Cycloserine

Base Information

• Chemical Name: Cycloserine
• CAS No.: 68-41-7
• Molecular Formula: C3H6N2O2
• Molecular Weight: 102.093
• Hs Code.: 29419090
• European Community (EC) Number: 200-688-4
• NSC Number: 756712
• UNII: 95IK5KI84Z
• DSSTox Substance ID: DTXSID8022870
• Nikkaji Number: J8.592H
• Wikipedia: Cycloserine
• Wikidata: Q418508
• NCI Thesaurus Code: C47466
• RXCUI: 3007
• Metabolomics Workbench ID: 27997
• ChEMBL ID: CHEMBL771
• Mol file: 68-41-7.mol

Synonyms:Cycloserine;R-4-Amino-3-isoxazolidinone;Seromycin

Chemical Property of Cycloserine

Chemical Property:

• Appearance/Colour: White to pale yellow cryst. powder
• Melting Point: 147ºC
• Refractive Index: 1.5110 (estimate)
• Boiling Point: 267ºC
• PKA: pKa 4.5 (Uncertain)
• PSA: 64.35000
• Density: 1.278 g/cm³
• LogP: -0.59580
• Storage Temp.: −20°C
• Sensitive.: Air Sensitive
• Solubility.: water: soluble50mg/mL, clear, colorless to light yellow
• Water Solubility.: SOLUBLE
• XLogP3: -1.5
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 0
• Exact Mass: 102.042927438
• Heavy Atom Count: 7
• Complexity: 92.9

Purity/Quality:

99% ^*data from raw suppliers

D-Cycloserine ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 5-20
• Safety Statements: 38-36/37-24/25

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Antituberculosis Agents
• Canonical SMILES: C1C(C(=O)NO1)N
• Isomeric SMILES: C1[C@H](C(=O)NO1)N
• Recent ClinicalTrials: Treating Urological Chronic Pelvic Pain Syndrome (UCPPS) Pain
• Recent EU Clinical Trials: Manipulating NMDA-dependent learning to alter nocebo effects: A pharmacological fMRI study on pain and itch.
• Uses: Used as an antibiotic medicine in the treatment of drug-resistant Mycobacterium tuberculosis infection. Biochemical research D-cycloserine has been used to inhibit serine hydroxymethyltransferase. D-Cycloserine inhibits cell wall biosynthesis (D-Ala peptide bond formation). D-Cycloserine also prevents conversion of D-Ala to L-Ala. D-Cycloserine is an bacteriostatic. D-Cycloserine is an antibiot ic against Gram-negative bacteria.
• Description: D-Cycloserine (68-41-7) is a partial agonist at the glycine modulatory site of NMDA glutamatergic receptors.1?Blocks kainate-induced seizures2?and displays anticonvulsant effects3?in rat models. D-Cycloserine facilitates synaptic plasticity but impairs glutamatergic neurotransmission in rat hippocampal slices.4?Second-line drug for the treatment of tuberculosis. ?Enhances activity-dependent plasticity in human adults.5
• Indications: Cycloserine is a broad-spectrum antibiotic produced by Streptomyces orchidaceus. It is structural analogue of Dalanine and acts through a competitive inhibition of the D-alanine that is involved in bacterial cell wall synthesis. Cycloserine is inhibitory to M. tuberculosis and active against Escherichia coli, S. aureus, and Enterococcus, Nocardia, and Chlamydia spp. It is used in the treatment of MDR tuberculosis and is useful in renal tuberculosis, since most of the drug is excreted unchanged in the urine.
• Therapeutic Function: Antitubercular
• Clinical Use: Neurological symptoms, which tend to appear in the first week of therapy, consist of dizziness, confusion, irritability, psychotic behavioral changes, and even suicidal ideation. Cycloserine is contraindicated in patients with underlying psychiatric and seizure disorders.Other side effects include occasional peripheral neuropathy and low magnesium levels. D-(+)-4-Amino-3-isoxazolidinone (Seromycin) is an antibioticthat has been isolated from the fermentation beer of threedifferent Streptomyces species: S. orchidaceus, S. garyphalus,and S. lavendulus. It occurs as a white to pale yellow crystallinematerial that is very soluble in water. It is stable in alkaline,but unstable in acidic, solutions. The compoundslowly dimerizes to 2,5-bis(aminoxymethyl)-3,6-diketopiperazinein solution or standing.The structure of cycloserine was reported simultaneouslyby Kuehl et al. and Hidy et al.81 to be D-( +)-4-amino-3-isoxazolidinone. It has been synthesized byStammer et al. and by Smart et al.83 Cycloserine is stereochemicallyrelated to D-serine. However, the L-form hassimilar antibiotic activity.Although cycloserine exhibits antibiotic activity invitro against a wide spectrum of both Gram-negative andGram-positive organisms, its relatively weak potency andfrequent toxic reactions limit its use to the treatment of tuberculosis.It is recommended for patients who fail to respondto other tuberculostatic drugs or who are known tobe infected with organisms resistant to other agents. It isusually administered orally in combination with otherdrugs, commonly isoniazid.
• Drug interactions: Potentially hazardous interactions with other drugs Alcohol: Increased risk of seizures.

Technology Process of Cycloserine

There total 39 articles about Cycloserine 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: 94.25%

Methyl (2R)-2-amino-3-chloropropionate hydrochloride (17136-54-8) → cycloserine (68-41-7)

Guidance literature:

With hydrogenchloride; acetone oxime; In methanol; at 65 ℃; for 1h; Temperature;

Reference yield: 80.0%

methyl (2R)-2-amino-3-(aminooxy)propanoate (29491-80-3) → cycloserine (68-41-7)

Guidance literature:

methyl (2R)-2-amino-3-(aminooxy)propanoate; With sodium hydroxide; In water; at -5 - 0 ℃; for 3h;

With acetic acid; In water; isopropyl alcohol; at -12 - -8 ℃; for 1h; pH=6.7 - 6.9;

DOI:10.1007/s10593-018-2197-y

Reference yield: 65.0%

D-cycloserine-L-tartrate (72270-01-0) → cycloserine (68-41-7)

Guidance literature:

With Amberlite IR-120 PLUS ion exchange resin (sodium form); In water; Inert atmosphere;

DOI:10.3987/COM-12-12553

upstream raw materials:

3-chloro-D-alanine hydroxyamide

N-benzyloxycarbonyl-O-(toluene-4-sulfonyl)-D-serine benzyloxyamide

(R)-4-benzyloxycarbonylamino-3-oxo-isoxazolidine-2-carboxylic acid benzyl ester

tert-butyl N-[(4R)-3-oxoisoxazolidin-4-yl]carbamate

Downstream raw materials:

4-(4-bromo-benzylideneamino)-isoxazolidin-3-one

α-N-acetyl-D-cycloserine

D-4-(4'-fluorobenzamido)-3-isoxazolidone

N-((R)-3-Oxo-isoxazolidin-4-yl)-3-trifluoromethyl-benzamide

Refernces

• 1、 Matoba, Yasuyuki,Uda, Narutoshi,Kudo, Mako,Sugiyama, Masanori. "Cyclization mechanism catalyzed by an ATP-grasp enzyme essential for d-cycloserine biosynthesis". . p. 2763 - 2778. Retrieved 2020/01/24.
• 2、 -. "Method for preparing D-cycloserine through one-pot method". Paragraph 0026-0033. . Retrieved 2019/10/01.