Reduction of Methionine Sulfoxide Containing Peptides [1]

Abstract

Freshly distilled thioglycolic acid [2, 3] (0.92 g, 0.70 ml, 10 mmol) is added to a suspension of l-prolyl-l-tyrosyl-N^ε-tosyl-l-lysyl-l-methionine-sulfoxide (0.71 g, 1.0 mmol) in distilled water (5 ml) and the reaction mixture is stored under nitrogen at 50 °C. A clear solution forms from which the product gradually separates as an oil. After about 20 h the mixture is evaporated in vacuo and the residual oil triturated with ether, the ether decanted and replaced with fresh ether. Trituration is continued until a solid material is obtained. This is dissolved in a small volume of methanol and the solution made slightly alkaline by the addition of a 2.5 M solution of NH₃ in methanol. The mixture is cooled in an ice water bath and the crystalline product which separates from the solution is collected after about 30 min. It is extracted with hot methanol and refiltered. The reduced (still partially protected) tetrapeptide (0.60 g, 87%) melts at 223–226 °C; [α] ²⁶_D −14° (c 4, acetic acid). It is chromatographically homogeneous and gives the expected values on elemental analysis.