Today I found very interesting article from researchers who is working at pfizer and Hitgen.
Pfizer and Hitgen launched drug discovery collaboration two years ago.
Hitgen is one of CRO with DNA-encoded library as core technology.
In the article the authors reported that they conducted photoredox reaction on DNA tag.
Photoredox reaction is very useful tool for medchem because it can perform C(sp3)-C(sp3) coupling in one step which is difficult to do with old traditional chemistry.
DeNA Encoded Library(DELI) is powerful method to generate large number of molecules however available reaction is limited for not DNA damaging reaction. So it is not suitable for DELI production which has harsh reaction conditions.
At first they optimized coupling reaction condition of decarboxylateve coupling between aryl-iodide and aliphatic carboxylic acid. Main side reaction is reductive de haloganation product. But they found good reaction condition and the condition can work very well.
Table 2 shows many examples of the coupling reaction with moderate ~ high yield. And table 3 shows that the reaction can apply for not only phenyl iodide but also hetero cycles. Such as pyridine, pyrimidine etc.
There are few examples at ortho position with moderate yield. Maybe it is steric effect.
Finally they showed example of parallel synthesis via LED Array.
Scheme3-c) shows 96 well prate type LED reactor. It is very beautiful ;)
To prevent oxygen exposure, they degassed and sealed the plate.
And also they tried different type of photoredox reaction such as desulfinative coupling, deborylative coupling adn cross electrophile coupling and all reaction progressed with moderate yield.
Optimized reaction conducted in DMSO/H2O media with room temperature.
Combination of new technology is always exciting isn’t it?