300-39-0

Basic information

• Product Name: 3,5-Diiodo-L-tyrosine dihydrate
• Synonyms: 3,5-Diiodo-4-hydroxy-β-phenylalanine;3,5-diiodo-l-tyrosin;3,5-Diiodotyrocine;3,5-Iodo-L-tyrosine;3,5-L-Diiodotyrosine;4-Hydroxy-3,5-diiodophenylalanine;diiodotyrosine;L-3,5-DiioDOTyrosine
• CAS NO: 300-39-0
• Molecular Formula: C9H13I2NO5
• Molecular Weight: 469.01
• EINECS: 206-092-0
• Product Categories: Pharmaceutical Raw Materials;Amino Acids;Unusual Amino Acids;Biochemistry;Biological-modified Amino Acids
• Mol File: 300-39-0.mol
• Article Data: 7

Chemical Properties

• Melting Point: 200 °C (dec.)(lit.)
• Boiling Point: 546.5°C (rough estimate)
• Flash Point: 202.1 °C
• Appearance: white/crystalline
• Density: 2.405 g/cm³
• Vapor Pressure: 1.78E-07mmHg at 25°C
• Refractive Index: 1.2 ° (C=5, 1mol/L HCl)
• Storage Temp.: 2-8°C
• Solubility: Aqueous Acid (Slightly), DMSO (Slightly)
• PKA: 2.12(at 25℃)
• Water Solubility: slightly soluble
• Sensitive: Light Sensitive
• CAS DataBase Reference: 3,5-Diiodo-L-tyrosine dihydrate(CAS DataBase Reference)
• NIST Chemistry Reference: 3,5-Diiodo-L-tyrosine dihydrate(300-39-0)
• EPA Substance Registry System: 3,5-Diiodo-L-tyrosine dihydrate(300-39-0)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-37/39-36/37-24/25
• RIDADR: 2811
• WGK Germany: 3
• F: 8
• TSCA: Yes
• Hazardous Substances Data: 300-39-0(Hazardous Substances Data)

Usage

Description

Diiodotyrosine does not possess pronounced hormonal activity. However, it stops production of thyrotropic hormone by the anterior lobe of the hypophysis, which activates thyroid gland activity.

Chemical Properties

white to beige powder

Uses

Different sources of media describe the Uses of 300-39-0 differently. You can refer to the following data:
1. It is used for hyperthyroid forms of endemic and sporadic goiters, diffuse, toxic goiters, and other illnesses accompanied by thyrotoxicity.
2. 3,5-Diiodo-L-tyrosine is a reactant used in the synthesis of fluorescent unnatural amino acids bearing stilbene or vinylene backbones. Also used in the discovery of potent heterodimeric antagonists of inhibitor of Apoptosis proteins with prolonged anti-tumor activity.

Definition

ChEBI: A diiodotyrosine that is L-tyrosine carrying iodo-substituents at positions C-3 and C-5 of the benzyl group. It is an intermediate in the thyroid hormone synthesis.

Synthesis

Diiodotyrosine, 3,5-diiodotyrosine (25.2.1), is synthesized by directly iodinating tyrosine with iodine in the presence of sodium iodide in aqueous ethylamine, or in a mixture of acetic and hydrochloric acids with the addition of hydrogen peroxide.

Purification Methods

It forms crystals from H2O [solubility (g/L): 0.204 at 0o, 1.86 at 50o, 5.6 at 75o and 17.0 at 100o]. Also recrystallise it from 50% or 70% EtOH. When boiled in EtOH the crystals swell, and on further boiling a gelatinous precipitate is formed [Harrington Biochem J 22 1434 1928, Jurd J Am Chem Soc 77 5747 1955]. It also crystallises from cold dilute ammonia on adding acetic acid to pH 6. [Beilstein 14 IV 2370.]

