Synthetic methodology program at MCCB

Innovations in the synthetic methodology has been one of the key drivers in organic chemistry research for decades. In the academic persepective, discovery of new synthetic methods often parallels with the finding of new chemical reactivity associated with various functional groups, which can makes advancement in our understanding on chemistry itself. Furthermore, new synthetic methods can be also applied to a plethora of industrial production processes. In particular, a recent surge of efficient catalytic methods  is transforming the conventional chemical processes to become more green and carbon-neutral. In that sense, the synthetic methodology program at MCCB has two main goals; First, to nurture the students to better understand the chemistry behind organic synthesis. Second, to streamline the synthetic procedures for preparation of complex bioactive molecules, preferrably by employing effective catalytic systems. 

Peptides are important chemical entities exhibiting biological activities. Preparation of peptide molecules involves solid-phase synthesis in which the amino acid building blocks are added sequentially on the reaction nucleus anchored on the solid support. This process innovated by a Nobel laureate, R. Bruce Merrifield, is called solid-phase peptide synthesis (SPPS), and it is considered as the standard method for peptide synthesis. 

In an effort to optimize the biological activity of a peptide molecule, one would need a variety of different amino acid building blocks. Unfortunately, however, unnatural amino acids useful for activity tuning are commonly very expensive and hard to synthesize. In that regard, we devised a new approach to synthesize various aryl group-containing amino acid building blocks directly applicable to SPPS based on the C–H functionalization. The cross-coupling reaction literatally revolutionized the industrial synthetic processes, and such a large impact has led to the endowment of Nobel prize to the early innovators including Akira Suzuki, Richard Heck, and Ei-ichi Negishi. Without a doubt, the contributions of these giants are enormous, but their early designs have limitations in that the implementation of reactive functional groups such as boron and zinc is necessary. By contrast, recent advancements have revealed that simple C–H bonds can be selectively activated for further elaboration including cross-coupling reactions. In consideration of such simplicity as well as atom- and step-economical nature, we decided to attempt the application of the C–H activation chemistry to functionalize various amino acid building blocks. 

Edited in Feb, 2023.