Zalcitabine

Base Information

• Chemical Name: Zalcitabine
• CAS No.: 7481-89-2
• Molecular Formula: C9H13N3O3
• Molecular Weight: 211.221
• Hs Code.: 2934990002
• European Community (EC) Number: 620-762-3
• NSC Number: 759655
• UNII: 6L3XT8CB3I
• DSSTox Substance ID: DTXSID0023747
• Nikkaji Number: J277.119E
• Wikipedia: Zalcitabine
• Wikidata: Q2344582
• NCI Thesaurus Code: C430
• Pharos Ligand ID: 7UXNRXQLDRZ5
• Metabolomics Workbench ID: 43203
• ChEMBL ID: CHEMBL853
• Mol file: 7481-89-2.mol

Synonyms:2',3' Dideoxycytidine;2',3'-Dideoxycytidine;ddC (Antiviral);Dideoxycytidine;Hivid;HIVID Roche;NSC 606170;NSC-606170;NSC606170;Zalcitabine

Chemical Property of Zalcitabine

Chemical Property:

• Appearance/Colour: white to off-white cyrstalline powder
• Melting Point: 217-218 °C(lit.)
• Refractive Index: 78 ° (C=0.5, H2O)
• Boiling Point: 415 °C at 760 mmHg
• PKA: 14.44±0.10(Predicted)
• Flash Point: 204.8 °C
• PSA: 90.37000
• Density: 1.57 g/cm³
• LogP: 0.07660
• Storage Temp.: 2-8°C
• Solubility.: DMSO (Slightly, Heated), Methanol (Slightly), Water (Slightly, Sonicated)
• Water Solubility.: 5-10 g/100 mL at 19 ºC
• XLogP3: -1.3
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 2
• Exact Mass: 211.09569129
• Heavy Atom Count: 15
• Complexity: 327

Purity/Quality:

98%min ^*data from raw suppliers

Zalcitabine ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn,C
• Hazard Codes: Xn,C
• Statements: 40-36/37-34
• Safety Statements: 22-36-45-36/37/39-27-26

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1CC(OC1CO)N2C=CC(=NC2=O)N
• Isomeric SMILES: C1C[C@@H](O[C@@H]1CO)N2C=CC(=NC2=O)N
• Recent ClinicalTrials: A Phase I Concentration-Targeted Multidose Study of Atevirdine Mesylate ( U-87201E ), AZT, and ddI or ddC
• Recent EU Clinical Trials: THERAPEUTIC SIMPLIFICATION WITH THYMIDINE ANALOGUR SPARING REGIMENS IN PATIENTS ON EFFECTIVE HAART: A CONTROLLED, RANDOMIZED STUDY
• Description: Zalcitabine is an orally active dideoxynucleoside andog for combination use with zidovudine in advanced HIV infection and also as monotherapy for AIDS patients who cannot tolerate or have not responded to zidovudine. It has a similar mechanism of action (inhibition of reverse transcriptase) to didanosine. Like didanosine, its side effect profile includes peripheral neuropathy. Unlike zidovudine, zalcitabine does not cause bone marrow suppression. Zalcitabine is an analog of pyrimidine derived from deoxycytidine with the replacement of the hydroxyl group in position 3’ with a hydrogen. In cells, it is phosphorylated to the active triphosphate form, ddCTP, which acts as a substrate for HIV reverse transcriptase (Ki = 51 nM). It incorporates into viral DNA where it terminates chain elongation when the missing hydroxyl group is encountered. Zalcitabine was the third antiretroviral approved by the FDA for treatment of HIV infection and AIDS.
• Uses: ammonia detoxicant, diagnostic aid A pyrimidine nucleoside analogue with antiviral activity A pyrimidine nucleoside analogue with antiviral activity.
• Indications: Zalcitabine (ddC, Hivid) is a cytidine analogue active against HIV-1, HIV-2, and hepatitis B virus. It is used for the treatment of HIV infection in adults and asymptomatic children as part of a multidrug regimen. It may be less effective than the other nucleoside inhibitors and is used less frequently.
• Therapeutic Function: Antiviral, Immunosuppressive