InChI:InChI=1/C9H9I2NO3/c10-5-1-4(2-6(11)8(5)13)3-7(12)9(14)15/h1-2,7,13H,3,12H2,(H,14,15)

Synthetic route

L-tyrosine (60-18-4) → 3,5-diiodo-l-tyrosine (300-39-0)

Conditions	Yield
With hydrogen iodide; acetic acid In dimethyl sulfoxide at 65℃; for 0.025h;	84.63%
With iodine; ethylamine; sodium iodide In water for 0.666667h;	73.5%
With ammonium hydroxide; iodine; potassium iodide

L-tyrosine (60-18-4) → 3,5-diiodo-l-tyrosine (300-39-0) + 3-Iodo-L-tyrosine (70-78-0)

Conditions	Yield
With chloroamine-T; sodium iodide In water at 20℃; for 0.00277778h; Product distribution; other reaction time, pregenerated iodine, reaction in the presence of tryptophan and Nin-formyl-tryptophan;	A 38.6% B 32.6%
With iodide; dihydrogen peroxide; lactoperoxidase

3-Iodo-L-tyrosine (70-78-0) → 3,5-diiodo-l-tyrosine (300-39-0)

Conditions	Yield
With iodine In water at 22℃; for 0.0833333h; potassim iodide/chloramine T in phosphate buffer instead of iodine; tritium isotope effect;

ammonia (7664-41-7) + iodine (7553-56-2) + L-tyrosine (60-18-4) → 3,5-diiodo-l-tyrosine (300-39-0)

methanol (67-56-1) + 3,5-diiodo-l-tyrosine (300-39-0) → 3,5-diiodo-L-thyrosine methyl ester (76318-50-8)

Conditions	Yield
With sulfuryl dichloride at 0 - 20℃; Inert atmosphere;	100%
With hydrogenchloride at 60℃; for 0.0416667h; Microwave irradiation;	74.63%
With hydrogenchloride
With thionyl chloride

Boc-Val-ONSu (3392-12-9) + 3,5-diiodo-l-tyrosine (300-39-0) → (S)-2-((S)-2-tert-Butoxycarbonylamino-3-methyl-butyrylamino)-3-(4-hydroxy-3,5-diiodo-phenyl)-propionic acid

Conditions	Yield
With triethylamine In tetrahydrofuran; water at 20℃; Condensation;	100%

3,5-diiodo-l-tyrosine (300-39-0) + copper(II) sulfate (7758-99-8) → 3,5-diiodo L-tyrosine copper complex

Conditions	Yield
Stage #1: 3,5-diiodo-l-tyrosine With sodium hydroxide In water for 1h; Stage #2: copper(II) sulfate In water at 20 - 40℃; for 2h;	98%

methanol (67-56-1) + 3,5-diiodo-l-tyrosine (300-39-0) → 3,5-diiodo-L-tyrosine methyl ester hydrochloride (151266-48-7)

Conditions	Yield
Stage #1: methanol With thionyl chloride at 0℃; for 0.166667h; Inert atmosphere; Stage #2: 3,5-diiodo-l-tyrosine at 20℃; for 16h;	98%

3,5-diiodo-l-tyrosine (300-39-0) + 5,7-diiodo-1-oxaspiro[2.5]octa-4,7-dien-6-one → L-thyroxine (51-48-9)

Conditions	Yield
In N,N-dimethyl-formamide at 24℃; for 16h; 0.2 M borate buffer, pH 8.0 (add. of 0.1 M NaOH);	94%

copper(II) sulfate heptahydrate + 3,5-diiodo-l-tyrosine (300-39-0) → {Cu(HOC6H2I2CH2CH(NH2)COO)2} (49553-16-4)

Conditions	Yield
With sodium hydroxide In water at 20℃; for 1h; Time;	93.7%

3,5-diiodo-l-tyrosine (300-39-0) + acetic anhydride (108-24-7) → N-acetyl-3,5-diiodo-L-tyrosine (1027-28-7)

Conditions	Yield
With sodium hydroxide In water at 0 - 15℃;	92%
With sodium hydroxide

di-tert-butyl dicarbonate (24424-99-5) + 3,5-diiodo-l-tyrosine (300-39-0) → C14H19I2NO4

