3-IODO-L-TYROSINE

3-IODO-L-TYROSINE Property

Melting point:

210 °C (dec.)(lit.)

Density 

1.7280 (estimate)

storage temp. 

-20°C

solubility 

dilute aqueous acid: soluble

form 

Solid

Boiling point:

391.0±42.0 °C(Predicted)

pka

2.21±0.20(Predicted)

color 

White to off-white

Sensitive 

Light Sensitive

Merck 

14,5047

BRN 

2941266

Stability:

Hygroscopic

InChIKey

UQTZMGFTRHFAAM-ZETCQYMHSA-N

CAS DataBase Reference

70-78-0(CAS DataBase Reference)

EPA Substance Registry System

L-Tyrosine, 3-iodo- (70-78-0)

Safety

Safety Statements 

24/25

WGK Germany 

3

F 

8-10-23

HS Code 

29225090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H314Causes severe skin burns and eye damage

Precautionary statements

P280Wear protective gloves/protective clothing/eye protection/face protection.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P310Immediately call a POISON CENTER or doctor/physician.

3-IODO-L-TYROSINE Chemical Properties,Usage,Production

Chemical Properties

White Solid

Uses

A novel flavoprotein responsible for iodide salvage in thyroid glands. A tyrosine hydroxylase inhibitor.

Uses

3-iodo-l-tyrosine is used in the inhibition of tyrosine hydroxylase. 3-iodo-L-tyrosine is used in the rapid induction of prolactin secretion.

Uses

3-Iodo-L-tyrosine has been used as an inhibitor for tyrosine hydroxylase enzyme in Drosophila and silkworm pupae.

Definition

ChEBI: The monoiodotyrosine that is L-tyrosine carrying an iodo-substituent at position C-3 of the benzyl group.

General Description

Iodotyrosine coupled with di-iodotyrosine results in the synthesis of 3,5,3′-tri-iodothyronine (T3) or 3,3′,5′-tri-iodothyronine (rT3).

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.

Synthesis

General procedure for the synthesis of (S)-2-amino-3-(4-hydroxy-3-iodophenyl)propionic acid from L-tyrosine: L-tyrosine (147.3 kg, 813 mol, 1 eq.) and concentrated hydrochloric acid were added to a 3000 L reactor. Ammonia (25%, 1980kg, 13.5w) was then added to form a white suspension. The suspension was cooled to -10 to 0°C. At this temperature, iodine (223 kg, 878 mol, 1.08 eq.) was added in 40 batches, taking about 5 hours. After addition, stirring was continued at -10 to 0 °C for about 2 hours. Samples were diluted with water and analyzed by HPLC, which showed 86.4% of A7 (target product), 11.3% of diiodide and 2.3% of unreacted L-tyrosine. Subsequently, the reaction solution was concentrated under vacuum at 0 to 40 °C for 28 h until the pH of the residue was reduced to 9.6. The concentrated solution was cooled to 20-30 °C, at which temperature the pH was adjusted to 8 by dropwise addition of an aqueous 18% hydrochloric acid solution, taking about 10 h. The reaction solution was then concentrated in a vacuum at 0 to 40 °C for about 1 h. The reaction solution was then concentrated at 0 to 40 °C for about 1 h. The reaction solution was then concentrated in a vacuum at 0 to 40 °C for about 1 h. A7 (0.25 kg) was added as a crystal seed and stirring was continued at 20-30 °C for about 1 hour. Subsequently, the pH of the mixture was continuously adjusted to 7.4 with 18% aqueous hydrochloric acid solution over a period of 3 hours and stirred for 1 hour at each pH stage. Finally, stirring was continued for 2 hours at 20-30°C (in total, about 1200 kg of 18% aqueous hydrochloric acid solution was used for crystallization). The slurry was centrifuged and the wet filter cake was washed twice each with water (230 kg, 1.6 w, each time) and acetone (230 kg, 1.6 w, each time) sequentially. The solid was dried under vacuum at 50-60 °C for about 48 h to give A7 (156.6 kg) with a purity of 96% and a water content of 2.5% as a light brown solid in a yield of 62.6% (uncorrected; after deduction of 0.25 kg of A7 crystalline seed).

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.]

References

[1] Journal of Labelled Compounds and Radiopharmaceuticals, 1998, vol. 41, # 4, p. 255 - 259
[2] Chemistry - A European Journal, 2010, vol. 16, # 34, p. 10523 - 10534
[3] Patent: WO2018/183198, 2018, A1. Location in patent: Page/Page column 32; 36-38
[4] Organic Letters, 2012, vol. 14, # 9, p. 2402 - 2405
[5] Journal of Medicinal Chemistry, 2018, vol. 61, # 8, p. 3350 - 3369