Synthesis of 6‐Amino Acid Substituted Derivatives of the Highly Potent Analgesic 14‐O‐Methyloxymorphone

The novel morphinans 13 – 18 , which carry amino acid substituents at C(6), with potentially limited access to the central nervous system were prepared in two steps from 14‐O‐methyloxymorphone ( 5 ). Reductive amination with amino acid tert‐butyl esters gave compounds 7 – 12 , which were hydrolyzed with tetrafluoroboric acid. Structure elucidation (including X‐ray analysis), preliminary μ‐opioid receptor binding studies, and calculations of pharmacokinetic parameters were carried out.