Porphyrin Chemistry Expertise 

Many of the challenges CML are asked to confront relate to the translation of a research scale synthesis into a process appropriate to deliver clinical drug substance. Timelines are usually very aggressive, and CML uses all our experience to minimize risks whilst at the same time meeting all quality and regulatory requirements.

THE COMPLEXITY OF PORPHYRIN

The project was run by Dr. Frank Ludley, who has much experience in porphyrin systems, and was initiated in December 2008. Starting from a discovery synthesis which included multiple chromatographic separations and had been run on a scale of >1g, Frank was able to redesign the synthesis such that all chromatography was removed, along with several synthetic steps – reducing the overall synthesis to 7 steps.

The critical stage – and the first cGMP step – was the assembly of the porphyrin ring itself. Very careful control and high dilution are required, meaning that it was necessary to run the chemistry in 1000L scale to generate 1kg of the required product! Strong nerves are required.

Subsequent functionalisations and isolations were successfully completed in the kilo lab, avoiding exposure to light or metals – these systems will hang on to any metals present – before the final formation of the metallo-complex. Characterisations and analytical development were far from trivial, with extensive use of MALDI-TOF MS to confirm structures.

SPACE-FILLING MODEL OF PORPHYRIN

In such a challenging project, lasting only 6 months from initiation to completion, much work needs to be carried out in parallel: without good project management in place the risks of failure would be very high . . .

Thanks to Frank CML proved once again to be a reliable expert in the design and scale-up of such macrocyclic systems. We enjoy the challenge – ask us!

Back to Fall 2009 Newsletter

Dr. Frank Ludley