Masayasu Akiyama

N-hydroxy amides. Part 5. Synthesis and properties of N-hydroxypeptides having leucine enkephalin sequences

In order to study the effects of the N-hydroxy amide group, N-hydroxyenkephalin analogues with the H-Tyr-(HO)X-Gly-Phe-Leu-OH sequence, where X = Gly, L-Ala, or β-Ala, have been synthesized. A 1H n.m.r. study indicates that the N-hydroxyenkephalins have a type I β-turn structure in dimethyl sulphoxide solution. From the interaction of (HO)Gly- and β-(HO)Ala-analogues with CuII it is suggested that the hydroxyamide function exerts a definite influence on the complexation. These N-hydroxy enkephalins are resistant to aminopeptidase M. A qualitative analgesia test shows that the (HO)Ala-analogue possesses a more lasting potency than that of Leu5-enkephalin, while having a comparable activity.

N-hydroxy amides. Part 9. Synthesis and lron(III) complexes of tripodal hydroxamic acids derived from ω-(N-hydroxyamino)alkanoic acids and tris(2-aminoethyl)amine

Tripodal oligoamide hydroxamic acids with different chain lengths (compounds 8a–d) are prepared via condensation of N-hydroxysuccinimide esters of N-acyl-N-benzyloxyaminoalkanoic acids with tris-(2-aminoethyl)amine. These synthetic trihydroxamic acids form iron(III) complexes in aqueous DMF solution. The behaviour of these iron(III) complexes is investigated in terms of absorption vs pH and of iron(III) exchange reactions with EDTA. A biological assay performed with Aureobacterium flavescens reveals that the trihydroxamic acids have substantial growth-promoting activity although weak relative to that of natural desferrioxamine B.

N-hydroxy amides. Part 8. Synthesis and iron(III)-holding properties of di- and tri-hydroxamic acids extending from benzene-di- and -tri-carbonyl units through oligo(ethyleneoxy) arms

Benzene-ring centred di- and tri-hydroxamic acids (9a–c and 10a–c) having oligo(ethyleneoxy) chains are prepared by reaction of benzene-di- and -tri-carbonyl chlorides with amino [oligo(ethyleneoxy]ethyl hydroxylamine derivatives (6a–c). Trihydroxamic acids (10a–c) form more stable iron(III) complexes than dihydroxamic acids (9a–c) in several respects. In iron(III) transport experiments using a H2O–CHCl3/CCl4 system, however, compounds (9a–c) show greater rates than compounds (10a–c). The number of ethyleneoxy units in the arm apparently influences these iron(III) holding properties and the iron-transport rates.

Synthesis of linear and cyclic trihydroxamic acids as models for ferrioxamines E and G

Linear and cyclic trihydroxamic acids including the 6-aminohexanoyl-3-(hydroxyamino)propanoyl sequence have been synthesized in a stepwise manner from the appropriately protected acyl derivatives and used as iron(III) chelating compounds.

General acid catalytic activity of 2-substituted imidazoles for hydrolysis of diethyl phenyl orthoformate

Hydrolysis of diethyl phenyl orthoformate catalysed by a series of 2-substituted imidazoles has been studied in 50% dioxane–water (v/v) at 30 °C. The substituents are H, Me, Et, Pri, But, 2-hydroxypropyl, and 1,1-dimethyl-2-hydroxyethyl groups. General acid catalysis is observed for hydrolysis by these imidazoles but not general base catalysis. The rate data are analysed in terms of the second-order rate constants for imidazoles versus the Taft steric constant parameter, Es. The steric effect of substituents is small. Activation parameters determined for a few imidazoles contain large negative entropies. These results and a D2O solvent isotope effect indicate that solvent water molecules participate in the transition state of the reaction.