Effect of temperature on the acidolysis of N-acyl-N,alpha,alpha-trialkyl glycine amides as related to the nature of substituents.

The C-terminal amide bond of N-acyl-N,alpha,alpha-trialkyl glycine amides is labile to acid and this has been currently assigned to steric crowding within the amino acid residue. However, our previous work has shown that in the acidolysis of some of these compounds steric hindrance seems to play a less important role than what one would expect. Thus, the cleavage of two sets of such compounds bearing different degrees of crowding was investigated at five different temperatures in order to clarify the effect of structure on reactivity in terms of enthalpy and entropy of activation.

Kinetic investigation of the effect of the amino acid side chains in the selective acidolysis of N-acyl-N,alpha,alpha-trialkyl glycine amides.

Accurate kinetic measurements of the rate constants for the acidolysis of five N-acetyl-N-(4-methoxybenzyl)-alpha,alpha-trialkyl glycine cyclohexyl amides in TFA were performed at 25 degrees C and the reactions monitored by HPLC. In all cases the results were consistent with a first order behaviour with respect to the substrate. No direct correlation was obtained with these data between the rate constant values and structure, but a good correlation coefficient was obtained when a multiple regression analysis was applied by taking advantage of a Taft equation using appropriate polar and steric substituent parameters.

Kinetic and mechanistic investigation of the selective acidolysis of the C-terminal amide bond of N-acyl-N,alpha,alpha-trialkyl glycine amides.

Accurate rate constants were calculated from HPLC kinetic measurements of the selective acidolysis of the C-terminal amide bond of eight N-acyl-N-(4-methoxybenzyl)-alpha,alpha-trialkyl glycine amides in TFA at 25.00 degrees C. The results were in all cases consistent with a first order behaviour with respect to the substrate and, apparently, also to the acid, and a clear relationship between reactivity and structure could be observed.

Synthesis of N-acyl-N,alpha,alpha-trialkyl and N-acyl-alpha,alpha-dialkyl glycines by selective cleavage of Ugi-Passerini adducts. Qualitative assessment of the effect of substituents on the path and yield of reaction.

Several symmetric N-acyl-N,alpha,alpha-trialkyl glycine amides were synthesised by the Ugi-Passerini four-component reaction and subjected to selective cleavage with trifluoroacetic acid. In almost all cases it was possible to obtain the corresponding N-acyl-N,alpha,alpha-trialkyl and N-acyl-alpha,alpha-dialkyl glycines in fair to good yields directly from the reaction adducts. With some of the bulkier compounds our results show that the selectivity of cleavage is concentration dependent with respect to the acid, which suggests kinetically controlled processes.

Cytotoxic bis-3,4-dihydro-beta-carbolines and bis-beta-carbolines.

Ten bis-beta-carboline 1, 2 and bis-3,4-dihydro-beta-carboline 3, 4 derivatives, linked between carbons 1 and 1' by a polymethylene spacer, were synthesized from bistryptamine amides 9, 10. Some of them display a micromolar IC50 towards L-1210 cells.