Synthesis of 2-[2-(-butoxycarbonyl)-3-(acyl)guanidino]ethylamine salts for convergent introduction of acyl guanidines

Convergent, late-stage introduction of acylguanidine moieties is a useful strategy for the rapid development of novel compounds containing functionalised guanidines. As such, robust methodology for suitable acylguanidine building blocks is required. Here the synthesis of a range of 2-[2-( tert -butoxycarbonyl)-3-(acyl)guanidino]ethylamine salts is reported using the reaction of readily prepared acyl substituted S -methylisothioureas with ethylenediamine then conversion of these aminoethylacylguanidines to salts (using HCl or MsOH). A wide range of acyl groups were tolerated, with the desired salts being isolated in good yields (52-86% over two steps). Introduction of one of the new acylguanidine reagents to an organic scaffold was readily accomplished to generate a new antimicrobial agent. A series of acylguanidines with pre-installed ethylamino linkers are described that can be incorporated into larger structures through amide coupling.