5817-39-0

Basic information

• Product Name: REVERSE T3
• Synonyms: REVERSE T3;T3;LIOTHYRONIN;L-3,3',5'-TRIIODOTHYRONINE;(3,5,3')-TRIIODO-L-THYRONINE;Reverse T3;3,3',5'-triiodo-L-thyronine free acid;Isoliothyronine
• CAS NO: 5817-39-0
• Molecular Formula: C₁₅H₁₂I₃NO₄
• Molecular Weight: 650.97
• EINECS: 229-999-3
• Product Categories: Amino Acids & Derivatives;Labeling and Diagnostics Reagents;Intermediates & Fine Chemicals;Pharmaceuticals;Isotope Labeled Compounds;Isotope Labelled Compounds
• Mol File: 5817-39-0.mol
• Article Data: 9

Chemical Properties

• Melting Point: 234-238 °C(lit.)
• Boiling Point: 534.6 °C at 760 mmHg
• Flash Point: 9℃
• Appearance: /powder
• Density: 2.387 g/cm³
• Storage Temp.: 2-8°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 2.17±0.20(Predicted)
• CAS DataBase Reference: REVERSE T3(CAS DataBase Reference)
• NIST Chemistry Reference: REVERSE T3(5817-39-0)
• EPA Substance Registry System: REVERSE T3(5817-39-0)

Safety Data

• Hazard Codes: Xn,T,F
• Statements: 36/37/38-20/21/22-39/23/24/25-23/24/25-11
• Safety Statements: 36-45-36/37-16
• RIDADR: UN1230 - class 3 - PG 2 - Methanol, solution
• WGK Germany: 3
• RTECS: AY6750000
• F: 8
• Hazardous Substances Data: 5817-39-0(Hazardous Substances Data)

Usage

Description

Either a derivative or precursor of thyroxine. Triiodothyronine increases themetabolic rate and oxygen consumption of animal tissues. Used in biochemical research, medicine (metabolic insufficiency).

Chemical Properties

Beige Powder

Uses

One of the hormones produced by the thyroid gland that is involved in the maintenance of metabolic homeostasis. Also produced in peripheral tissues as the active metabolite of Thyroxine.

Biological Activity

3,3',5'-triiodo-l-thyronine (reverse t3 or rt3) and 3,5,3'-triiodo-l-thyronine (t3) are the metabolism of thyroxine (t4) [1]. 3,3',5'-triiodo-l-thyronine is thyroid hormone receptors trα and trβ antagonist [1].thyroid hormones play important roles in the development of the mammalian brain by acting on migration and differentiation of neural cells, synaptogenesis, and myelination. the actions of thyroid hormones are mediated by nuclear thyroid hormone receptors (trs) and regulation of gene expression. trs have been also involved in adult brain function. in adult mice, trα1 deletion and a dominant negative mutant receptor expression induce consistent behavioral changes leading to severe anxiety and morphological changes in the hippocampus [2].the rt3 was about 1,000-fold less active at the thyroid hormone receptors trα and trβ compared with 3,3',5-triiodo-l-thyronine and commonly described as inactive [1].it has been reported that rt3 activates a native form of trα, trδα1, which lacks a nuclear localization signal and functions in the cytoplasm. through this action, rt3 initiates actin polymerization, particularly in astrocytes and neurons [3].

references

[1] nicod p, burger a, staeheli v, et al. a radioimmunoassay for 3, 3′, 5′-triiodo-l-thyronine in unextracted serum: method and clinical results[j]. the journal of clinical endocrinology & metabolism, 1976, 42(5): 823-829.[2] bernal j. thyroid hormone receptors in brain development and function[j]. nature clinical practice endocrinology & metabolism, 2007, 3(3): 249-259.[3] senese r, cioffi f, de lange p, et al. thyroid: biological actions of ‘nonclassical’thyroid hormones[j]. journal of endocrinology, 2014, 221(2): r1-r12.

Synthetic route

3',5'-Diiodothyronine (4192-14-7) → L-3,3',5'-triiodothyronine (5817-39-0)

Conditions	Yield
With iodine for 0.00833333h; Rate constant;

3-Monoiodothyronine (10468-90-3) → L-3,3',5'-triiodothyronine (5817-39-0)

Conditions	Yield
With ammonium hydroxide; iodine

L-thyroxine (51-48-9) → L-3,3',5'-triiodothyronine (5817-39-0)

