URETHANE PROTECTED AMINO-ACID N-CARBOXYANHYDRIDES AND FLUORIDES (U-NCAS AND U(2)AAFS)

In order to obtain peptide analogues containing a central pyrrolide bo nd, as potential mechanism-based inhibitors of the HIV-1 proteinase, a ctivated derivatives of amino acids were required. Treatment of a N,N- bis(Boc) amino acid pyridinium salt with cyanuric fluoride in dichloro methane furnished the corresponding bis(Boc) amino acid fluoride (Boc( 2)AAF). Use of the Vilsmeier reagent in acetonitrile, instead of the c yanuric fluoride, led to a N-Boc amino acid N-carboxyanhydride (Boc-NC A). From a mixed N-Z,N-Boc amino acid salt a N-Z,N-Boc amino acid fluo ride and a Z-NCA were respectively obtained. The very sensitive Young test showed that during the coupling of the N-benzoyl-L-Leucine N-carb oxyanhydride or the N-benzoyl N-Boc-L-leucyl fluoride with ethyl glyci nate the degrees of racemization were weak. Owing to the electronegati vity and the small size of the fluorine atom, the bis(urethane) amino acid fluorides are efficient acylating agents for amines and pyrrole a nions.