137378-58-6Relevant academic research and scientific papers
Rapid Synthesis of Boc-2′,6′-dimethyl- l -tyrosine and Derivatives and Incorporation into Opioid Peptidomimetics
Bender, Aaron M.,Griggs, Nicholas W.,Gao, Chao,Trask, Tyler J.,Traynor, John R.,Mosberg, Henry I.
, p. 1199 - 1203 (2015)
The unnatural amino acid 2′,6′-dimethyl-l-tyrosine has found widespread use in the development of synthetic opioid ligands. Opioids featuring this residue at the N-terminus often display superior potency at one or more of the opioid receptor types, but the availability of the compound is hampered by its cost and difficult synthesis. We report here a short, three-step synthesis of Boc-2′,6′-dimethyl-l-tyrosine (3a) utilizing a microwave-assisted Negishi coupling for the key carbon-carbon bond forming step, and employ this chemistry for the expedient synthesis of other unnatural tyrosine derivatives. Three of these derivatives (3c, 3d, 3f) have not previously been examined as Tyr1 replacements in opioid ligands. We describe the incorporation of these tyrosine derivatives in a series of opioid peptidomimetics employing our previously reported tetrahydroquinoline (THQ) scaffold, and the binding and relative efficacy of each of the analogues at the three opioid receptor subtypes: mu (MOR), delta (DOR), and kappa (KOR).
Development of potent μ-opioid receptor ligands using unique tyrosine analogues of endomorphin-2
Li, Tingyou,Fujita, Yoshio,Tsuda, Yuko,Miyazaki, Anna,Ambo, Akihiro,Sasaki, Yusuke,Jinsmaa, Yunden,Bryant, Sharon D.,Lazarus, Lawrence H.,Okada, Yoshio
, p. 586 - 592 (2007/10/03)
Six analogues of tyrosine, which contained alkyl groups at positions 2′, 3′, and 6′, either singly or in combination on the tyramine ring, were investigated for their effect on the opioid activity of [Xaa1]endomorphin-2 (EM-2). The opioid analo
