Chiral scaffolds

This expertise is now being directed towards research into IP protected chiral scaffolds for the New Zealand biotech industry, for the development of chiral chemical libraries in-house.  

This follows a recent shift in the scientific methodology for the development of new pharmaceuticals to diversity oriented synthesis - a strategy for quick access to molecule libraries with an emphasis on skeletal diversity.  

Diverse chiral pyrrolidine scaffolds – often
available with protecting groups already in place.

The chiral scaffolds envisaged are functionally diverse iminosugars – whose synthesis IRL has world leading expertise in. 

Two pyrrolidine-containing, next-generation pharmaceuticals discovered by IRL are being developed under license by a US biotechnology company. 

Our expert team has deployed a range of synthetic approaches to a portfolio of chiral pyrrolidine scaffolds, most of which either leverage nature’s chiral pool or rely upon enzyme-mediated resolution technology. 

Pyrrolidines play critical roles as core structures in the design of drugs. The specific orientation of bioactive motifs in 3D space is pivotal in ligand-receptor and enzyme-inhibitor complexes, which are the underlying mechanism of action for many pharmaceuticals. 

When one enantiomer provides the efficacy of interest, the other enantiomer may be partially active or inactive, be an antagonist of the active enantiomer or have a different activity that could be desirable or undesirable. The scaffolds can be used in the development of pharmaceutical compound libraries, adding significant value to the drug discovery process through the introduction of structural complexity and diversity which could significantly increase lead identification hit rates. Of single-enantiomer approved drugs, 84 per cent contain multiple chiral centres. Our scaffolds offer up to three chiral centres. 

World-leading expertise 

Scientists from the Carbohydrate Chemistry group at IRL and the Albert Einstein College of Medicine in New York were the first in the world to propose a pyrrolidine-containing Purine Nucleoside Phosphorylase (PNP) inhibitor based on Transition-State theory. 

This collaboration led to the design of the now-patented immucillins – next-generation picomolar pharmaceutical inhibitors that lead to profound T cell-mediated immunosuppression.

The two pyrrolidine-based drug candidates of the immucillin class shown below have progressed to Phase II clinical trials in the treatments of T- and B-cell cancers and psoriasis.1, 5 Three more analogues are presently being evaluated for their potential to treat certain solid tumours and bacterial infections, and as antimalarials.6,7 

Chiral pyrrolidines for sale 

Our experience with structure optimisation to these ends has seen an intensification of interest and synthetic expertise in functionalised pyrrolidine chemistry in our laboratories. 

To leverage from this base, our team of innovative scientists at IRL is now making functionalised chiral pyrrolidine building blocks. This functionality enables, and follows, a recent shift to diversity-oriented syntheses which allow focused library approaches to drug discovery. 

We offer these building blocks for sale (www.glycosyn.com), enantiopure at the mg-to-g scale, and would also welcome customer requests for syntheses of more specific pyrrolidine motifs, which might be key structural components of natural bioactive molecules or other pharmacologically-interesting drug candidates. 

With access to over 40 PhD scientists, we invite you to contact our Business Development Manager below, to discuss our competitive pricing and premium quality fast-paced service for your company’s needs.