Conditions	Yield
With diothiothreitol; rat liver microsomal protein 5'-T4-deiodinase (5'-T4Dase) In phosphate buffer at 37℃; for 0.5h; pH=7.4; Enzyme kinetics; Further Variations:; reaction time;
With Naphthalene-1,8-diselenol; D,L-dithiothreitol at 37℃; pH=7.5; Kinetics; pH-value; Concentration; Time; Reagent/catalyst; aq. phosphate buffer; regioselective reaction;
With C13H15NSe2; D,L-dithiothreitol at 37℃; pH=7.5; aq. phosphate buffer; regioselective reaction;

N-acetyl-3-iodo-L-tyrosine (1023-47-8) → L-3,3',5'-triiodothyronine (5817-39-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: (i) MeOH, TsOH, CH2Cl2, (ii) aq. NH3 2: (i) NaOEt, DMF, (ii) /BRN= 6464137/ 3: aq. HBr, AcOH 4: I2, aq. NH3 View Scheme

(S)-2-Acetylamino-3-[3-iodo-4-(4-methoxy-phenoxy)-phenyl]-propionamide (59302-20-4) → L-3,3',5'-triiodothyronine (5817-39-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: aq. HBr, AcOH 2: I2, aq. NH3 View Scheme

N-Acetyl-3-iodo-L-tyrosinamid (59302-19-1) → L-3,3',5'-triiodothyronine (5817-39-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: (i) NaOEt, DMF, (ii) /BRN= 6464137/ 2: aq. HBr, AcOH 3: I2, aq. NH3 View Scheme

C10H8SSe (903571-91-5) + L-thyroxine (51-48-9) → naphtho<1,8-cd>thiaselenole (64869-35-8) + L-3,3',5'-triiodothyronine (5817-39-0)

Conditions	Yield
With DL-dithiothreitol at 37℃; pH=7.5; aq. phosphate buffer; regioselective reaction;
at -20℃; regioselective reaction;

C13H15NSSe (1261500-99-5) + L-thyroxine (51-48-9) → C13H13NSSe (1261501-03-4) + L-3,3',5'-triiodothyronine (5817-39-0)

Conditions	Yield
With DL-dithiothreitol at 37℃; pH=7.5; aq. phosphate buffer;

L-thyroxine (51-48-9) + naphthalene-1,8-dithiol (25079-77-0) → L-3,3',5'-triiodothyronine (5817-39-0) + 1,8-naphthalenedisulfide (209-22-3)

Conditions	Yield
With DL-dithiothreitol at 37℃; pH=7.5; aq. phosphate buffer;

L-thyroxine (51-48-9) → 3'-Iodothyronine (4732-82-5) + 3-Monoiodothyronine (10468-90-3) + L-3,3'-Diiodothyronine (70-40-6, 58342-32-8, 4604-41-5) + 3',5'-Diiodothyronine (4192-14-7) + L-3,3',5'-triiodothyronine (5817-39-0) + O-(4-hydroxyphenyl)-3,5-diiodo-L-tyrosine (1596-67-4)

Conditions	Yield
With sodium tetrahydroborate; C10H8STe; D,L-dithiothreitol In aq. phosphate buffer at 37℃; for 0.5h; pH=7.5; Reagent/catalyst; regioselective reaction;

L-3,3',5'-triiodothyronine (5817-39-0) → 3,3'5'-triiodo-L-thyronine sulfate

Conditions	Yield
With chlorosulfonic acid; trifluoroacetic acid at 0℃;	21%

L-3,3',5'-triiodothyronine (5817-39-0) → 3'-Iodothyronine (4732-82-5) + 3-Monoiodothyronine (10468-90-3) + L-3,3'-Diiodothyronine (70-40-6, 58342-32-8, 4604-41-5) + 3',5'-Diiodothyronine (4192-14-7)

Conditions	Yield
With sodium tetrahydroborate; C10H8Te2; D,L-dithiothreitol In aq. phosphate buffer at 37℃; for 0.5h; pH=7.5; regioselective reaction;

L-3,3',5'-triiodothyronine (5817-39-0) → 3'-Iodothyronine (4732-82-5) + 3-Monoiodothyronine (10468-90-3) + L-3,3'-Diiodothyronine (70-40-6, 58342-32-8, 4604-41-5) + 3',5'-Diiodothyronine (4192-14-7) + O-(4-hydroxyphenyl)-3,5-diiodo-L-tyrosine (1596-67-4)

Conditions	Yield
With sodium tetrahydroborate; C10H8STe; D,L-dithiothreitol In aq. phosphate buffer at 37℃; for 0.5h; pH=7.5; Reagent/catalyst; regioselective reaction;

