5) Photocatalytic and Chemoselective H/D Exchange at a-thio C(sp3)-H Bonds
R. Ogasahara,‡ M. Mae,‡ Y. Itabashi, K. Ohkubo, K. Matsuura, H. Shimizu, K. Ban, M. Togami, T. Udagawa, H. Fujioka, M. Kamiya, S. Akai, Y. Sawama*
‡ equally contributed
J. Am. Chem. Soc. 2025 just accepted.
Abstract: Deuterated compounds used in drug discovery and live-cell imaging have recently gained the attention of various scientific fields. Although hydrogen-deuterium (H/D) exchange reactions are straightforward deuteration methods, achieving perfect chemoselectivity is challenging. We report the highly chemoselective deuteration of a-thio C(sp3)-H bonds using a thioxanthone or anthraquinone organic photocatalyst bearing an aromatic ketone skeleton and D2O as an inexpensive deuterium source under 390 nm irradiation. Notably, deuterium incorporation at the a-positions of O/N atoms, benzylic positions, and aromatic rings was not observed. The present chemoselectivity was accomplished via a single electron transfer mechanism between the photocatalyst and S-containing substrates, as proven by laser-induced time-resolved transient absorption spectroscopic measurements. Furthermore, the proposed deuteration method could be applied to various S-containing substrates including pharmaceuticals and biologically active compounds with high regioselectivities. The available deuterated compounds as novel deuterated alkylation reagents for future drug discovery and as materials for Raman imaging were also demonstrated.
4) Photocatalytic Multiple Deuteration of Polyethylene Glycol Derivatives Using Deuterium Oxide
R. Ogasahara, M. Mae, K. Matsuura, S. Yoshimura, T. Ishimoto, T. Udagawa, K. Harada, H. Fujioka, M. Kamiya, R. Asada, H. Uchiyama, Y. Tozuka, S. Akai, Y. Sawama*
Chem. Eur. J. 2025, e202404204
doi.org/10.1002/chem.202404204
Abstract: Deuterated molecules are of growing interest because of the specific characteristics of deuterium, such as stronger C-D bonds being stronger than C-H bonds. Polyethylene glycols (PEGs) are widely utilized in scientific fields (e.g., drug discovery and material sciences) as linkers and for the improvement of various properties (solubility in water, stability, etc.) of mother compounds. Therefore, deuterated PEGs can be used as novel tools for drug discovery. Although the H/D exchange reaction (deuteration) is a powerful and straightforward method to produce deuterated compounds, the deuteration of PEGs bearing many unactivated C(sp3)-H bonds has not been developed. Herein, we report the photocatalytic deuteration of multiple sites of PEGs using tetra-n-butylammonium decatungstate (TBADT) and D2O as an inexpensive deuterium source. This deuteration can be adapted to PEG derivatives bearing various substituents ((hetero)aryl, benzoyl, alkyl, etc.). The deuteration efficiencies of the a-oxy C(sp3)-H bonds at the terminal positions of the PEGs were strongly influenced by the substituents. These reactivities were elucidated by density functional theory calculations of the reaction barriers towards the formation of radical intermediates, induced by the excited state of TBADT and the PEG substrate. In addition, the applicability of deuterated PEGs to internal standard experiments and Raman spectroscopy was demonstrated.
3) Total synthesis of aloin via regioselective Diels–Alder reactions connecting two 3-silylbenzynes and 2-stannylfuran
S. Moriyama, Y. Emi, T. Nosaki, Y. Morikawa, T. Shigeta, A. Takagi, M. Egi, T. Ikawa, Y. Sawama, S. Akai,*
Synlett 2025, 36, A–E
DOI: 10.1055/a-2542-3481
Abstract: The first synthesis of aloin, a natural anthrone C-glycoside, was achieved via two sequential Diels–Alder (DA) reactions connecting 3-silyl-benzynes and 2-stannylfuran. The silyl and stannyl substituents contributed to the regioselectivity of the two DA reactions and the 9,10-ether cleavage of the DA adduct. The subsequent conversion of silyl groups to hydroxyl groups and C10-glycosylation completed the synthesis of aloin.
2) (S)-Convergent Deracemization of Racemic Esters with (R)-Selective Lipase: Pickering Emulsion Strategy for Enantiodivergent Synthesis Using a Native Enzyme
Tomoya Nishio, Shuji Akai, Kyohei Kanomata
ACS Catal. 2025, 15, 6565–6571.
大阪大学リポジトリOUKA（オープンアクセス）https://hdl.handle.net/11094/100944（2026-4-7公開）
Abstract: Catalytic synthesis of both enantiomers of a chiral molecule typically requires both enantiomers of chiral catalysts. However, a number of chiral catalysts for asymmetric transformations, including enzymes, are naturally available in only one enantiomeric form. In this study, we present an enantiodivergent strategy for enzymatic transformations using a single native enzyme. Specifically, we developed an (S)-convergent deracemization process for racemic esters using a native (R)-selective lipase. The transformation was achieved by integrating three reactions into a single system: (1) lipase-catalyzed (R)-selective hydrolysis of a racemic ester, (2) H2SO4-catalyzed racemization of the resulting (R)-alcohol, and (3) esterification of the racemized alcohol. The use of a Pickering emulsion as the reaction medium facilitated the combination of these inherently incompatible processes by compartmentalizing these reactions. Complementary to the conventional (R)-selective transformation, this approach enables the enantiodivergent synthesis of a wide range of sec-alcohols and their corresponding esters using the same native lipase.
1) Racemization of chiral sulfoxide using an immobilized oxovanadium catalyst
Tomoya Nishio, Hajime Shigemitsu, Toshiyuki Kida, Shuji Akai, Kyohei Kanomata
Bull. Chem. Soc. Jpn. 2025, 98, uoae144.
DOI: 10.1093/bulcsj/uoae144
大阪大学リポジトリOUKA（オープンアクセス）https://hdl.handle.net/11094/99973（2025-12-28公開）
Abstract: Racemization of optically active compounds is an essential process in asymmetric transformations such as dynamic kinetic resolution and deracemization. In this study, the racemization of chiral sulfoxides under mild thermal conditions was realized using a novel silica-gel-supported oxovanadium catalyst. Specifically, we screened reaction conditions, analyzed the substrate scope, and conducted mechanistic studies of the silica-gel-supported oxovanadium-catalyzed racemization of sulfoxides. The racemization reaction has a wide substrate scope, including alkyl aryl sulfoxides and diaryl sulfoxides. The catalyst could be reused by exploiting its heterogeneous nature. Mechanistic studies suggested that racemization proceeds via the formation of a radical cation intermediate mediated by the oxovanadium(V)/(IV) redox cycle.