Technology Process of Zalcitabine

There total 3 articles about Zalcitabine 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:

3'-Deoxythymidine (3416-05-5) + CYTIDINE (65-46-3) → 2`,3`-dideoxycytidine (7481-89-2) + 5-Methyluridine (1463-10-1,642082-80-2)

Guidance literature:

native N-deoxyribosyl transferase of Lactobacillus leichmannii LL; at 37 ℃; pH=6.44; Conversion of starting material; Enzymatic reaction; Aqueous citrate buffer;

Reference yield:

2',3'-Dideoxyuridine (5983-09-5) → 2`,3`-dideoxycytidine (7481-89-2)

Guidance literature:

Multi-step reaction with 3 steps

1: pyridine / 4 °C

2: 4-chlorophenyl phosphorodichloridate, pyridine / 72 h / Ambient temperature

3: 1.) NH₄OH, 2.) NH₃ / 1.) dioxane, RT, 5 h, 2.) MeOH, RT, pressure, overnight

With pyridine; ammonium hydroxide; 4-chlorophenylphosphorodichloridate;

DOI:10.1021/jm00385a033

Reference yield:

(5S)-5-(hydroxymethyl)-2-oxo-tetrahydrofuran (32780-06-6) → 2`,3`-dideoxycytidine (7481-89-2)

Guidance literature:

Multi-step reaction with 6 steps

1: 90 percent / imidazole / CH₂Cl₂ / 3 h

2: DIBAL-H / CH₂Cl₂; toluene / 2 h / -90 °C

3: molecular sieves (4 Angstroem), BF₃*OEt₂ / diethyl ether / 0.5 h

4: 1.) 1,1,1,3,3,3,-hexamethyldisilazane, ammonium sulfate, 2.) SnCl₄, TMSOTf / 1.) reflux, 2 h, 2.) 1,2-dichloroethane, RT, 2 h

5: TBAF / tetrahydrofuran / 8 h

6: K₂CO₃ / methanol

With 1H-imidazole; ammonium sulfate; trimethylsilyl trifluoromethanesulfonate; 4 A molecular sieve; boron trifluoride diethyl etherate; tetrabutyl ammonium fluoride; tin(IV) chloride; diisobutylaluminium hydride; potassium carbonate; 1,1,1,3,3,3-hexamethyl-disilazane; In tetrahydrofuran; methanol; diethyl ether; dichloromethane; toluene;

DOI:10.1021/jm960400q

upstream raw materials:

3'-Deoxythymidine

CYTIDINE

(5S)-5-(hydroxymethyl)-2-oxo-tetrahydrofuran

2',3'-Dideoxyuridine

Downstream raw materials:

N⁴-<(diisopropylamino)methylene>-2',3'-dideoxycytidine

Oxalic acid (2S,5R)-5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethyl ester 4-nitro-phenyl ester

5-iodo-2',3'-dideoxycytidine

2',3'-dideoxy-5-bromocytidine

Refernces

• 1、 -. "Lactobacillus Fermentum N-Desoxyribosyl Transferases and the Use Thereof for Enzymatic Synthesis of 2', 3' - Didesoxynucleosides and 2',3'- Didehydro-2',3'- Didesoxynucleosides". Page/Page column 6-8. . Retrieved 2008/06/13.
• 2、 Beach, J. Warren,Kim, Hea O.,Jeong, Lak S.,Nampalli, Satyanarayana,Islam, Qamrul,et al.. "A Highly Stereoselective Synthesis of Anti-HIV 2',3'-Dideoxy- and 2',3'-Didehydro-2',3'-dideoxynucleosides". . p. 3887 - 3894. Retrieved 2007/10/02.