Conditions	Yield
Stage #1: 3,5-diiodo-l-tyrosine With chloro-trimethyl-silane In 1,4-dioxane for 48h; Stage #2: di-tert-butyl dicarbonate With sodium hydroxide In tetrahydrofuran; water at 0 - 20℃;	79%

formaldehyd (50-00-0) + 3,5-diiodo-l-tyrosine (300-39-0) → (S)-7-hydroxy-6,8-diiodo-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid hydrochloride

Conditions	Yield
With hydrogenchloride In 1,2-dimethoxyethane; water at 72℃; for 4h;	72%
With hydrogenchloride In 1,2-dimethoxyethane; water at 72℃; Inert atmosphere;	72%
With hydrogenchloride In 1,2-dimethoxyethane; water at 72℃; Inert atmosphere;	72%

3,5-diiodo-l-tyrosine (300-39-0) + 5-Iodo-1-oxa-spiro[2.5]octa-4,7-dien-6-one → triiodothyronine (6893-02-3)

Conditions	Yield
In N,N-dimethyl-formamide at 24℃; for 16h; 0.2 M borate buffer, pH 8.0 (add. of 0.1 M NaOH);	70%

methanol (67-56-1) + di-tert-butyl dicarbonate (24424-99-5) + 3,5-diiodo-l-tyrosine (300-39-0) → (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(4-hydroxy-3,5-diiodophenyl)propanoate (128781-80-6)

Conditions	Yield
Stage #1: methanol; 3,5-diiodo-l-tyrosine With thionyl chloride at 0℃; for 2h; Reflux; Stage #2: With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; Stage #3: di-tert-butyl dicarbonate In dichloromethane at 20℃;	64%
With thionyl chloride; triethylamine 1.) -10 deg C - room temperature, 2.) CH2Cl2; Yield given. Multistep reaction;

cis-dichloridobis(1,10-phenanthroline)ruthenium(II) + 3,5-diiodo-l-tyrosine (300-39-0) + sodium perchlorate → Ru(N2C12H8)2(NH2CHCH2C6H2I2OHCOO)(1+)*NH2CHCH2C6H2I2OHCOO(1-)=Ru(N2C12H8)2(NH2CHCH2C6H2I2OHCOO)(NH2CHCH2C6H2I2OHCOO)

Conditions

Yield

With sodium hydroxide In ethanol; water Ru-complex was refluxed in mixt. of H2O and EtOH, to this soln. was added ligand followed by aq. NaOH, mixt. was heated at 70°C for 30 min, cooled to room temp., filtered, cooled to room temp., aq. soln. of NaClO4 was added; mixt. was stored in the dark for 48 h, solid was collected at the pump,washed with ice-cold H2O, dried in vac. over silica gel at room temp.; elem. anal.;

64%

formaldehyd (50-00-0) + 3,5-diiodo-l-tyrosine (300-39-0) → (S)-1,2,3,4-Tetrahydro-7-hydroxy-6,8-diiodoisoquinoline-3-carboxylic acid (142335-40-8)

Conditions	Yield
With hydrogenchloride In 1,2-dimethoxyethane; water at 72℃; for 18.5h;	57%
With hydrogenchloride In 1,2-dimethoxyethane at 72℃; for 18.5h;	55%
With hydrogenchloride In 1,2-dimethoxyethane at 72℃; for 18.5h;	48%

indan-1,2,3-trione hydrate (485-47-2) + 3,5-diiodo-l-tyrosine (300-39-0) + 1,2,3-triphenylcyclopropene (16510-49-9) → (±)-(1R,4R,5S,6R)-4-(4-hydroxy-3,5-diiodobenzyl)-1,5,6-triphenyl-3-azaspiro[bicyclo[3.1.0]hexane-2,2'-indene]-1',3'-dione

Conditions	Yield
In methanol; water for 10h; Reflux; diastereoselective reaction;	57%

N-(tert-butyloxycarbonyl) azide (1070-19-5) + 3,5-diiodo-l-tyrosine (300-39-0) → (tert-butoxycarbonyl)-3,5-diiodotyrosine (62129-53-7)

