Convergent and stereospecific synthesis of molecules containing α-functionalized guanidiniums via α-guanidino acids

Article abstract of DOI:10.1021/jo701766c

(Chemical Equation Presented) To introduce chirality and functional groups adjacent to guanidiniums to modulate specificity and affinity in recognition, N,N′-bis(Boc)-α-guanidino acids were synthesized from α-amino acid methyl esters. Protected α-guanidino acids coupled to cyclohexylamine and trans-1,4-diaminocyclohexane 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 deprotected guanidinium is configurationally stable under more acidic conditions. This approach represents a practical, convergent, stereospecific methodology to introduce chiral α-substituted guanidinium groups into molecules.