111633-04-6

Basic information

• Product Name: (R)-2-((tert-butoxycarbonyl)aMino)-3-(4-hydroxy-2,6-diMethylphenyl)propanoic acid
• Synonyms: (R)-2-((tert-butoxycarbonyl)aMino)-3-(4-hydroxy-2,6-diMethylphenyl)propanoic acid
• CAS NO: 111633-04-6
• Molecular Formula: C16H23NO5
• Molecular Weight: 309.35752
• Mol File: 111633-04-6.mol

Chemical Properties

• Boiling Point: 512.0±50.0 °C(Predicted)
• Appearance: /
• Density: 1.191±0.06 g/cm3(Predicted)
• PKA: 3.06±0.10(Predicted)
• CAS DataBase Reference: (R)-2-((tert-butoxycarbonyl)aMino)-3-(4-hydroxy-2,6-diMethylphenyl)propanoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-2-((tert-butoxycarbonyl)aMino)-3-(4-hydroxy-2,6-diMethylphenyl)propanoic acid(111633-04-6)
• EPA Substance Registry System: (R)-2-((tert-butoxycarbonyl)aMino)-3-(4-hydroxy-2,6-diMethylphenyl)propanoic acid(111633-04-6)

Safety Data

• Hazardous Substances Data: 111633-04-6(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Applications:
(R)-2-((tert-butoxycarbonyl)aMino)-3-(4-hydroxy-2,6-diMethylphenyl)propanoic acid is used as an intermediate in the synthesis of various pharmaceutical compounds due to its unique structure and reactivity. Its ability to be incorporated into complex molecules makes it a valuable asset in the development of new drugs.
Used in Chemical Synthesis:
In the chemical synthesis industry, (R)-2-((tert-butoxycarbonyl)aMino)-3-(4-hydroxy-2,6-diMethylphenyl)propanoic acid is used as a key building block for creating a variety of organic compounds. Its versatility in forming different chemical bonds and its stability contribute to its widespread use in this field.
Used in Research and Development:
(R)-2-((tert-butoxycarbonyl)aMino)-3-(4-hydroxy-2,6-diMethylphenyl)propanoic acid is employed as a research compound for studying the properties and behavior of chiral molecules. Its unique structure allows scientists to explore various aspects of stereochemistry and asymmetric synthesis, furthering the understanding of molecular interactions and potential applications in various industries.
Used in Peptide Synthesis:
In the field of peptide synthesis, (R)-2-((tert-butoxycarbonyl)aMino)-3-(4-hydroxy-2,6-diMethylphenyl)propanoic acid is used as a starting material for the development of novel peptides. Its incorporation into peptide sequences can lead to the creation of new bioactive molecules with potential applications in medicine and biotechnology.

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 123715-02-6 H-Dmt 
• 80110-73-2 2,6-dimethyltyrosine hydrochloride 
• 81806-45-3 2',6'-dimethyltyrosine 
• 137650-15-8 methyl (S)-2-((tert-butoxycarbonyl)amino)-3-(4-hydroxy-2,6-dimethylphenyl)propanoate 
• 2766-43-0 N-tert-butyloxycarbonyl-L-serine methyl ester 
• 93267-04-0 N-(tert-butoxycarbonyl)-L-3-iodoalanine methyl ester 
• 108-68-9 3,5-Dimethylphenol 
• 145235-86-5 (S)-4-acetoxy-N-acetyl-2,6-dimethylphenylalanine methyl ester 
• 145235-85-4 methyl (Z)-2-acetamido-3-(4-acetoxy-2,6-dimethylphenyl)-2-propenoate 
• 145235-84-3 4-iodo-3,5-dimethylphenyl acetate 
• 80826-86-4 4-iodo-3,5-dimethylphenol 
• 1333148-31-4 (S)-N-acetyl-2,6-dimethyltyrosine 
• 1255098-61-3 N-acetyl-2,6-dimethyl-DL-tyrosine 

