70-78-0

Basic information

• Product Name: 3-IODO-L-TYROSINE
• Synonyms: 3-Iodo-4-hydroxyphenylalanine;4-Hydroxy-3-iodophenylalanine;3-iodine-L- tyrosine;3-I-L-Tyr-OH;3-Iodo-L-tyrosine≥ 98% (HPLC);H-L-Phe(3-I,4-OH)-OH;L-TYROSINE, 3-IODO-;H-TYR(M-I)-OH
• CAS NO: 70-78-0
• Molecular Formula: C₉H₁₀INO₃
• Molecular Weight: 307.09
• EINECS: 200-744-8
• Product Categories: amino;Unusual Amino Acids;Amino Acids 13C, 2H, 15N;Amino Acids;Biochemistry;Biological-modified Amino Acids;Amino Acids & Derivatives;Inhibitors;Aromatics;Chiral Reagents
• Mol File: 70-78-0.mol

Chemical Properties

• Melting Point: 210 °C (dec.)(lit.)
• Boiling Point: 390.969 °C at 760 mmHg
• Flash Point: 190.251 °C
• Appearance: White to off-white/Solid
• Density: 1.7280 (estimate)
• Vapor Pressure: 8.18E-07mmHg at 25°C
• Refractive Index: 1.688
• Storage Temp.: 2-8°C
• Solubility: dilute aqueous acid: soluble
• PKA: 2.21±0.20(Predicted)
• Sensitive: Light Sensitive
• Stability: Hygroscopic
• Merck: 14,5047
• BRN: 2941266
• CAS DataBase Reference: 3-IODO-L-TYROSINE(CAS DataBase Reference)
• NIST Chemistry Reference: 3-IODO-L-TYROSINE(70-78-0)
• EPA Substance Registry System: 3-IODO-L-TYROSINE(70-78-0)

Safety Data

• Safety Statements: 24/25
• WGK Germany: 3
• F: 8-10-23
• Hazardous Substances Data: 70-78-0(Hazardous Substances Data)

Usage

Uses

Used in Thyroid Hormone Synthesis:
3-IODO-L-TYROSINE is used as a precursor in the synthesis of thyroid hormones for maintaining normal metabolic function and growth in the human body.
Used in Pharmaceutical Applications:
3-IODO-L-TYROSINE is used as a tyrosine hydroxylase inhibitor for its potential role in the treatment of various neurological and psychiatric disorders.
Used in Inhibition of Tyrosine Hydroxylase:
3-IODO-L-TYROSINE is used as an inhibitor for the tyrosine hydroxylase enzyme in Drosophila and silkworm pupae, which can be useful in studying the enzyme's function and its role in various biological processes.
Used in Rapid Induction of Prolactin Secretion:
3-IODO-L-TYROSINE is used in the rapid induction of prolactin secretion, which can have implications in the study and treatment of reproductive and lactation-related conditions.
Used in Iodide Salvage in Thyroid Glands:
3-IODO-L-TYROSINE is used as a novel flavoprotein responsible for iodide salvage in thyroid glands, which is essential for the proper functioning of the thyroid and the production of thyroid hormones.

Biochem/physiol Actions

3-iodotyrosine (3-IY) inhibits tyrosine hydroxylase that catalyzes levodopa (L-DOPA) formation from tyrosine. Iodotyrosine deiodinase enzyme deficiency leads to elevated levels of 3-IY in serum and urine in severe hypothyroidism and goiter.

Purification Methods

Likely impurities are tyrosine, diiodotyrosine and iodide. Crystallise it by dissolving it in concentrated ammonia (~200mg in ~20mL), evaporate to ~5mL and NH4Cl is added to pH4.5—5.0. After a few hours at 0o, the amino acid crystallises in needles. It is filtered off, washed with a little ice-cold H2O and dried in a vacuum. Alternatively dissolve it in dilute ammonia at room temperature, then add dilute acetic acid to pH 6. Store it at 0o. Recrystallisation of ~250mg from H2O (~5mL) removes any diiodotyrosine. It is an inhibitor of tyrosine hydroxylase with a Ki of ~500nM. [Harrington & Rivers Biochem J 38 320 1944, Rivers Chem & Ind (London) 21 1956, Beilstein 14 III 1562, 14 IV 1562.]

