Convergent and stereospecific synthesis of molecules containing alpha-functionalized guanidiniums via alpha-guanidino acids.
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 alpha-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 alpha-substituted guanidinium groups into molecules.
Balakrishnan
Shalini
S
Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, USA.
Zhao
Chen
C
Zondlo
Neal J
NJ
D000596:Amino Acids / Q000737:chemistry; D003514:Cyclohexylamines / Q000737:chemistry; D019791:Guanidine / Q000737:chemistry*; D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry*; D008968:Molecular Conformation; D013237:Stereoisomerism
D000596:Amino Acids; D003514:Cyclohexylamines; D006146:Guanidines; C088969:1,4-diaminocyclohexane; D019791:Guanidine