| 摘要 |
PURPOSE:To prepare a thiol compound having antihypertensive activity, in high yield and purity, by reacting an N-haloalkanoylamino acid with a thiolating reagent comprising a salt of hydrogen sulfide and ammonia or an organic base. CONSTITUTION:A thiol compound of formula II [n is 1-3; R1 is H or CH3; Y is O, S, SO, SO2, etc.; R2 is OH or group of formula III (both R3 and R4 are H, or R3 is H and R4 is amino acid residue)] e.g. N-(3-mercapto-2-D-methylpropanoyl)- L-proline which is an antihypertensive agent, is prepared by reacting a compound of formula I (X is halogen) or its salt with a salt of hydrogen sulfide and ammonia or an organic base, in an aqueous solution, pref. in the presence of a reduction agent, in an inert gas atmosphere at 30-100 deg.C. It is essential for the suppression of by-products to select the molar ratio of the hydrogen sulfide salt to the compound of formula I to 2-20, and the concentration of the compound of formula I to about 0.01-5M. |
