Recently fluorination is one of an important strategy in medicinal chemistry, it sometime improves not only potency but also any ADMET profiles. Yes I like fluorination strategy ;)
However fluorination reaction is needed very harsh conditions. So I think fluorinated building blocks are very useful for medicinal chemistry to avoid such as harsh reaction steps in their synthetic routes.
Today I found interesting article published from ‘Enamine’ which is the one of big CRO in drug discovery area.
https://pubs.acs.org/doi/full/10.1021/acs.joc.9b00719
The group developed effective synthetic route of gem-difluorinated cyclobutan derivatives. In fig2 shows that only one article is found in Reaxys which describes gem-F cyclo-butane.
The author tried several route for the synthesis and key of the success was preventing enolization of cyclobutanone which is precursor of gem-F cyclobutane. (see Scheme2 in the article)
Finally they synthesized many type of gem-F cyclobutane derivatives in large scale.
In the experimental section, all reactions were conducted in gram scale!
The building blocks reported in the article have only one reaction point but it will be very useful BB for MedChem to control compound’s profiles.
Some years ago, I could have opportunity to visit Enamine. In the lab. was well organized and have high level science.
I would like to these BB if I could have my own drug discovery project near the feature.