Conditions	Yield
In dimethyl sulfoxide Ambient temperature;	50%

3,5-diiodo-l-tyrosine (300-39-0) + methyl iodide (74-88-4) → (E)-methyl 3-(3,5-diiodo-4-methoxyphenyl)acrylate + L-3,5-diiodo-O-methyltyrosine methyl ester + L-3,5-diiodo-O,N,N-trimethyltyrosine methyl ester

Conditions	Yield
With potassium carbonate In acetone for 24h; Heating;	A 50% B 20% C 20%

3,5-diiodo-l-tyrosine (300-39-0) + indole-2,3-dione (91-56-5) + 1,2,3-triphenylcyclopropene (16510-49-9) → (±)-(1R,2R,4R,5S,6R)-4-(4-hydroxy-3,5-diiodobenzyl)-1,5,6-triphenyl-3-azaspiro[bicyclo[3.1.0]hexane-2,3′-indolin]-2′-one

Conditions	Yield
In methanol; water Reflux; diastereoselective reaction;	42%

1-oxaspiro[2.5]octa-4,7-dien-6-one (54337-43-8) + 3,5-diiodo-l-tyrosine (300-39-0) → 3,5-diiodo-L-thyronine (1041-01-6, 534-51-0, 5563-89-3, 299-82-1)

Conditions	Yield
In N,N-dimethyl-formamide at 24℃; for 16h; 0.2 M borate buffer, pH 8.0 (add. of 0.1 M NaOH);	15%

ethanol (64-17-5) + 3,5-diiodo-l-tyrosine (300-39-0) → 3,5-diiodo-L-tyrosine ethyl ester (35591-33-4)

Conditions	Yield
With hydrogenchloride

3,5-diiodo-l-tyrosine (300-39-0) → L-thyroxine (51-48-9)

Conditions	Yield
With sodium hydroxide; dihydrogen peroxide; butan-1-ol
Multi-step reaction with 4 steps 1.1: sodium hydroxide / water / 1 h 1.2: 2 h / 20 - 40 °C 2.1: diisopropylamine / water; butan-1-ol / 2 h / 20 - 90 °C 2.2: 2 h / 20 - 30 °C 3.1: acetic acid; hydrogen iodide / 5 h / 100 °C 4.1: methylamine / methanol / 25 - 30 °C 4.2: -8 - 0 °C 4.3: 15 - 20 °C View Scheme

3,5-diiodo-l-tyrosine (300-39-0) → 4-(4-hydroxy-3,5-diiodo-benzyl)-2-methyl-4H-oxazol-5-one

Conditions	Yield
With acetic anhydride

3,5-diiodo-l-tyrosine (300-39-0) + acetic anhydride (108-24-7) → 3.5-diiodo-N.O-diacetyl-L-tyrosine (96679-34-4)

Conditions	Yield
With sodium hydroxide

3,5-diiodo-l-tyrosine (300-39-0) + acetic anhydride (108-24-7) → N-[1-acetyl-2-(4-hydroxy-3,5-diiodo-phenyl)-ethyl]-acetamide

Conditions	Yield
With sodium carbonate

3,5-diiodo-l-tyrosine (300-39-0) + 2,4-Dinitrofluorobenzene (70-34-8) → N-(2,4-dinitro-phenyl)-3,5-diiodo-L-tyrosine (100961-33-9)

Conditions	Yield
With diethyl ether; sodium hydrogencarbonate

3,5-diiodo-l-tyrosine (300-39-0) + 2,4-Dinitrofluorobenzene (70-34-8) → O-(2,4-dinitro-phenyl)-3,5-diiodo-L-tyrosine

Conditions	Yield
With sodium hydrogencarbonate

3,5-diiodo-l-tyrosine (300-39-0) + 2,4-Dinitrofluorobenzene (70-34-8) → N,O-bis-(2,4-dinitro-phenyl)-3,5-diiodo-L-tyrosine (7093-57-4)

Conditions	Yield
With diethyl ether; sodium hydrogencarbonate

3,5-diiodo-l-tyrosine (300-39-0) + chloroacetyl chloride (79-04-9) → N-chloroacetyl-3,5-diiodo-L-tyrosine (91348-81-1)

