Anilide, peptide derivatives

Ca. 2.1 moles aniline in ether added slowly to a soln. of the startg. m. in anhydrous ether, and allowed to stand 12 hrs. at room temp. N-trifluoroacetyl-dehydrophenylalanine anilide. Y 83%. F. e., also peptide derivs., s. E. G. Breit-holle and C. H. Stammer, J. Org. Chem. 47, 1344 (1976). 

The use of benzimidazolone derivatives 4, prepared from the anilides 3, for the thioacylation of peptides (Scheme 4) have also been reported, 27 and three thioamide analogues of tuftsin were prepared. Due to the acid lability of thioamides, Boc deprotection with SnCl4 represents a mild alternative for N-terminal extension.12 ... 

Recently, a mild, efficient and racemization-free route for the incorporation of a thioamide linkage into a peptide either in solution or on solid phase was provided by Shalaby et al. [127], First, the N-Boc-amino acid anilide derivative was thionylated with P4St0 and subsequently activated by transformation to the benzotriazole derivative, affording a stable thioacylating reagent (Scheme 7.8) suitable for combinatorial syntheses. 

Most of the enzymatic peptide forming reactions are strictly stereo-specific for L-amino acids so that racemization that often accompanies chemical coupUng of optically active amino acids does not occur. The formation of only the L-amino acid derivative out of a D,L-mixture, in an enzymatic formation e.g. of an anilide from a D,L-Z-amino acid ester and aniUne, makes proteolytic enzymes useful reagents for the resolution of racemic mixtures. This is supplementary to the enzymatic stereospecific deacylation of D,L-iV-acylamino acid mixtures where exclusively the L-derivative will be deacylated. 

One may include in this category the synthesis by chymotrypsin of benzoyl-L-tyrosylglycineamide in low yield from an 0.02M solution of benzoyl-L-tyrosine and glycineamide, although the amide radical of the peptide was eventually hydrolyzed off (46). In all these reactions the enzyme was specific for the L-form of the amino acid derivative participating in the reaction even in the reaction of acetyl-DL-phenylalanylglycine with aniline, only acetyl-L-phenylalanylglycine anilide was formed,... 

Following publication by Weygand and coworkers 432, 433) of their studies of the bromination of 2-trifluoroacetyl-A -oxazolinones at the p-carbon atom of the corresponding amino acid, Breitholle and Stammer (68, 69) described the elimination of HBr from these bromo-derivatives (17) to yield unsaturated A -oxazolinones (18). The latter yielded N-trifluoroacetyldehydroamino acid anilides (19) or peptides on treatment with aniline or amino acid esters respectively. Muller and Steglich (270) used this method independently for the synthesis of N-trifluoroacetyl-dehydrodipeptides (20) containing C-terminal alanine. 

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