Solid-phase synthesis of lidocaine analogues using backbone amide linker (BAL) anchoring

摘要

Previous studies from our laboratory reported on Backbone Amide Linker (BAL) anchoring approaches for solid-phase syntheses of C-terminal modified and cyclic peptides,diketopiperazines,peptide aldehydes,unprotected peptide p-nitroanilides and thioesters,and peptides containing prolyl,N-alkylaminoacyl,and histidyl groups at the C-terminus.The BAL methodology and variations have been extended to the solid-phase syntheses of non-peptidic small organic molecules such as benzodiazepines,hydroxamic acids,2,9-substituted purines,modified amino sugars,1,3-bis(acylamino)-2-butanones,benzimidazoles,hapalosin mimetics,quinoxalinones,heterocyclic ethylenediamine-derivatized libraries,N,N'-disubstituted ureas,and perhydroimidazol[1,5-a]pyrazines.As an addition to the types of compounds accessible via BAL anchoring,we describe herein an attractive solid-phase synthesis of lidocaine,a common antiarrhythmic drug,and several analogues.