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Synthesis of empagliflozin, a novel and selective sodium‐glucose co‐transporter‐2 inhibitor, labeled with carbon‐14 and carbon‐13
Author(s) -
Hrapchak Matt,
Latli Bachir,
Wang XiaoJun,
Lee Heewon,
Campbell Scot,
Song Jinhua J.,
Senanayake Chris H.
Publication year - 2014
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3240
Subject(s) - empagliflozin , chemistry , radiosynthesis , yield (engineering) , carbon 14 , carbon fibers , phenol , d glucose , radiochemistry , organic chemistry , stereochemistry , diabetes mellitus , type 2 diabetes mellitus , in vivo , medicine , materials science , physics , microbiology and biotechnology , quantum mechanics , endocrinology , composite number , metallurgy , composite material , biology
Empagliflozin, (2 S ,3 R ,4 R ,5 S ,6 R )‐2‐[4‐chloro‐3‐[[4‐[(3 S )‐oxolan‐3‐yl]oxyphenyl]methyl]phenyl]‐6‐(hydroxymethyl)oxane‐3,4,5‐triol was recently approved by the FDA for the treatment of chronic type 2 diabetes mellitus. Herein, we report the synthesis of carbon‐13 and carbon‐14 labeled empagliflozin. Carbon‐13 labeled empagliflozin was prepared in five steps and in 34% overall chemical yield starting from the commercially available α‐D‐glucose‐[ 13 C 6 ]. For the radiosynthesis, the carbon‐14 atom was introduced in three different positions of the molecule. In the first synthesis, Carbon‐14 D‐(+)‐gluconic acid δ‐lactone was used to prepare specifically labeled empagliflozin in carbon‐1 of the sugar moiety in four steps and in 19% overall radiochemical yield. Carbon‐14 labeled empagliflozin with the radioactive atom in the benzylic position was obtained in eight steps and in 7% overall radiochemical yield. In the last synthesis carbon‐14 uniformly labeled phenol was used to give [ 14 C]empagliflozin in eight steps and in 18% overall radiochemical yield. In all these radiosyntheses, the specific activities of the final compounds were higher than 53 mCi/mmol, and the radiochemical purities were above 98.5%.