Versatile phosphoranes as linker reagents:Access to various isostere structures for protease inhibition via smooth C-C-couplings on polymer support

摘要

Norstatine,diaminopropanole and statine isosteres incorporated in a peptidic environment represent major structural units for aspartate protease inhibition.Recently,we demonstrated the acylation of polymer-supported cyanomethylene triphenylphosphoranes as the key step in the solid phase assembly of alpha-hydroxy-beta-amino esters and amides(norstatines).In this linker reagent concept,the phosphoranes perform a double task:first they act as a carbanionic polymer reagent for CC-coupling reactions and in the second step-as a linker-they allow for versatile variation and cleavage of the immobilized products.We now present an extension of this linker reagent approach towards alkoxycarbonyl methylenphosphoranes.