Research
· Design and synthesis of target-oriented 11C- or 18F-labeled PET probes
PET imaging is a useful technique to elucidate the molecular mechanisms of bioactive compounds and their target biomolecules. 11C- and 18F-labeled compounds are widely used as probes in this method. These probes require, however, careful design of the synthetic route wherein the incorporation of the positron emitting nuclide must be carried out at the final or late stage of the synthesis due to their short lifetime (t1/2 for 11C = 20.4 min, 18F = 110 min). If 11C- or 18F-nuclide has to be additionally introduced to the structure of the original bioactive compound of interest, the modifiable position should be carefully assessed not to diminish the bioactivity. In any case, the synthetic route of the probe is frequently forced to change into the new one from that of the original bioactive compound. Furthermore, it sometimes needs to improve the bioactivity of the original compound to obtain reliable data. These problems are specific for PET chemistry and the difficulty depends on each project. Based on rational design of the probe and synthetic route, we are trying to develop practical 11C- and 18F-labeled PET probes to achieve clear analysis of the target biomolecules, which are necessary for smooth promotion of the projects collaborating with many researchers.
“Efficient syntheses of [11C]zidovudine and its analogs by convenient one-pot palladium(0)–copper(I) co-mediated rapid C-[11C]methylation”
Zhouen Zhang*, Hisashi Doi, Hiroko Koyama, Yasuyoshi Watanabe and Masaaki Suzuki*
J. Labelled Compd. Radiopharm. 2014, 57, 540–549.
· Development of novel strategies for efficient PET probe synthesis
For PET studies, not only the labeling method but also rational design of labeling precursors is crucial. However, paucity of a general method for preparing the precursors, which are usually supplied by cumbersome total syntheses that are usually achieved by a newly established synthetic route different from that of the original non-radioactive compound, impedes efficient development of PET probes. We have considered that the most straightforward way to address this issue is to prepare them directly from the corresponding non-labeled original compounds that are generally easily available. We have named this novel synthetic approach of PET probes as “molecular renovation strategy” and are making extensive efforts to realize this idea through the development of new reactions catalyzed by various transition metals.
“Ni/Cu-Catalyzed Defluoroborylation of Fluoroarenes for Diverse C–F Bond Functionalization”
Takashi Niwa*, Hidenori Ochiai, Yasuyoshi Watanabe, and Takamitsu Hosoya*
J. Am. Chem. Soc. 2015, 137, 14313–14318.
· Development of chemical tools and methods for chemical modifications
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Chemical modification of biomolecules provides functional biomolecules that are useful in various biological researches. Modification of antibody with 64Cu-chelated compound enabling PET imaging of biological drugs and candidates is a good example. However, site-specific chemical modification is still not easy. We are trying to develop practical methods for chemical modification of biomolecules based on the use of bioorthogonal groups.
· Development of new efficient synthetic methods of valuable compounds
We are also developing new synthetic methods to obtain variety of compounds that are anticipated to show bioactivity or applicable to biological researches. This includes the development of new catalytic system and new bond forming reactions.
“Generation of Arynes via Ate Complexes of Arylboronic Esters with an ortho-Leaving Group”
Y. Sumida, T. Kato, and T. Hosoya*
Org. Lett. 2013, 15, 2806–2809.