Conditions	Yield
With ethyl acetate

3,5-diiodo-l-tyrosine (300-39-0) + butan-1-ol (71-36-3) → 3,5-diiodo-L-tyrosine butyl ester

Conditions	Yield
With hydrogenchloride

Upstream product

• 60-18-4 L-tyrosine 
• 7664-41-7 ammonia 
• 7553-56-2 iodine 
• 70-78-0 3-Iodo-L-tyrosine 

Downstream Products

• 51-48-9 L-thyroxine 
• 105245-16-7 N-methacryloyl methacryloyloxy-4 diiodo-3,5-L-phenylalanine 
• 109921-21-3 (S)-2-((S)-2-tert-Butoxycarbonylamino-3-phenyl-propionylamino)-3-(4-hydroxy-3,5-diiodo-phenyl)-propionic acid 
• 60-18-4 L-tyrosine 
• 174592-01-9 N-benzyloxycarbonyl-3,5-diiodo-L-tyrosine 
• 113850-74-1 methyl (S)-2-((tert-butoxycarbonyl)amino)-3-(3,5-diiodo-4-methoxyphenyl)propanoate 
• 1423720-70-0 (S)-tert-butyl 1-(3,5-diiodo-4-methoxyphenyl)-3-hydroxypropan-2-ylcarbamate 
• 1426447-00-8 (S)-tert-butyl 1-(3,5-diiodo-4-methoxyphenyl)-3-(methoxymethoxy)propan-2-ylcarbamate 
• 1426447-03-1 C₁₇H₂₇NO₇ 
• 1426447-04-2 C₁₇H₂₇NO₆ 
• 914955-59-2 (S)-2-Benzyloxycarbonylamino-3-(4-hydroxy-3,5-bis-hydroxymethyl-phenyl)-propionic acid 
• 1426446-98-1 C₂₁H₂₅NO₇ 
• 1426446-97-0 C₂₁H₂₁NO₇ 
• 1164-16-5 Z-L-Tyr-OH 

Relevant articles and documents

Interaction of anti-thyroid drugs with iodine: The isolation of two unusual ionic compounds derived from Se-methimazole

The inhibition of lactoperoxidase (LPO)-catalyzed iodination of l-tyrosine by the anti-thyroid drug methimazole (MMI) and its selenium analogue (MSeI) is described. MSeI inhibits LPO with an IC50 value of 12.4 M, and this inhibition could be completely reversed by increasing the peroxide concentration. In addition to the inhibition, MSeI reacts with molecular iodine to produce novel ionic diselenides, and the nature of the species formed in this reaction appear to be solvent-dependent. The formation of ionic species in the reaction is confirmed by single-crystal X-ray studies, FT-IR and FT-Raman spectroscopic investigations. This study provides the first experimental evidence that MSeI not only effectively inhibits the LPO-catalyzed iodination of tyrosine, but also reacts with I2 to produce novel ionic diselenides. These results also suggest that MSeI reacts with iodine, even in its oxidized form, to form ionic diselenides containing iodide or polyiodide anions, which might be effective intermediates in the inhibition of thyroid hormones. The Royal Society of Chemistry 2006.

An efficient synthesis of l-3,4,5-trioxygenated phenylalanine compounds from l-tyrosine

A new strategy for the synthesis of l-3,4,5-trioxygenated phenylalanine derivatives from l-tyrosine is developed for the first time. The approach, featuring the transformation of aryl diiodide to bis-phenol via a one-pot procedure including lithiation, boronation, and oxidation, is highly practical. By this robust protocol, N-protected l-3,5-bis(tert-butyldimethylsilyloxy)-4- methoxy-phenylalanine and l-3,4,5-trimethoxy-phenylalanine derivatives were obtained from l-tyrosine in 9 steps with 36-40% overall yields.

First aromatic electrophilic iodination reaction on the solid-phase: Iodination of bioactive peptides

Direct iodination of Tyr residues of peptides anchored on solid supports was accomplished, for the first time, by aromatic electrophilic attack of iodonium ions provided by the IPy2BF4 reagent. Compatibility studies of the iodination with routine solid-phase synthesis protocols are reported.