Visible Light Photosynthesis: ‘Making Light Work’ of Pharmaceutical Manufacture
Joshua P. Barham,a,b Matthew P. John,a John A. Murphyb
aGSK
Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY
bDepartment of Pure & Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL
Visible light as an energy source to power chemistry
Aim: Harness light to synthesise pharmaceuticals
• Until now, industry has relied mainly on thermal energy to power chemistry
• ‘THIQ’ core prevalent in pharmaceuticals and natural products
• What if chemical reactions could be powered by visible light?
• A key challenge is incorporating fragments adjacent to the N atom
 Sustainable
 Abundant
 Safe
Visible Light
Advantages
 Practical
 Different chemistry
http://eetd.lbl.gov/newsletter/nl19/
• But most organic molecules do not absorb visible light…
• What can be learnt from Nature?
Visible light photosynthesis of medicines mimics nature
• Reaction diagnostics predicted the ‘THIQ’-core could be activated
Novel light-powered methodology developed
• ‘THIQ’ core activated to install fragments adjacent to the N atom
http://sciencerocksuk.co.uk/photosynthesis/
• Nature’s approach: sunlight-powered chlorophyll for photosynthesis of sugar
 Rapid (1 hour)
 Sustainable
 Safe
 Wide scope (28 examples)
 Efficient (up to 95% product yields)
• Versidyne® was synthesised for the first time using light
http://cen.acs.org/articles/93/i40/Celebrating-International-Year-Light.html
• Proposed approach: visible light-powered catalysts to photosynthesise medicines
Combining technologies to enhance productivity
How does it work?
• ‘Flow chemistry’: chemical reactions run in a continuously flowing stream
• Catalyst activated by absorbing visible light
• Benefits: high surface area, excellent mixing, consistent product purity
• Competing pathways: activated catalyst undergoes chemistry or emits light
**good light penetration**
LEDs
PTFE
tubing
• Chemistry deactivates the catalyst, in turn this activates the starting chemical
• Once the starting chemical is activated, it reacts to give the product
Diagnostics developed allow the prediction of success
• When chemistry is occurring, light emission decreases
Emission: catalyst + chemical Y
Emission Intensity
Emission Intensity
Emission: catalyst + chemical X
Catalyst only
Catalyst + chemical
• ‘Flow chemistry’ gave a >3000% increase in productivity!
BATCH
0.2 grams / hour = 34 grams / week
FLOW
6.7 grams / hour = 1 kilo / week
Conclusions
• 28 biologically active compounds photosynthesised using visible light
Blue
Red
chemical X
‘THIQ’ core
Blue
Red
• Diagnostics allowed predictions which saved development time by >90%
• ‘Flow chemistry’ successfully enhanced productivity by >3000%
chemical Y
• Publication in a peer-reviewed journal