| Identification | Back Directory | [Name]
Thiamphenicol | [CAS]
15318-45-3 | [Synonyms]
8065c.b.
Neomyson
NSC 522822
win-5063-2
thiocymetin
thiophenicol
THIAMPHENICOL
D-Thiocymetin
D-Thiophenicol
THIAMPHENICHOL
ThiaMphenicol API
dextrosulphenidol
methylsulfonyl chloramphenicol
ThiaMphenicol / Methylsulfonyl chloraMphenicol
ThiocyMetin, Thiophenicol, Win 5062-2, NSC 522822
ThiamphenicolBP,
98.0-100.5% (Assay)
D-d-threo-2-Dichloroacetamido-1-(4-methylsulfonylphenyl)-1,3-propanediol
acetamide,2,2-dichloro-n-(beta-hydroxy-alpha-(hydroxymethyl)-p-(methylsulfonyl
D-threo-(1R,2R)-1-(p-Methylsulfonylphenyl)-2-dichloroacetamido-1,3-propanediol
2,2-Dichloro-N-[(1R,2R)-1,3-dihydroxy-1-(4-methylsulfonylphenyl)propan-2-yl]acetamide
2,2-Dichloro-N-[(1R,2R)-1,3-dihydroxy-1-[4-(methylsulfonyl)phenyl]-2-propyl]acetamide
2,2-dichloro-N-[(1R,2R)-1,3-dihydroxy-1-(4-Methanesulfonylphenyl)propan-2-yl]acetaMide
2,2-Dichloro-N[(1R,2R)-2-hydroxy-1-hydroxymethyl-2-(4-methylsulphonylphenyl)-acetamide
D-threo-2,2-Dichloro-N-(b-hydroxy-a-[hydroxymethyl]-4-[methylsulfonyl]phenethyl)acetamide
d-threo-2,2-dichloro-n-(β-hydroxy-α-[hydroxymethyl]-4-[methylsulfonyl]phenethyl)acetamide
2,2-Dichloro-N-[(1R,2R)-2-hydroxy-1-hydroxymethyl-2-(4-methylsulfonylphenyl)ethyl]acetamide
(+)-2,2-Dichloro-N-[(αR,βR)-β-hydroxy-α-(hydroxymethyl)-4-(methylsulfonyl)phenethyl]acetamide
Acetamide, 2,2-dichloro-N-(1R,2R)-2-hydroxy-1-(hydroxymethyl)-2-4-(methylsulfonyl)phenylethyl-
D-THREO-2,2-DICHLORO-N-(BETA-HYDROXY-ALPHA-[HYDROXYMETHYL]-4-[METHYLSULFONYL]PHENETHYL)ACETAMIDE
D-THREO-2,2-DICHLORO-N-[BETA-HYDROXY-ALPHA-(HYDROXYMETHYL)-P-(METHYL-SULFONYL)PHENETHYL]ACETAMIDE
Thiamphenicol,D-threo-2,2-Dichloro-N-(β-hydroxy-α-[hydroxymethyl]-4-[methylsulfonyl]phenethyl)acetamide
Acetamide, 2,2-dichloro-N-[(1R,2R)-2-hydroxy-1-(hydroxymethyl)-2-[4-(methylsulfonyl)phenyl]ethyl]- (9CI)
Acetamide, 2,2-dichloro-N-[2-hydroxy-1-(hydroxymethyl)-2-[4-(methylsulfonyl)phenyl]ethyl]-, [R-(R*,R*)]-
Acetamide, 2,2-dichloro-N-[b-hydroxy-a-(hydroxymethyl)-p-(methylsulfonyl)phenethyl]-, D-threo-(+)- (8CI) | [EINECS(EC#)]
239-355-3 | [Molecular Formula]
C12H15Cl2NO5S | [MDL Number]
MFCD00467983 | [MOL File]
15318-45-3.mol | [Molecular Weight]
356.22 |
| Chemical Properties | Back Directory | [Appearance]
Off-White Solid | [Melting point ]
163-166 °C
| [alpha ]
D25 +12.9° (ethanol) | [density ]
1.3281 (rough estimate) | [refractive index ]
1.6000 (estimate) | [storage temp. ]
-20°C Freezer, Under Inert Atmosphere | [solubility ]
ethanol: 50 mg/mL, clear, colorless
| [Boiling point ]
695.9±55.0 °C(Predicted) | [form ]
powder | [pka]
11.05±0.46(Predicted) | [color ]
white to off-white | [Water Solubility ]
Soluble in acetonitrile or DMF. Slightly soluble in water | [Merck ]
13,9372 | [BRN ]
2819542 | [Major Application]
clinical | [InChI]
1S/C12H15Cl2NO5S/c1-21(19,20)8-4-2-7(3-5-8)10(17)9(6-16)15-12(18)11(13)14/h2-5,9-11,16-17H,6H2,1H3,(H,15,18)/t9-,10-/m1/s1 | [InChIKey]
OTVAEFIXJLOWRX-NXEZZACHSA-N | [SMILES]
CS(=O)(=O)c1ccc(cc1)[C@@H](O)[C@@H](CO)NC(=O)C(Cl)Cl | [CAS DataBase Reference]
15318-45-3 | [EPA Substance Registry System]
Acetamide, 2,2-dichloro-N-[(1R,2R)-2- hydroxy-1-(hydroxymethyl)- 2-[4-(methylsulfonyl)phenyl] ethyl]-(15318-45-3) |
| Safety Data | Back Directory | [Safety Statements ]
22-24/25 | [WGK Germany ]
2
| [RTECS ]
AB6680000
| [REACH Registrations]
Active | [HS Code ]
29414000 | [Storage Class]
11 - Combustible Solids | [Toxicity]
human,TDLo,unreported,214mg/kg/10D (214mg/kg),BEHAVIORAL: SLEEPGASTROINTESTINAL: NAUSEA OR VOMITINGSKIN AND APPENDAGES (SKIN): "DERMATITIS, OTHER: AFTER SYSTEMIC EXPOSURE",Arzneimittel-Forschung. Drug Research. Vol. 24, Pg. 944, 1974. |
| Hazard Information | Back Directory | [Originator]
Thiophenicol,Clin Midy,France,1967 | [Definition]
