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Large Scale Purification of Glycosides for Alzheimer's Disease Therapy

08 June 2015

Process scale chemistry calls for the big guns. In this paper, Biotage® Flash 400 cartridges were used to purify large batches of mixture in a process for producing a drug candidate for Alzheimer's disease. 


Gamma-secretase modulators (GSMs) are promising compounds for Alzheimer's disease therapy, due to their selective lowering of amyloid-β42 levels in the brain. An international team of researchers and development chemists have identified the GSM SPI-1865 as a candidate for a potential novel therapeutic agent. 

As part of the synthetic pathway to obtain SPI-1865, they synthesized large quantities of two cycloartenol triterpenoid glycosides "... under an aggressive timeline" from roots of Actaea racemosa (known as black cohosh, a perennial herb containing many organic compounds with known biological activity). In doing so, no less than 147 kg of extract solution was purified by batch-wise purification using a Biotage® Flash 400L KP-Sil cartridge, installed on a Biotage® Flash 400 system. The fractions contained 11.44 kg of extracted product. 

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Ruichao Shen, Nathan O. Fuller, Gerd Osswald, Wesley F. Austin, Jed L. Hubbs, Dieter Haag, Janos Kovacs, Steffen P. Creaser, Mark A. Findeis, Jeffrey L. Ives, and Brian S. Bronk, 2014Multikilogram-Scale Production of Cycloartenol Triterpenoid Glycosides as Synthetic Intermediates for a γ-Secretase Modulator. Organic Process Research & Development 2014 18 (6), 676-682DOI: 10.1021/op5000732

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