Extracting target compounds from large volumes of mixture confronts chemists with challenges which are right at the heart of large scale process chemistry. Ruichao Shen at Satori Pharmaceuticals knows exactly what it takes.
Figure 1: Root nodules of Actaea racemosa, a well known medicinal herb containing a candidate precursor for a novel Alzheimer remedy.
Ruichao Shen, Lead Scientist of Chemical Development at Satori Pharmaceuticals Inc. is a leading figure in the field of process chemistry with pedigee from Harvard and has written several books and publications on the topic. In 2014 he was the first author of a paper on large scale glycoside production, focusing on finding a drug candidate for Alzheimer’s disease.
“The problem we faced was to find an efficient method to purify the crude mixture as fast as possible and maintain a good recovery at the same time. At that time Biotage had the largest pre-packed silica cartridge available in the industry. We chose the product and it helped us solve the problem well.”
More often than seldom, the big guns are called for in Ruichao Shen’s line of work. Producing a small quantity of end product can require an enormous funnel entry, far beyond the scope of your average lab scale. In the case of the Alzheimer study, nearly 150 kg of root extract from Actaea racemosa was purified down to 11.44 kg of product using Biotage® Flash 400 cartridges.
“In the production of a key intermediate for synthesis of our preclinical candidate compound, we need to purify 50 kg of crude extract obtained from biomass. The crude was divided into 10 portions, and each portion was loaded on a preconditioned Biotage KP-Sil flash 400L silica gel column installed on Biotage Flash 400, and eluted with a gradient of 2−15% MeOH in DCM.”
With the stakes involved in large scale synthesis projects, reliability is everything, and all parts in the chain need to deliver.
“Biotage is one of the major providers of chromatography products. They have a good reputation.”
But production on this scale comes at a cost. The volume of mixture to be purified consumes silica like Re-using cartridges
“We used more than twenty 40 kg columns of silica in this project. That’s a lot of silica gel in total. It would be great to find an efficient way recycle the used silica – it is good for the environment and it also makes the chemists feel good when using them.”
Read more
Multikilogram-Scale Production of Cycloartenol Triterpenoid Glycosides as Synthetic Intermediates for a γ-Secretase Modulator, Org. Process Res. Dev., 2014, 18 (6), pp 676–682.
Figure 2: Biotage® Flash 400 is a flash purification system for large scale purifications.
Literature number: PPS397