L-3,3',5'-triiodothyronine (5817-39-0) → 3'-Iodothyronine (4732-82-5) + 3-Monoiodothyronine (10468-90-3) + O-(4-hydroxyphenyl)-3,5-diiodo-L-tyrosine (1596-67-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: D,L-dithiothreitol; sodium tetrahydroborate; C10H8STe / aq. phosphate buffer / 0.5 h / 37 °C / pH 7.5 2: D,L-dithiothreitol; sodium tetrahydroborate; C10H8STe / aq. phosphate buffer / 0.5 h / 37 °C / pH 7.5 View Scheme

di-tert-butyl dicarbonate (24424-99-5) + L-3,3',5'-triiodothyronine (5817-39-0) → Boc-rT3-OH

Conditions	Yield
With triethylamine In 1,4-dioxane; water at 0 - 20℃; for 30.5h;

Upstream product

• 51-48-9 L-thyroxine 
• 25079-77-0 naphthalene-1,8-dithiol 
• 1261500-99-5 C₁₃H₁₅NSSe 
• 903571-91-5 C₁₀H₈SSe 
• 59302-19-1 N-Acetyl-3-iodo-L-tyrosinamid 
• 59302-20-4 (S)-2-Acetylamino-3-[3-iodo-4-(4-methoxy-phenoxy)-phenyl]-propionamide 
• 1023-47-8 N-acetyl-3-iodo-L-tyrosine 
• 10468-90-3 3-Monoiodothyronine 
• 4192-14-7 3',5'-Diiodothyronine 

Downstream Products

• 4732-82-5 3'-Iodothyronine 
• 10468-90-3 3-Monoiodothyronine 
• 70-40-6 L-3,3'-Diiodothyronine 
• 4192-14-7 3',5'-Diiodothyronine 
• 1596-67-4 O-(4-hydroxyphenyl)-3,5-diiodo-L-tyrosine 

Relevant articles and documents

Biomimetic deiodination of thyroid hormones and iodothyronamines-a structure-activity relationship study

Mammalian selenoenzymes, iodothyronine deiodinases (DIOs), catalyze the tyrosyl and phenolic ring deiodination of thyroid hormones (THs) and play an important role in maintaining the TH concentration throughout the body. These enzymes also accept the decarboxylated thyroid hormone metabolites, iodothyronamines (TAMs), as substrates for deiodination. Naphthalene-based selenium and/or sulphur-containing small molecules have been shown to mediate the regioselective tyrosyl ring deiodination of thyroid hormones and their metabolites. Herein, we report on the structure-activity relationship studies of a series of peri-substituted selenium-containing naphthalene derivatives for the deiodination of thyroid hormones and iodothyronamines. Single crystal X-ray crystallographic and 77Se NMR spectroscopic studies indicated that the intramolecular Se?X (X = N, O and S) interactions play an important role in the deiodinase activity of the synthetic mimics. Furthermore, the decarboxylated metabolites, TAMs, have been observed to undergo slower tyrosyl ring deiodination than THs by naphthyl-based selenium and/or sulphur-containing synthetic deiodinase mimics and this has been explained on the basis of the strength of Se?I halogen bonding formed by THs and TAMs.

Regioselective deiodination of iodothyronamines, endogenous thyroid hormone derivatives, by deiodinase mimics

Iodothyronine deiodinases (IDs) are mammalian selenoenzymes that play an important role in the activation and inactivation￡ of thyroid hormones. It is known that iodothyronamines (TnAMs), produced by the decarboxylation of thyroid hormones, act as substrates for deiodinases. To understand whether decarboxylation alters the rate and/or regioselectivity of deiodination by using synthetic deiodinase mimics, we studied the deiodination of different iodothyronamines. The triiodo derivative 3,3,5-triiodothyronamine (T3 AM) is deiodinated at the inner ring by naphthyl-based deiodinase mimics, which is similar to the deiodination of 3,3,5-triiodothyronine (T3). However, T3 AM undergoes much slower deiodination than T3. Detailed experimental and theoretical investigations suggest that T3 AM forms a weaker halogen bond with selenium donors than T3. Kinetic studies and single-crystal X-ray structures of T3 and T3 AM reveal that intermolecular I...I interactions may play an important role in deiodination. The formation of hydrogen- and halogen-bonding assemblies, which leads to the formation of a dimeric species of T3 in solution, facilitates the interactions between the selenium and iodine atoms. In contrast, T3 AM, which does not have I...I interactions, undergoes much slower deiodination.

Deiodination of thyroid hormones by iodothyronine deiodinase mimics: Does an increase in the reactivity alter the regioselectivity?

Organoselenium compounds as functional mimics of iodothyronine deiodinase are described. The naphthyl-based compounds having two selenol groups are remarkably efficient in the inner-ring deiodination of thyroxine. The introduction of a basic amino group in close proximity to one of the selenol moieties enhances the deiodination. This study suggests that an increase in the nucleophilic reactivity of the conserved Cys residue at the active site of deiodinases is very important for effective deiodination.