Convergent and Stereospecific Synthesis of Molecules Containing alpha-Functionalized Guanidiniums via alpha-Guanidino Acids

摘要

To introduce chirality and functional groups adjacent to guanidiniums to modulate specificity and affinity in recognition,N,N-bis(Boc)-alpha-guanidino acids were synthesized from alpha-amino acid methyl esters.Protected a-guanidino acids coupled to cyclohexylamine and trans-1,4-diaminocyclo-hexane in good yield and with retention of stereochemistry.Boc deprotection was conducted under mild acidic conditions(0.5 M HCl/EtOAc)to minimize epimerization.The depro-tected guanidinium is configurationally stable under more acidic conditions.This approach represents a practical,convergent,stereospecific methodology to introduce chiral a-substituted guanidinium groups into molecules.