g for whether to invest in its development) its applicability can be addressed by reference to a representative set of compounds (e.g. of FDA-approved drugs).

The following are the three areas of chiral technology believed most applicable to bulk manufacture and on which McCague Scientific Consulting can advise:

  1. Crystallisation resolution technology - see its own page on this site, this is a particularly strong area of emphasis of this business
  2. Bioresolution with enzymes
  3. Asymmetric chemocatalysis (for example asymmetric hydrogenation)

With regard to the catalytic technologies, consideration is made not just to the enantioselectivity, but also to factors that are critical in scale-up and process economics, for instance catalyst availability, catalyst utilisation and simplicity of process conditions.  Indeed, it is often possible to raise the stereopurity of initially-obtained material by recrystallization.  Furthermore, for a complete synthesis it is often that the chiral technology only plays a role in one reaction step, so it is necessary to consider the Organic Synthesis as a whole and the Route/ Process Design issues.

McCague Scientific Consulting