Methyldopa

Base Information

• Chemical Name: Methyldopa
• CAS No.: 555-30-6
• Deprecated CAS: 133161-54-3,1339-75-9,4290-08-8,88620-56-8,779-08-8,1339-75-9,4290-08-8,779-08-8
• Molecular Formula: C10H13NO4
• Molecular Weight: 211.218
• Hs Code.: 29181990
• European Community (EC) Number: 209-089-2
• NSC Number: 760080
• UNII: M4R0H12F6M
• DSSTox Substance ID: DTXSID5023295
• Nikkaji Number: J9.247I
• Wikipedia: Methyldopa
• Wikidata: Q412621
• NCI Thesaurus Code: C175729
• RXCUI: 1545996
• Pharos Ligand ID: KDTN5WVPYYLW
• Metabolomics Workbench ID: 41522
• ChEMBL ID: CHEMBL459
• Mol file: 555-30-6.mol

Synonyms:Aldomet;alpha Methyl L Dopa;alpha Methyldopa;alpha-Methyl-L-Dopa;alpha-Methyldopa;Alphamethyldopa;Apo Methyldopa;Apo-Methyldopa;Dopamet;Dopegit;Dopegyt;Dopergit;Hydopa;Meldopa;Methyldopa;Methyldopate;Nu Medopa;Nu-Medopa;Sembrina

Chemical Property of Methyldopa

Chemical Property:

• Appearance/Colour: Colorless or almost colorless crystals or white to yellowish-white fine powder
• Vapor Pressure: 2.19E-08mmHg at 25°C
• Melting Point: 300 °C
• Refractive Index: -14 ° (C=1, H2O)
• Boiling Point: 441.6 °C at 760 mmHg
• PKA: 2.28±0.26(Predicted)
• Flash Point: 220.9 °C
• PSA: 103.78000
• Density: 1.403 g/cm³
• LogP: 1.14260
• Storage Temp.: Store at RT
• Water Solubility.: 10g/L(temperature not stated)
• XLogP3: -1.9
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 3
• Exact Mass: 211.08445790
• Heavy Atom Count: 15
• Complexity: 246

Purity/Quality:

99.9% ^*data from raw suppliers

L-α- ^*data from reagent suppliers

Safty Information:

• Safety Statements: S24/25:Avoid contact with skin and eyes.

MSDS Files:

SDS file from LookChem

Useful:

• Chemical Classes: Other Uses -> Pharmaceuticals
• Drug Classes: Antihypertensive Agents
• Canonical SMILES: CC(CC1=CC(=C(C=C1)O)O)(C(=O)O)N
• Isomeric SMILES: C[C@](CC1=CC(=C(C=C1)O)O)(C(=O)O)N
• Recent ClinicalTrials: Effect of Methyldopa on MHC Class II Antigen Presentation in Type 1 Diabetes
• Description: Methyldopa is an α-methoxylated derivative of levodopa that exhibits hypotensive action by reducing overall peripheral vascular resistance and reducing heart work. Antihypertensive action of methyldopa consists of the biotransformation of methyldopa into methylnoradrenaline (methylnorepinephrine), which acts as a “pseudo neurotransmitter.” The current, universally accepted point of view is that the action of methyldopa is carried out through the CNS, where methylnorepinephrine, a powerful stimulant of α-adrenergic receptors of the medulla, inhibits the vasomotor center.
• Uses: It is prescribed for arterial hypertension and hypertensive crises. L-(-)-a-Methyldopa is an anti-Parkinson’s drug that has been used in anti-Parkinson’s mixtures. Antihypertensor;L-aromatic aminoacid decarboxylase inhibitor vitamin, coenzyme B12
• Therapeutic Function: Antihypertensive
• Biological Functions: The spectrum of activity of α-methyldopa (Aldomet) lies between those of the more potent agents, such as guanethidine, and the milder antihypertensives, such as reserpine. α-Methyldopa is a structural analogue of dihydroxyphenylalanine (dopa) and differs from dopa only by the presence of a methyl group on the -carbon of the side chain.
• Clinical Use: α-Methyldopa is not generally believed to be suitable for monotherapy of primary hypertension. Because plasma volume increases as the duration of α-methyldopa therapy is extended, the drug should be used in conjunction with a diuretic; this will produce a significantly greater fall in blood pressure than would occur with either drug used alone. Because α-methyldopa lowers blood pressure without compromising either renal blood flow or the glomerular filtration rate, it is particularly valuable in hypertension complicated by renal disease. However, if end-stage renal failure accompanies severe hypertension,α-methyldopa may not be effective. The presence of α-methyldopa and its metabolites in the urine reduces the diagnostic value of urinary catecholamine measurements as an indicator of pheochromocytoma, since these substances interfere with the fluorescence assay for catecholamines.
• Drug interactions: Potentially hazardous interactions with other drugs Anaesthetics: enhanced hypotensive effect. Antidepressants: avoid concomitant use with MAOIs. Lithium: neurotoxicity (without increased plasma lithium concentrations). Salbutamol: acute hypotension reported with salbutamol infusions.

Technology Process of Methyldopa

There total 19 articles about Methyldopa which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 86.0%

(S)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid hydrochloride (1369423-51-7,884-39-9) → methyldopa (555-30-6,555-29-3,88620-56-8)

Guidance literature:

With methyloxirane; In ethanol; for 3h; Inert atmosphere; Reflux;

DOI:10.1021/jo301588t

Reference yield:

C15H21NO5 → methyldopa (555-30-6,555-29-3,88620-56-8)

Guidance literature:

With hydrogen bromide; In water; at 60 ℃; for 4h; Large scale;

Reference yield:

4-bromomethyl-1,2-dimethoxybenzene (21852-32-4) → methyldopa (555-30-6,555-29-3,88620-56-8)

Guidance literature:

Multi-step reaction with 2 steps

1: tetrahydrofuran; hexane / 2 h / -78 - 0 °C

2: aq. 6N HCl / 4 h / 175 - 185 °C

With hydrogenchloride; In tetrahydrofuran; hexane;

DOI:10.1002/hlca.19850680118

upstream raw materials:

(S)-N-Acetyl-α-methyl-β-(3,4-dimethoxyphenyl)alanin

(S)-3-(3,4-dimethoxyphenyl)-2-methylalanine

(S)-2-amino-3-(3,4-dimethoxyphenyl)-2-methylpropionamide

N-Chloroacetyl-α-methyl-DOPA

Downstream raw materials:

αMeDopa-OMe*HCl

methyl-2 <(tri-O-benzoyl-2',3',5' β-D-ribofuranosyl)-3 hydroxy-4 phenyl>-3 alanine

N-acetyl tri-O-benzoyl-2,3,5-D-ribofuranosylamine

1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose

Refernces

• 1、 Mai, Thi Thoa,Viswambharan, Baby,Gori, Didier,Kouklovsky, Cyrille,Alezra, Valerie. "Memory of chirality of tertiary aromatic amide: Application to the asymmetric synthesis of (S)-α-methylDOPA". . p. 8797 - 8801,5. Retrieved 2020/09/15.
• 2、 Chenault, H. Keith,Dahmer, Juergen,Whitesides, George M.. "Kinetic Resolution of Unnatural and Rarely Occuring Amino Acids: Enantioselective Hydrolysis of N-Acyl Amino Acids Catalyzed by Acylase I". . p. 6354 - 6364. Retrieved 2007/10/02.