title: Development of a Scalable Synthesis of Tofogliflozin.
abstract: 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.
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Ohtake
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Emura
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishimoto
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Takano
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsuchiya
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan.
authors.forename: Sang-Yong
authors.initials: SY
authors.lastname: Yeu
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kito
authors.affiliation: Pharmaceutical Technology Division, Chugai Pharmaceutical Co., Ltd., 5-5-1 Ukima, Kita-ku, Tokyo 115-8543, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Kimura
authors.affiliation: Pharmaceutical Technology Division, Chugai Pharmaceutical Co., Ltd., 5-5-1 Ukima, Kita-ku, Tokyo 115-8543, Japan.
authors.forename: Sunao
authors.initials: S
authors.lastname: Takeda
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Tsukazaki
authors.affiliation: Pharmaceutical Technology Division, Chugai Pharmaceutical Co., Ltd., 5-5-1 Ukima, Kita-ku, Tokyo 115-8543, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Murakata
authors.affiliation: Research Division, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sato
mesh_terms: D001559:Benzhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D005947:Glucose / Q000737:chemistry*; D005960:Glucosides / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D051297:Sodium-Glucose Transporter 2 / Q000737:chemistry*; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D005947:Glucose; C575086:6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol