Available Technology
Late-stage fluorination of biomedically-active molecules
Technology:
Fluorination technology
Markets Addressed
Positron emission tomography (PET) is an important molecular imaging technology in clinical oncology. Drug developers also value PET as a tool for pharmacokinetic and pharmacodynamic evaluation at an early stage of drug development. Such non-invasive molecular imaging is especially valuable for the development of drugs acting on the central nervous system (CNS), because information about blood-brain barrier passage and distribution within the brain can otherwise be difficult to obtain in humans. 18F-aromatics are a common motif in radiotracers, but to date, only a limited range of reactions is available for their preparations, thus restricting the choice of PET tracers available for imaging. Given the 18F half-life of 109.7 min, the radiosynthesis, purification, and formulation of the 18F radiotracers must be done as quickly as possible. Therefore, a functional-group-tolerant fluorination reaction that introduces 18F radiolabels into complex biomedically relevant molecules at late stage would provide new promising PET tracers and improve the synthesis of many PET tracers employed today and thereby increase their usefulness.
Innovations and Advantages
Over the past two years, Prof. Tobias Ritter’s research group has developed four reactions for late-stage fluorination. The reaction conditions and functional group tolerance of the new fluorination technology are well-suited for the fluorination of complex molecules and offers the first technology for late-stage fluorine introduction into functionalized molecules.
In the development of new PET radiolabels, electrophilic fluorinating reagents are attractive because they have the potential for more diverse reaction chemistry than nucleophilic reagents. However, existing electrophilic fluorinating agents are unable to produce 18F radiotracers of specific activity high enough to allow routine uses of complex molecules as PET tracers in the clinic.
The Ritter group has developed a new electrophilic fluorination reagent for the radioisotope 18F, using a strategy involves the use of transition-metals that can access a chemical space not achievable with conventional methods. They have recently developed a novel reagent that exhibits the desired reactivity profile.
Additional Information
Intellectual Property Status: Patent(s) pending
Publications:
Furuya T, Ritter T. 2009. Fluorination of boronic acids mediated by silver(I) triflate. Org Lett. 11(13):2860-3.
Furuya T, Strom AE, Ritter T. 2009. Silver-Mediated Fluorination of Functionalized Aryl Stannanes. J. Am. Chem. Soc. 131 (5): 1662-3.
Furuya T, Ritter T. 2008. Carbon-fluorine reductive elimination from a high-valent palladium fluoride. J Am Chem Soc. 130(31):10060-1.
Furuya T, Kaiser HM, Ritter T. 2008. Palladium-mediated fluorination of arylboronic acids. Angew Chem Int Ed Engl. 47(32):5993-6.
Tweet
Inventor(s):
Ritter, Tobias
Categories:
For further information, please contact:
Vivian Berlin, Director of Business Development
(617) 496-0474
Reference Harvard Case #3578