137650-15-8

Upstream product

• 7463-51-6 4-bromo-3,5-dimethylphenol 
• 93267-04-0 N-(tert-butoxycarbonyl)-L-3-iodoalanine methyl ester 
• 2766-43-0 N-tert-butyloxycarbonyl-L-serine methyl ester 
• 80826-86-4 4-iodo-3,5-dimethylphenol 

Downstream Products

• 137650-16-9 N-<(1,1-dimethylethoxy)carbonyl>-O-(1,1-dimethylethyl)-2,6-dimethyl-L-tyrosine methyl ester 
• 623950-03-8 methyl (S)-2-((tert-butoxycarbonyl)amino)-3-(2,6-dimethyl-4-(((trifluoromethyl)sulfonyl)oxy)phenyl)propanoate 
• 99953-00-1 (S)-N-Boc-2,6-dimethyltyrosine 
• 861676-21-3 4'-morpholinylcarbonyl N-Boc-2',6'-dimethyl-L-phenylalanine methyl ester 
• 861676-20-2 4'-ethylcarbamoyl N-Boc-2',6'-dimethyl-L-phenylalanine methyl ester 
• 861676-19-9 methyl (S)-2-((tert-butoxycarbonyl)amino)-3-(2,6-dimethyl-4-(methylcarbamoyl)phenyl)propanoate 
• 623950-02-7 (S)-2-((tert-butoxycarbonyl)amino)-3-(4-carbamoyl-2,6-dimethylphenyl)propanoic acid 
• 623950-05-0 methyl (S)-2-((tert-butoxycarbonyl)amino)-3-(4-carbamoyl-2,6-dimethylphenyl)propanoate 
• 623950-04-9 4'-carboxyl N-Boc-2',6'-dimethyl-L-phenylalanine methyl ester 
• 137650-24-9 5-<1-amino-2-(4-hydroxy-2,6-dimethylphenyl)ethyl>-1,5-dihydro-3-methyl-1-(3-phenylpropyl)-2H-pyrrol-2-one hydrochloride 
• 137650-28-3 5(S)-amino-6-(4-hydroxy-2,6-dimethylphenyl)-N-(3-phenylpropyl)-3(E)-hexenamide hydrochloride 
• 137650-30-7 δ(R)-amino-4-hydroxy-2,6-dimethyl-N-(3-phenylpropyl)benzenehexanamide hydrochloride 
• 137650-23-8 1,1-dimethylethyl <1(S)-<<4-(1,1-dimethylethoxy)-2,6-dimethylphenyl>methyl>-4-methyl-2,5-dioxo-5-<(3-phenylpropyl)amino>pentyl>carbamate 
• 137650-22-7 1,1-dimethyl <2-1(S)-<<4-(1,1-dimethylethoxy)-2,6-dimethylphenyl>methyl>-4-methylene-2,5-dioxo-5-<(3-phenylpropyl)amino>pentyl>carbamate 

Relevant academic research and scientific papers

OPIOID RECEPTOR MODULATORS AND PRODUCTS AND METHODS RELATED THERETO

Compounds are provided having the structure of Formula (I): or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof, wherein A, B, L, R3, R4, R5, R6, R8, m and n are as defined herein. Such compounds modulate the opioid receptor, particulare the mu-opioid receptor (MOR) and/or the kappa-opioid receptor (KOR), and/or the delta-opioid receptor (DOR). Products containing such compounds, as well as methods for their use and preparation, are also provided.

Rapid Synthesis of Boc-2′,6′-dimethyl- l -tyrosine and Derivatives and Incorporation into Opioid Peptidomimetics

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).