Downstream Products

• 137666-07-0 <2,6-dimethyl-Tyr¹,D-Pen²,D-Pen⁵>enkephalin 
• 848086-40-8 [2-(4-hydroxy-2,6-dimethyl-phenyl)-1-methoxycarbamoyl-ethyl]-carbamic acid tert-butyl ester 
• 848086-41-9 [2-tert-butoxycarbonylamino-3-(4-hydroxy-2,6-dimethyl-phenyl)-propionylamino]-acetic acid tert-butyl ester 
• 848086-34-0 [1-(adamantan-1-ylcarbamoyl)-2-(4-hydroxy-2,6-dimethyl-phenyl)-ethyl]-carbamic acid tert-butyl ester 
• 848086-35-1 [1-(adamantan-2-ylcarbamoyl)-2-(4-hydroxy-2,6-dimethyl-phenyl)-ethyl]-carbamic acid tert-butyl ester 
• 848086-42-0 3-[2-tert-butoxycarbonylamino-3-(4-hydroxy-2,6-dimethyl-phenyl)-propionylamino]-propionic acid tert-butyl ester 
• 848086-43-1 [1-[(tert-butoxycarbonylamino-methyl)-carbamoyl]-2-(4-hydroxy-2,6-dimethyl-phenyl)-ethyl]-carbamic acid tert-butyl ester 
• 848086-33-9 [1-cyclohexylcarbamoyl-2-(4-hydroxy-2,6-dimethyl-phenyl)-ethyl]-carbamic acid tert-butyl ester 
• 848086-38-4 [1-hydroxycarbamoyl-2-(4-hydroxy-2,6-dimethyl-phenyl)-ethyl]-carbamic acid tert-butyl ester 
• 848086-39-5 [2-(4-hydroxy-2,6-dimethyl-phenyl)-1-(2-hydroxy-ethylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester 

Relevant articles and documents

Pd-catalyzed dimethylation of tyrosine-derived picolinamide for synthesis of (S)-N-Boc-2,6-dimethyltyrosine and its analogues

A short and efficient synthesis of (S)-N-Boc-2,6-dimethyltyrosine utilizing palladium-catalyzed directed C-H functionalization is described. This represents the first general method for the ortho-dimethylation of tyrosine derivatives and offers a practical approach for preparing this synthetically important building block. Notably, throughout the reaction sequence no racemization occurs at the susceptible a-chiral centers.

2',6'-dimethyltyrosine derivative and C-H activation methylation synthesis method thereof

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.

N, N - diethyl - carboxylic acid 4 - halomethyl - 3, 5 - dimethyl - phenol ester compound and its preparation method

The invention relates to an N,N-diethyl-formic acid 4-halogenate methyl-3,5-dimethyl-phenol ester compound and a preparing method thereof. The compound is used for synthesis of dimethyl tyrosine. The compound is more effective than compounds involved in t

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).

Development of an asymmetric hydrogenation route to (S)- N -Boc-2,6-dimethyltyrosine

An improved, simpler and potentially more economical route to (S)-N-Boc-2,6-dimethyltyrosine 1, based on a previously published route, is presented. Key modifications were to prepare the dehydroaminoacid hydrogenation substrate 6 in a one-pot process directly from serine methyl ester and 4-iodo-3,5-dimethylphenyl acetate 4 and to identify a significantly more active asymmetric hydrogenation catalyst that allowed a 5-fold reduction in catalyst loading.

Studies on the structure-activity relationship of 2′,6′- dimethyl-l-tyrosine (Dmt) derivatives: Bioactivity profile of H-Dmt-NH-CH 3

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.

