14C Radiosynthesis; Diels Alder Solutions to Challenging Syntheses
Posted on Mon, Nov 14, 2011 @ 05:57 AM
International Isotope Society; 26th Northeast US Chapter Symposium
The 26th International Isotope Society Northeast US Chapter Symposium took place on October 27th 2011 in Morristown NJ.
Around 100 people participated, representing a spectrum of US and European pharmaceutical companies and suppliers of isotopically labelled compounds. Nine lectures and ten posters were presented, covering synthetic methods and the use of labelled compounds in drug development.
The overall, take-home message, from the conference was that isotope labelling was still an absolutely essential tool for the Pharmaceutical Industry, giving rapid and quantitative data that allowed for timely and informed decision making.
Carbon-14 Radiosynthesis; Applications of Diels Alder Reactions
At the meeting, Jon Bloom, Quotations Manager at Quotient Bioresearch, gave a presentation entitled "Three Applications of the Diels Alder Reaction in Carbon-14 Radiosynthesis".
The Diels Alder Reaction is well known to organic chemists; it is the cycloaddition of a diene with an electron deficient alkene to give a cyclohexene. It is however very rarely used in radiosynthesis, so the presentation was well attended.
Jon gave details of three difficult syntheses, and how chemists at Quotient used Diels Alder Reactions to provide customers with the required end product.
The three products synthesised were: 
1) [14C]Nortilidine
[14C]Nortilidine was required by our client and is made inactively in industry by use of the Diels Alder reaction to form the cyclohexene ring. The radiosynthesis by the same route proved challenging. Our chemists modified the Diels Alder step to deliver the target, [14C]Nortilidine.
2) [14C]Acrolein
In this case, we demonstrate how [14C]Acrolein can be prepared in small samples for synthesis or other studies on demand from a stable intermediate that can be readily stored, subdivided and purified.
3) [14C]Frenolicin B
This is made using a Diels Alder reaction using trimethylsiloxy-[14C]butadiene and a quinone. It gave a surprise by-product which fortunately could be removed by HPLC.
Each synthesis posed interesting challenges, not least the storage of a stable intermediate.
A combination of literature research, knowledge based on years of experience, and dedication to customer satisfaction resulted in three successful syntheses.
Download the presentation now for the full story.
