Facile synthesis of (R)-4-mercaptopyrrolidine-2-thione from L-aspartic acid.
An SN2-type of substitution of (S)-bromide 4, which had been prepared from L-aspartic acid, with potassium thiobenzoate provided (R)-benzoylthio derivative 5 with complete inversion of the configuration. Compound 5 was converted, via iodide 6c, to (R)-4-amino-3-benzoylthiobutyric acid 8b. (R)-4-Mercapto pyrrolidine-2-thione 1 was readily obtained from 8b through cyclization with acetic anhydride, thionation with Lawesson's reagent and facile removal of the S-benzoyl group with sodium methoxide.
Seki
M
M
Product & Technology Development Laboratory, Tanabe Seiyaku Co. Ltd., Osaka, Japan. m-seki@tanabe.co.jp
Shimizu
T
T
D001224:Aspartic Acid / Q000737:chemistry*; D003500:Cyclization; D009682:Magnetic Resonance Spectroscopy; D011759:Pyrrolidines / Q000138:chemical synthesis*; D013055:Spectrophotometry, Infrared; D013439:Sulfhydryl Reagents; D013871:Thiones / Q000138:chemical synthesis*
C414088:4-mercaptopyrrolidine-2-thione; D011759:Pyrrolidines; D013439:Sulfhydryl Reagents; D013871:Thiones; D001224:Aspartic Acid