In Ojima's early research career, he was mainly engaged in homogeneous catalysis of phosphine-Rh complexes, its development as new synthetic processes, as well as their applications to catalytic asymmetric synthesis and organic synthesis. He received a 25th CSJ Award for Young Investigator for his research on "Highly selective syntheses by means of organosilicon compounds – transition metal complex systems" from the Chemical Society of Japan in 1976. Through the 1970-1980s, he established himself as an authoritative scholar in catalytic asymmetric synthesis, editing a book, "Catalytic Asymmetric Synthesis" (Wiley-VCH) in 1993, and also published the second (2000) and third (2010) editions. This book collectively became a very popular reference book with >4,100 citations.[5] He has conducted research on the development of new synthetic methods based on transition-metal catalyzed reactions and investigations into their mechanisms, which includes hydrosilylation, silylformylation, silylcarbocyclizations (SiCaCs, SiCaB, SiCaT), higher order (carbonylative) cycloadditions, hydroformylation, hydrocarbonylations, amidocarbonylations, cyclohydrocarbonylations, and enantioselective processes such as hydrosilylation, hydrogenation, hydroformylation, Michael addition, allylic alkylation/amination/etherification, etc.[6]
Since the late 1970s, Ojima began his work in organofluorine chemistry by exploring the interface of fluorine chemistry and organometallic chemistry/catalysis. His research includes the development of processes for the highly regioselective hydroformylations of fluoro-olefins, synthesis of N-acylfluoroamino acids via hydroformylation-amidocarbonylation of fluoro-olefins, synthesis of a-trifluoromethylacrylic acid via carboxylation, novel ureidocarbonylation, synthesis of optically pure fluoroamino acids via enzymatic kinetic resolution, etc.[7] Ojima's synthesis of trifluoromethyluracil from 2-bromotrifluoropropene became an industrial process by Japan Halon (then, Tosoh F-Tech). Furthermore, this process was successfully applied to the commercial synthesis of trifluridine (trifluorothymidine), an antiherpes antiviral drug, primarily used on the eye topically, such as "Viroptic" by Tokyo Yuki Gosei Kogyo in early 1990s.[7] His work on optically pure fluoroamino acids and their use in medicinally active compounds, such as enkephalin, captopril and taxol (paclitaxel), brought medicinal and biomedical applications to the scope of fluorine chemistry community.[7] He edited a book, "Fluorine in Medicinal Chemistry and Chemical Biology" (Wiley-Blackwell, > 1,700 citations) in 2009, featuring the basic principles and exemplary applications of fluorine incorporation to biologically relevant compounds and systems.[8]
One of his achievements is the development of the "β-Lactam Synthon Method",[9][10] which has been applied to the synthesis of α- and β-amino acids, oligopeptides, peptidomimetics, taxanes and taxoids. This method has been successfully applied for the practical synthesis of the Ojima lactam, a key intermediate for the commercial production of paclitaxel (Taxol), one of the most widely used anticancer drug for chemotherapy, through the Ojima-Holton coupling,[11] as well as for the medicinal chemistry and development of new-generation taxoid anticancer agents.[11] One of his second-generation taxoids, "ortataxel", developed from 14-hydroxy-10-deacetylbaccatin III, and licensed to Indena, SpA, Italy, has advanced to the Phase II human clinical trials. The extensive SAR studies performed in his laboratory have led to the development of numerous highly potent novel second- and third-generation taxoids. The third-generation taxoids showed virtually no difference in potency against drug-resistant and drug-sensitive cell lines. Some of the next-generation taxoids also exhibited excellent potency against cancer stem cells. Other highlights include his common pharmacophore proposal for microtubule-stabilizing anticancer agents, identification of the paclitaxel binding site and its bioactive conformation in the β-tubulin based on photoaffinity labeling and computational analyses, identification of unique characteristics of the next-generation taxoids in cancer cell biology and their mechanism of action, and efficacious tumor-targeted drug delivery of highly potent next-generation taxoids.[11][12]
Currently, Ojima's research program is focused on the drug discovery and development of next-generation anticancer agents and their tumor-targeted drug delivery,[11][13] antibacterial agents,[14] antifungal agents,[15] and antinociceptive agents,[16] etc. In his research, all relevant chemistry and biological tools, including computer-aided drug design, chemical synthesis, computational biology, chemical biology and cell biology are integrated in close collaborations with structural biologists, computer biologists, cell biologists, oncologists, microbiologist, pharmacologists, anesthesiologists, toxicologists, etc.
As of January 2024, he has published >500 papers and reviews in leading journals, >100 issued patents, edited nine books, and given >135 plenary and invited lectures in international meetings. SciFinder lists >1,000 publications to his credit.