ChEBI:Thiamphenicol is a sulfone and a monocarboxylic acid amide. It has a role as an immunosuppressive agent and an antimicrobial agent. | [Manufacturing Process]
A mixture of 50 parts by weight of racemic 2-acetylamino-1-(4-
methylmercaptophenyl)-1,3-propanediol, 100 parts by weight of concentrated
hydrochloric acid, and 500 parts by weight of water was warmed on a steam
bath for thirty minutes. The resulting solution was cooled to about 40°C and
was then made strongly alkaline by addition of 35% aqueous sodium
hydroxide solution. The alkaline solution was then refrigerated. The white solid
which separated from the cooled solution was collected on a filter. There was
thus obtained 27 parts by weight of 2-amino-1-(4-methylmercaptophenyl)-
1,3-propanediol. This product melted at 130.7°C to 131.9°C after
recrystallization from methanol.
This compound was converted to the tartrate and the optical isomers were
resolved.
A mixture of 1.1 g of 2-amino-1-(4-methylmercaptophenyl)-1,3-propanediol,
obtained as described above and 1.6 ml of ethyl dichloroacetate was heated
on a steam bath for three hours. The resulting viscous yellow oil was
dissolved in 25 ml of ethylene chloride and filtered hot with charcoal, and the
filtrate was allowed to cool to about 25°C. From the filtrate there separated
0.92 g of tiny white leaflets which were collected on a filter. Recrystallization
of this product, which was a dextro-rotary form of 2-dichloroacetylamino-1-(4-
methylmercaptophenyl)-1,3-propanediol from nitroethane yielded the pure
product, which melted at 111.6°C to 112.6°C.
7 g of the 2-dichloroacetylamino-1-(4-methylmercaptophenyl)-1,3-propanediol
obtained as described above was dissolved in 30 ml of acetone. To this
solution there was added dropwise with stirring 10 ml of 40% peracetic acid.
The temperature during the reaction was maintained at 39°C to 45°C by
cooling the reaction vessel. After stirring the mixture for two hours, it was
diluted with 100 ml of water and the solution allowed to stand over the
weekend in the refrigerator. The solid which separated from solution was
collected on a filter, washed several times with ice water, and dried overnight
at 70°C. | [Therapeutic Function]
Antibacterial | [Antimicrobial activity]
It is generally less active than chloramphenicol,
but is equally active against Str. pyogenes, Str. pneumoniae,
H. influenzae and N. meningitidis, including some strains resistant to chloramphenicol. It is more actively bactericidal
against Haemophilus and Neisseria spp.
| [Acquired resistance]
There is complete cross-resistance with chloramphenicol in
those bacteria which elaborate acetyltransferase, although the
affinity of the enzyme for thiamphenicol is lower. Organisms
that owe their resistance to other mechanisms may be
susceptible. | [Pharmacokinetics]
An oral dose of 500 mg produces a peak plasma level of
3–6 mg/L after about 2 h. The plasma half-life is 2.6–3.5
h. It is said to reach the bronchial lumen in concentrations
sufficient to exert a bactericidal effect on H. influenzae.
Unlike chloramphenicol it is not a substrate for
hepatic glucuronyl transferase; it is not eliminated by conjugation,
and its half-life is not affected by phenobarbital
induction.
About 50% of the dose can be recovered in an active form
in the urine within 8 h and 70% over 24 h. The drug is correspondingly
retained in the presence of renal failure, and
in anuric patients the plasma half-life has been reported to
be 9 h, a value not significantly affected by peritoneal dialysis.
Biliary excretion is believed to account for removal of
the antibiotic in anuric patients. The plasma concentration
is elevated and half-life prolonged in patients with hepatitis
or cirrhosis. | [Clinical Use]
Similar to that of chloramphenicol. | [Side effects]
There are no reports of irreversible bone-marrow toxicity.
