This book is devoted to highly polished and potentiated novel C couplings developed by our group (M. Suzuki) in the course of a long-term, tight collaboration of chemistry, biology, and medicine experts, focusing on advanced organometallic techniques for the construction of a whole prostaglandin (PG) framework and new methodology for introducing short-lived 11C radionuclide into carbon frameworks. The book is written to attract the interest of scientists working in chemistry and interdisciplinary research areas such as medicinal chemistry, radiochemistry, chemical biology, molecular imaging, and related industries.Go to the book
General synthesis of prostaglandins (PGs) has been accomplished based on a one-pot three-component coupling using a combination of organocopper or organozincate conjugate addition to 4-hydroxy-2-cyclopentenone followed by trapping of resulting enolate with an organic halide. Based on the use of this synthetic methodology, biologically significant PG derivatives including ent-Δ7-PGA1, 15SAPNIC ([3H]APNIC), and 15R–TIC have also been synthesized. Ultimately, organozincate conjugate addition combined with the enolate trapping by an organic triflate results in practical green three-component coupling comprising the use of stoichiometric amounts of three components (enone, α- and ω-side chains in a nearly 1:1:1 ratio) without using HMPA and heavy metals. General methodology for introducing short-lived 11C and 18F radionuclides into carbon frameworks has been established by developing rapid C-[11C]methylation and C-[18F]fluoromethylation using Pd0-mediated rapid cross-coupling between [11C]methyl iodide and an organotributylstannane or organoboronate; or [18F]fluoromethyl bromide and organoboronate, respectively, allowing the synthesis of a wide variety of biologically significant and disease-oriented PET probes such as 15R-[11C]TIC. Moreover, PdII-mediated rapid C-[11C]carbonylation using [11C]CO and organoboronate at ambient temperature under atmospheric pressure using conventional helium carrier gas has been explored. Further, C-[11C]carboxylation has been promoted using [11C]CO2 and organoboronate with RhI catalyst under atmospheric pressure.