InChI:InChI=1/C9H10INO3/c10-6-3-5(1-2-8(6)12)4-7(11)9(13)14/h1-3,7,12H,4,11H2,(H,13,14)/t7-/m1/s1

Upstream product

• 29588-94-1 N-phthaloyl-L-tyrosine 
• 60-18-4 L-tyrosine 
• 300-39-0 3,5-diiodo-l-tyrosine 
• 79677-58-0 2-amino-3-(3-iodo-4-hydroxyphenyl)propionic acid methyl ester hydrochloride 

Downstream Products

• 54709-23-8 3,4-dihydroxy-5-iodo-L-phenylalanine 
• 79677-58-0 2-amino-3-(3-iodo-4-hydroxyphenyl)propionic acid methyl ester hydrochloride 
• 70277-02-0 3-iodo-L-tyrosine methyl ester 
• 79677-62-6 (S)-2-(((benzyloxy)carbonyl)amino)-3-(4-hydroxy-3-iodophenyl)propanoic acid 
• 300-39-0 3,5-diiodo-l-tyrosine 
• 130934-38-2 3-iodotyrosine phenoxyl radical 
• 60-18-4 L-tyrosine 
• 71400-63-0 N-tert-butyloxycarbonyl-3-iodo-L-tyrosine 
• 71400-62-9 O^4'-Benzyl-3'-iod-L-tyrosin 
• 113850-71-8 (S )-methyl 2-((tert-butoxycarbonyl)amino)-3-(3-iodo-4-methoxyphenyl)propanoate 
• 134486-00-3 (S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-(4-hydroxy-3-iodophenyl)propionic acid 
• 930273-90-8 2-tert-butoxycarbonylamino-3-(4-methoxy-3-vinyl-phenyl)-propionic acid methyl ester 
• 926292-85-5 2-tert-butoxycarbonylamino-3-[3-(2-hydroxy-ethyl)-4-methoxy-phenyl]-propionic acid methyl ester 
• 926292-80-0 2-tert-butoxycarbonylamino-3-(4-methoxymethoxy-3-vinyl-phenyl)-propionic acid methyl ester 

Relevant articles and documents

Inhibition of thyroid peroxidase by dietary flavonoids

Flavonoids are widely distributed in plant-derived foods and possess a variety of biological activities including antithyroid effects in experimental animals and humans. A structure-activity study of 13 commonly consumed flavonoids was conducted to evaluate inhibition of thyroid peroxidase (TPO), the enzyme that catalyzes thyroid hormone biosynthesis. Most flavonoids tested were potent inhibitors of TPO, with IC50 values ranging from 0.6 to 41 μM. Inhibition by the more potent compounds, fisetin, kaempferol, naringenin, and quercetin, which contain a resorcinol moiety, was consistent with mechanism-based inactivation of TPO as previously observed for resorcinol and derivatives. Other flavonoids inhibited TPO by different mechanisms, such as myricetin and naringin, showed noncompetitive inhibition of tyrosine iodination with respect to iodine ion and linear mixed-type inhibition with respect to hydrogen peroxide. In contrast, biochanin A was found to be an alternate substrate for iodination. The major product, 6,8- diiodo-biochanin A, was characterized by electrospray mass spectrometry and 1H-NMR. These inhibitory mechanisms for flavonoids are consistent with the antithyroid effects observed in experimental animals and, further, predict differences in hazards for antithyroid effects in humans consuming dietary flavonoids. In vivo, suicide substrate inhibition, which could be reversed only by de novo protein synthesis, would be long-lasting. However, the effects of reversible binding inhibitors and alternate substrates would be temporary due to attenuation by metabolism and excretion. The central role of hormonal regulation in growth and proliferation of thyroid tissue suggests that chronic consumption of flavonoids, especially suicide substrates, could play a role in the etiology of thyroid cancer.

Synthesis of the Rubiyunnanin B Core Aglycon

Rubiyunnanin B possesses an intriguing anticancer profile whose activity is dependent on the glycosylation of a fused tyrosinyl residue. We have developed a rapid synthesis of the rubiyunnanin B dityrosine core using a Suzuki coupling. Furthermore, the atropisomeric and isomeric products obtained were identified and their distribution controlled. The two major products obtained from the dityrosine coupling were discovered to be locked cis/trans isomers of the internal amide with atropisomerization quantifiable on the NMR timescale.

Stereocontrolled Synthesis of Arylomycin-Based Gram-Negative Antibiotic GDC-5338

We report herein an efficient, stereocontrolled, and chromatography-free synthesis of the novel broad spectrum antibiotic GDC-5338. The route features the construction of a functionalized tripeptide backbone, a high-yielding macrocyclization via a Pd-catalyzed Suzuki-Miyaura reaction, and the late-stage elaboration of key amide bonds with minimal stereochemical erosion. Through extensive reaction development and analytical understanding, these key advancements allowed the preparation of GDC-5338 in 17 steps, 15% overall yield, >99 A % HPLC, and >99:1 dr.

