The development of continuous flow processes for the manufacture of chemical entities in addition to offering advantages over batch chemistry also affords the researcher the opportunity to to perform inline downstream processing and purification often facilitated through the use of of solid supported reagents and scavengers. The development of solid supported catalysts is of particular interest as it affords the means to perform reactions with precise control to catalyst exposure and it potentially negates the need for further purification steps to remove spent catalyst from the reaction mixture. Ian’s research focuses on the development of flow based routes to pharmaceuticals with an emphasis on the incorporation of heterogeneous catalyst systems.
2. Landscape and opportunities for active pharmaceutical ingredient manufacturing in developing African economies
D.L. Riley, I. Strydom, R. Chikwamba and J.-L. Panayides, Reaction Chemistry and Engineering 2019, 4, 457-489
Africa is one of the world’s fastest growing economies, with South Africa having the fifth highest worldwide pharmaceutical expenditure per capita. In recent years, several companies have considered regional pharmaceutical production but have failed to make the investment, in stark contrast to the massive growth in pharmaceutical production in other BRICS countries. Major constraints identified have been the small local market, lack of skills, and an export-averse culture, which have prevented regional manufacturers from achieving the economies of scale that are essential to survive in a global market. In contrast, the pharmaceutical industry is undergoing a revolutionary change in manufacturing, with the potential to switch from batch manufacturing to continuous flow processing. The possibility of applying this new pharmaceutical business model in emerging markets will open the door for dramatic changes in regional commercial manufacturing. Advances in cloud computing, automation and system unification are paving the way for continuous active pharmaceutical ingredient production with integrated digital connectivity. This review will highlight the opportunities that exist in the localization of cutting-edge manufacturing technologies; in order to show the potential application of fundamental process research key production examples relevant to the region will be provided.
*2019 Emerging Investigators issue*
1. Immobilized tetrakis(triphenylphosphine)palladium(0) for Suzuki–Miyaura coupling reactions under flow conditions
G.V. Ramaotsoa, I. Strydom, J.-L. Panayides, D.L. Riley Reaction Chemistry and Engineering 2019, 4, 372-382
An immobilized triphenylphosphine scaffold was prepared by precipitation polymerization and functionalized to afford a cost-effective source of solid-supported tetrakis(triphenylphosphine)-palladium(0). The catalyst was characterised and used to perform biphasic Suzuki–Miyaura cross-coupling reactions using a packed-bed reactor under flow conditions. The approach afforded comparable yields to those obtained under batch conditions with a single pass through the packed-bed reactor (1 h vs. 18 h). The use of a recycling system was investigated on a model reaction and found to afford close to quantitative conversion within 3 hours.
*2019 Emerging Investigators issue*
- SelectBio Flow Chemistry Europe 2019, Cambridge, UK, February 2019: Supported ionic-liquid phase catalysis for the Suzuki-Miyaura reaction towards the synthesis of a clinical trial drug candidate, I. Strydom*, B. Deadman, K.K. Hii, J.-L. Panayides, D.L. Riley
- 2016 Frank Warren Conference, Rhodes, South Africa, December 2016: The stereoeselective continuous flow synthesis of Fluoxetine utilising formaldehyde gas, I. Strydom*, D.L. Riley