Terminal Side-Chain Position

Absorption maxima for the 1 1 Cu(II)-tripeptide complexes occur near 550 nm (e = ca. 150). Most of these complexes show only a single negative CD extremum at about 560 nm for bands II and III. Two tripeptide complexes with bulky NH 2-terminal side chains exhibit single positive extrema. 

FIGURE 27 19 Proposed mechanism of hydrolysis of a peptide catalyzed by carboxypeptidase A The peptide is bound at the active site by an ionic bond between its C terminal ammo acid and the positively charged side chain of arginine 145 Coordination of Zn to oxygen makes the carbon of the carbonyl group more positive and increases the rate of nucleophilic attack by water... 

This four-atom replacement was observed in some reactions of uracil derivatives, containing at position 5 a substituent with the CCCN moiety. Treatment of the Z-isomer 5-(2-carbamoylvinyl)-l,3-dialkyluracil with ethanolic sodium ethoxide gave in good yield 3-ethoxycarbonylpyridin-6(lf/)-one (84%) together with 3-A-methylcarbamoyl)pyridin-6-(l7 )-one (10%) (85JOC1513) (Scheme 26). The reaction involves an initial attack of the terminal amino group of the side-chain on position 6 of the uracil molecule. C-6-N-1 bond fission and N-C bond formation yield the pyridin-6(l//)-one. A subsequent attack of the ethoxide ion on the carbonyl groups of the side-chain yields both pyridin-2-one derivatives (Scheme 26). Similar results were obtained with the -isomer. 

Substitution of an additional nitrogen atom onto the three-carbon side chain also serves to suppress tranquilizing activity at the expense of antispasmodic activity. Reaction of phenothia zine with epichlorohydrin by means of sodium hydride gives the epoxide 121. It should be noted that, even if initial attack in this reaction is on the epoxide, the alkoxide ion that would result from this nucleophilic addition can readily displace the adjacent chlorine to give the observed product. Opening of the oxirane with dimethylamine proceeds at the terminal position to afford the amino alcohol, 122. The amino alcohol is then converted to the halide (123). A displacement reaction with dimethylamine gives aminopromazine (124). ... 

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