Structural studies of [2′,6′-dimethyl-L-tyrosine1]endomorphin-2 analogues: Enhanced activity and cis orientation of the Dmt-Pro amide bond

Analogues of endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH2) (1) were designed to examine the importance of each residue on μ-opioid receptor interaction. Replacement of Tyr1 by 2′,6′-dimethyl-L-tyrosine (Dmt) (9-12) exerted profound effects: [Dmt1]EM-2 (9) elevated μ-opioid affinity 4.6-fold (Kiμ=0.15 nM) yet selectivity fell 330-fold as δ-affinity rose (Kiδ=28.2 nM). This simultaneous increased μ- and δ-receptor bioactivities resulted in dual agonism (IC50=0.07 and 1.87 nM, respectively). While substitution of Phe4 by a phenethyl group (4) decreased μ affinity (Kiμ=13.3 nM), the same derivative containing Dmt (12) was comparable to EM-2 but also acquired weak δ antagonism (pA2=7.05). 1H NMR spectroscopy revealed a trans configuration (1:2 to 1:3, cis/trans) in the Tyr-Pro amide bond, but a cis configuration (5:3 to 13:7, cis/trans) with Dmt-Pro analogues.

Evolution of the Dmt-Tic pharmacophore: N-terminal methylated derivatives with extraordinary δ opioid antagonist activity

The δ opioid antagonist H-Dmt-Tic-OH (2',6'-dimethyl-L-tyrosyl-1,2,3,4- tetrahydroisoquinoline-3-carboxylic acid) exhibits extraordinary δ receptor binding characteristics [K(i)(δ) = 0.022 nM; K(i)(μ)/K(i)(δ) = 150 000] and δ antagonism (pA2 = 8.2; Ke = 5.7 nM). A change in chirality of Dmt at Cα (1, 2, 6, 8, 10, 13) curtailed δ receptor parameters, while replacement of its α-amino function by a methyl group (3) led to inactivity; Tyr-Tic analogues 4 and 11 weakly interacted with δ receptors. N-Alkylation of H- Dmt-Tic-OH and H-Dmt-Tic-Ala-OH with methyl groups produced potent δ-opioid ligands with high δ receptor binding capabilities and enhanced δ antagonism: (i) N-Me-Dmt-Tic-OH 5 had high δ opioid binding (K(i)(δ) = 0.2 nM), elevated δ antagonism on mouse vas deferens (MVD) (pA2 = 8.5; K(e) = 2.8 nM), and nondetectable μ activity with guinea pig ileum (GPI). (ii) N,N- Me2-Dmt-Tic-OH (12) was equally efficacious in δ receptor binding (K(i)(δ) = 0.12 nM; K(i)(μ)/K(i)(δ) = 20 000), but δ antagonism rose considerably (pA2 = 9.4; K(e) = 0.28 nM) with weak μ antagonism (pA2 = 5.8; K(e) = 1.58 μM; GPI/MVD = 1:5640). N-Me-(9) and N,N-Me2-Dmt-Tic-Ala-OH (15) also augmented δ opioid receptor binding, such that 15 demonstrated high affinity (K(i)(δ) = 0.0755 nM) and selectivity (K(i)(μ)/K(i)(δ) = 20 132) with exceptional antagonist activity on MVD (pA2 = 9.6; K(e) = 0.22 nM) and weak antagonism on GPI (pA2 = 5.8; K(e) = 1.58 μM; GPI/MVD = 1:7180). Although the amidated dimethylated dipeptide analogue 14 had high K(i)(δ) (0.31 nM) and excellent antagonist activity (pA2 = 9.9; K(e) = 0.12 nM), the increased activity toward μ receptors in the absence of a free acid function at the C- terminus revealed modest δ selectivity (K(i)(μ)/KK(i)(δ) = 1 655) and somewhat comparable bioactivity (GPI/MVD = 4500). Thus, the data demonstrate that N,N-(Me)2-Dmt-Tic-OH (12) and N,NMe2-Dmt-Tic-Ala-OH (15) retained high δ receptor affinities and δ selectivities and acquired enhanced potency in pharmacological bioassays on MVD greater than that of other peptide or non- peptide δ antagonists.

Process for producing 2,6-disubstituted tyrosine

A process for making 2,6-disubstituted tyrosine by the noble metal coupling of a disubstituted aromatic halide or diazonium salt with an amino-protected 2-aminoacrylic acid to form a (Z)-β-(disubstituted phenyl)-α-acylaminoacrylate, and asymmetrically hydrogenating the acrylate to produce the 2,6-disubstituted tyrosine.