Verfahren zur Herstellung von Verbindungen mit geschuetzten Aminogruppen

摘要

The invention comprises compounds of the general formula in which R is hydrogen or a C1-C4 alkyl; R1 is hydrogen, C1-C4 alkyl, hydroxy-substituted C1-C4 alkyl, carboxy-substituted C1-C4 alkyl, lower alkyl-mercapto-substituted C1-C4 alkyl, guanidino-substituted C1-C4 alkyl, guanidinooxy-substituted C1-C4 alkyl, imidazolylmethyl, indolylmethyl, thienyl, furyl, phenyl or benzyl; or R and R1 together with the atoms to which they are attached are piperidine or pyrrolidine. The new compounds may be prepared by reacting a compound of formula in which R2 is halo, azido or p-nitrophenoxy with a compound of formula The dimethoxy benzyl derivaitve used as starting material may be obtained (a) by treating 3,5-dimethoxybenzyl alcohol with phosgene to get the 3,5-dimethoxybenzyl chlorocarbonate which may, if desired, be converted to the azide, for example by treatment with hydrazine and subsequent diazotization with an organic nitrite or (b) by treating the 3,5-dimethoxybenzyl alcohol with p-nitrophenyl chlorocarbonate to get the p-nitrophenyl carbonate derivative. Among the new compounds which are made by the process are N-3,5-dimethoxybenzoxycarbonyl L-tyrosine; N-3,5-dimethoxybenzoxycarbonyl alanine; N - 3,5 - dimethoxybenzoxycarbonyl alanine; N - 3,5 - dimethoxybenzoxycarbonyl phenylalanine; N - 3,5 - dimethoxybenzoxycarbonyl a - amino - n - butyric acid; N - 3,5 - dimethoxybenzoxycarbonyl D-valine; N-3,5-dimethoxybenzoxycarbonyl - 2,4 - dichlorophenylalanine and N - 3,5 - dimethoxybenzoxycarbonyl a - aminoadipic acid. Examples are given of the preparation of 3,5-dimethoxybenzyloxycarbonyl derivatives of glycine, phenyl glycine, DL-methionine, L-serine and carbobenzoxy-L-ly-sine. The new compounds may be reacted with another amino acid or a peptide and the protective group then removed by exposing the compound formed to a source of ultra-violet light e.g. 3,5-dimethoxybenzyloxycarbonyl-D-phenylglycine is reacted with glycine to give N - 3,5 - dimethoxybenzyloxycarbonyl - D - phenylglycylglycine which is irradiated with ultra-violet light to give phenylglycylglycine.