Inventing and understanding catalytic, enantioselective reactions.
This review summarizes recent advances in the development of efficient routes based on enantioselective catalysis for the synthesis of optically active therapeutic agents. Particular emphasis is placed on research that has streamlined the large-scale production of therapeutics for the treatment of type 2 diabetes mellitus (T2DM). Progress in the catalytic asymmetric hydrogenation and amination of unprotected substrates has enabled the establishment of concise synthetic routes for the production of the potent dipeptidyl peptidase 4 inhibitor sitagliptin, and the aldose reductase inhibitor ranirestat (Dainippon Sumimoto Pharma Co Ltd/Eisai Co Ltd/ Kyorin Pharmaceutical Co Ltd), both of which have attracted particular attention for their potential to treat T2DM and diabetic complications, respectively.
Shibasaki
Masakatsu
M
The University of Tokyo, Graduate School of Pharmaceutical Sciences, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. mshibasa@mol.f.u-tokyo.ac.jp
Kumagai
Naoya
N
Mashiko
Tomoyuki
T
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000586:Amination; D002384:Catalysis; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis; D006865:Hydrogenation; D007004:Hypoglycemic Agents / Q000138:chemical synthesis*; D008956:Models, Chemical; D015394:Molecular Structure; D011719:Pyrazines / Q000138:chemical synthesis*; D000068900:Sitagliptin Phosphate; D013141:Spiro Compounds / Q000138:chemical synthesis*; D013237:Stereoisomerism; D014230:Triazoles / Q000138:chemical synthesis*
D054873:Dipeptidyl-Peptidase IV Inhibitors; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D011719:Pyrazines; D013141:Spiro Compounds; D014230:Triazoles; D000449:Aldehyde Reductase; D000068900:Sitagliptin Phosphate; C115070:ranirestat