PROCESS FOR MAKING ARYLOMYIN RING ANALOGS

Methods for making an arylomycin ring of formula t or salts or solvates thereof, wherein R, R1, R2, R3, R4, R5, R6, R7, R8, R9, R5, R10 and Pg1 are as defined herein.

Repurposing a Library of Human Cathepsin L Ligands: Identification of Macrocyclic Lactams as Potent Rhodesain and Trypanosoma brucei Inhibitors

Rhodesain (RD) is a parasitic, human cathepsin L (hCatL) like cysteine protease produced by Trypanosoma brucei (T. b.) species and a potential drug target for the treatment of human African trypanosomiasis (HAT). A library of hCatL inhibitors was screened, and macrocyclic lactams were identified as potent RD inhibitors (Ki 50 400 nM). SARs addressing the S2 and S3 pockets of RD were established. Three cocrystal structures with RD revealed a noncovalent binding mode of this ligand class due to oxidation of the catalytic Cys25 to a sulfenic acid (Cys-SOH) during crystallization. The P-glycoprotein efflux ratio was measured and the in vivo brain penetration in rats determined. When tested in vivo in acute HAT model, the compounds permitted up to 16.25 (vs 13.0 for untreated controls) mean days of survival.

Remarkable Effect of Chalcogen Substitution on an Enzyme Mimetic for Deiodination of Thyroid Hormones

Iodothyronine deiodinases are selenoenzymes which regulate the thyroid hormone homeostasis by catalyzing the regioselective deiodination of thyroxine (T4). Synthetic deiodinase mimetics are important not only to understand the mechanism of enzyme catalysis, but also to develop therapeutic agents as abnormal thyroid hormone levels have implications in different diseases, such as hypoxia, myocardial infarction, critical illness, neuronal ischemia, tissue injury, and cancer. Described herein is that the replacement of sulfur/selenium atoms in a series of deiodinase mimetics by tellurium remarkably alters the reactivity as well as regioselectivity toward T4. The tellurium compounds reported in this paper represent the first examples of deiodinase mimetics which mediate sequential deiodination of T4 to produce all the hormone derivatives including T0 under physiologically relevant conditions.

Total synthesis of mycocyclosin

The first total synthesis of mycocyclosin, a diketopiperazine natural product isolated from M. tuberculosis, is described. While direct oxidative coupling of tyrosine phenolic groups was unsuccessful, construction of the highly strained bicyclic framework was successfully accomplished through an intramolecular Miyaura-Suzuki cross-coupling to generate the biaryl linkage.

Proton-coupled electron transfer from tyrosine: A strong rate dependence on intramolecular proton transfer distance

Proton-coupled electron transfer (PCET) was examined in a series of biomimetic, covalently linked RuII(bpy)3-tyrosine complexes where the phenolic proton was H-bonded to an internal base (a benzimidazyl or pyridyl group). Photooxidation in laser flash/quench experiments generated the RuIII species, which triggered long-range electron transfer from the tyrosine group concerted with short-range proton transfer to the base. The results give an experimental demonstration of the strong dependence of the rate constant and kinetic isotope effect for this intramolecular PCET reaction on the effective proton transfer distance, as reflected by the experimentally determined proton donor-acceptor distance.

Intramolecular suzuki-miyaura reaction for the total synthesis of signal peptidase inhibitors, arylomycins A2and B2

Development of the total syntheses of arylomycins A1 and B 2 is detailed. Key features of our approach include 1) formation of 14-membered meta, meta-cyclophane by an intramolecular Suzuki-Miyaura reaction; 2) incorporation of N-Me-4-hydroxyphenylglycine into the cyclization precursor, which avoids the late-stage low-yielding N-methylation step; 3) segment coupling of a fully elaborated peptide side chain to the macrocycle, which makes the synthesis highly convergent. Overall, arylomycin A2 was obtained in 13 steps from L-Tyr for the longest linear sequence, in 13% overall yield. Arylomycin B2 was synthesized in 10 steps from L-3-nitro-Tyr, in 10% overall yield.

Thieme Chemistry Journal awardees - Where are they now? Scope of tyrosine O-arylations with boronic acids: Optimized synthesis of an orthogonally protected isodityrosine

The Evans-Chan-Lam variant of the Ullman condensation has been explored to deliver O-arylated tyrosines and tyrosinyl peptides. Key modifications for success were the slow addition of boronic acids to the phenol-catalyst mixture. Selectivity and scope are investigated. Georg Thieme Verlag Stuttgart.