A NEW APPROACH TO PHOSPHOSERINE, PHOSPHOTHREONINE AND PHOSPHOTYROSINESYNTHONS AND TO THIOPHOSPHO ANALOGS - STEPWISE SYNTHESIS OF MONO-PHOSPHORYLATED AND MULTIPHOSPHORYLATED PHOSPHOPEPTIDES RELATED TO SRC-PROTEIN KINASE

Several phosphoserine, phosphothreonine and phosphotyrosine synthons s uitable for the stepwise synthesis of phosphopeptides were prepared. T reatment of methylthiomethyl (MTM) esters of either Z-, Boc-, Allocser ine and threonine with phosphochloridate in pyridine followed by MgBr2 cleavage of MTM in diethyl ether afforded the title compounds in good yield. Thiophosphoserine and phosphotyrosine synthons were also obtai ned by the phosphoramidite method using 2,2-trichloroethyl)-N,N-diisop ropylphosphoramidite and MCPBA as oxidizing reagent. Trichloroethyl pr oved valuable as phosphate protecting group especially in phosphotyros ine derivatives owing to its stability in acidic conditions. These syn thons were involved in the liquid-phase synthesis of several phospho a nd/or thiophosphopeptides related to either are-protein kinase or rat liver pyruvate kinase. (C) Munksgaard 1995.