This has been related to the absence of the nitro group, and
hence its reduction products, and differences in the biochemical
effects of thiamphenicol and chloramphenicol on mammalian
cells. It exerts a greater dose-dependent reversible
depression of hemopoiesis and immunogenesis than chloramphenicol,
and has been used for its immunosuppressive effect.
Therapeutic doses (1–1.5 g) are likely to depress erythropoiesis
in the elderly or others with impaired renal function. | [Synthesis]
Thiamphenicol, threo-(1R,2R)-2-(dichloroacetamido)-1-[(4-methylsulfonyl)phenyl]-1,3-propanediol, is a fully synthetic analogue of chloramphenicol. Several stereoselective routes have been reported, all of which share the construction of the key intermediate (1R,2R)-2-amino-1-[4-(methylthio)phenyl]-1,3-propanediol ((-)-3), followed by dichloroacetylation and sulfide-to-sulfone oxidation.
From commercially available 4-(methylthio)benzaldehyde 8, vinylmagnesium bromide addition gave allylic alcohol 9, oxone oxidation gave sulfone 10 (87% yield), and Sharpless asymmetric epoxidation under kinetic resolution with (-)-DIPT gave chiral epoxy alcohol 11 (42% chemical yield, 95.1% ee). This was converted to (+)-thiamphenicol via dichloroacetonitrile/NaH to the epoxy trichloroimidate 12 followed by BF3·OEt2-mediated intramolecular epoxide opening with in situ oxazoline hydrolysis (four steps total) [1].
 | [storage]
Store at RT | [Purification Methods]
Recrystallise thiamphenicol from H2O or CHCl3. The UV has max at 224, 266 and 274nm ( 13,700, 800 and 700) in 95% EtOH. The 1S,2S-isomer [1478651-7] has m 164.3-166.3o (from H2O/EtOAc/pet ether) and [] D 25 -12.6o (c 1, EtOH); and the racemate 1RS,2RS-Racefenical [847-25-6] has m 181-183o (dec) from CHCl3/EtOAc/pet ether. [Cutler et al. J Am Chem Soc 74 5475, 5482 1952, UV: Nachod & Cutler J Am Chem Soc 74 1291 1952, Suter et al. J Am Chem Soc 75 4330 1953, Cutler et al. J Am Pharm Assoc 43 687 1954, Beilstein 13 IV 2957.] | [References]
[1]
Bhaskar, G., Kumar, V. S., Rao, B. V. (2004). A short stereoselective synthesis of (−)-chloramphenicol and (+)-thiamphenicol. Tetrahedron: Asymmetry, 15(8), 1279–1283. https://doi.org/10.1016/j.tetasy.2004.03.007 |
| Questions And Answer | Back Directory | [Description]
Thiamphenicol is a broad-spectrum antibiotic chloramphenicol, which is more effective to the gram-negative bacteria than the gram-positive bacteria. At room temperature, it is a white to off-white crystalline powder or crystal, which can be quickly and completely absorped by oral adminstration, as well as it is excreted mainly in the prototype from the urine for metabolism. It is clinically applied for the treatment of respiratory, urinary tract, liver and gallbladder, typhoid and other intestinal surgery, gynecology and ENT infections. Especially in the mild infections it is more effective. It has the similar chemical structure with the chloramphenicol. Its methyl sulfone substituted the nitro of chloramphenicol, which reduced its toxicity, and in vivo its antibacterial activity is 2.5-5 times stronger than chloramphenicol. For gram-positive bacteria, such as streptococcus pneumoniae and hemolytic streptococcus, it has very strong antibacterial effect, while for gram-negative bacteria, such as Neisseria gonorrhoeae, meningococcus, lung Bacteroides, E. coli, Vibrio cholerae, Shigella and influenza bacillus, it also has strong antibacterial effect. For anaerobic bacteria, Rickettsia and amoeba, it has antibacterial effect in some extent. It has the same antimicrobial mechanism with chloramphenicol, which mainly inhibits the synthesis of bacterial protein. This drug is absorped quickly by oral administration, which reaches peak blood concentration within two hours. Its half-life is 5 hours, that is more longer than chloramphenicol. The bacteria have complete cross resistance to it and chloramphenicol, while the bacteria have some cross-resistance phenomenon to it and tetracycline.
Thiamphenicol also has strong immunosuppressive effects, which is an excellent immunosuppressant. Its mechanism of action have significantly different with other immunosuppressive agents. The immunosuppressive effect is several times higher than the chloramphenicol. It can be as the effective extender for transplantation reaction and surgically allogeneic transplantation.
| [Chemical Properties]
White to off-white crystalline powder or crystal. Melting point (℃) 178-180 (swirled), 164-166 (right-handed).
| [Uses]
It is applied for the treatment of respiratory, urinary tract, liver and gallbladder, typhoid and other intestinal surgery, gynecology and ENT infections. Especially in the mild infections it is more effective.
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