99953-00-1Relevant articles and documents
2',6'-dimethyltyrosine derivative and C-H activation methylation synthesis method thereof
-
Paragraph 0270 - 0272, (2018/04/01)
The present invention provides a 2',6'-dimethyltyrosine derivative and a C-H activation methylation synthesis method thereof, specifically a compound represented by the following formula I, wherein each group is defined in the specification. The invention further provides a preparation method of the compound. The formula I is defined in the specification.
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.
supporting information, p. 1199 - 1203 (2015/12/23)
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).
Studies on the structure-activity relationship of 2′,6′- dimethyl-l-tyrosine (Dmt) derivatives: Bioactivity profile of H-Dmt-NH-CH 3
Fujita, Yoshio,Tsuda, Yuko,Motoyama, Takashi,Li, Tingyou,Miyazaki, Anna,Yokoi, Toshio,Sasaki, Yusuke,Ambo, Akihiro,Niizuma, Hideko,Jinsmaa, Yunden,Bryant, Sharon D.,Lazarus, Lawrence H.,Okada, Yoshio
, p. 599 - 602 (2007/10/03)
The 2′,6′-dimethyl-l-tyrosine (Dmt) enhances receptor affinity, functional bioactivity and in vivo analgesia of opioid peptides. To further investigate its direct influence on these opioid parameters, we developed a series of compounds (H-Dmt-NH-X). Among them, H-Dmt-NH-CH3 showed the highest affinity (Kiμ = 7.45 nM) equal to that of morphine, partial μ-opioid agonism (Emax = 66.6%) in vitro and a moderate antinociception in mice.