Ohtake Yoshihito, Emura Takashi, Nishimoto Masahiro, Takano Koji, Yamamoto Keisuke, Tsuchiya Satoshi, Yeu Sang-Yong, Kito Yasushi, Kimura Nobuaki, Takeda Sunao, Tsukazaki Masao, Murakata Masatoshi, Sato Tsutomu
Research Division, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan.
Research Division, Chugai Pharmaceutical Co., Ltd., 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan.
J Org Chem. 2016 Mar 4;81(5):2148-53. doi: 10.1021/acs.joc.5b02734. Epub 2016 Feb 19.
An efficient and scalable synthesis of an antidiabetic drug, tofogliflozin (1), which was identified as a highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor, is described. A key factor in the synthesis of 1 was the selection of the purpose-designed protecting group, which plays a strategic role in protection, chemoselective activation, and crystalline purification. The developed and optimized method made it possible to prepare 1 on a multidecagram scale without any column chromatography.
描述了一种抗糖尿病药物托格列净（1）的高效且可扩展的合成方法，该药物被鉴定为一种高选择性钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂。合成1的关键因素是选择专门设计的保护基团，其在保护、化学选择性活化和结晶纯化中起关键作用。所开发和优化的方法使得无需任何柱色谱法即可在多克规模上制备1。
