15318-45-3 Usage
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
Different sources of media describe the Chemical Properties of 15318-45-3 differently. You can refer to the following data:
1. White to off-white crystalline powder or crystal. Melting point (℃) 178-180 (swirled), 164-166 (right-handed).
2. Off-White Solid
Uses
Different sources of media describe the Uses of 15318-45-3 differently. You can refer to the following data:
1. 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.
2. Antimicrobial
3. chelating agent, antiseborrheic
4. Thiamphenicol is an antibiotic. Thiamphenicol is the methyl-sulfonyl analogue of chloramphenicol and has a similar spectrum of activity, but is 2.5 to 5 times as potent. Thiamphenicol is used particul
arly for the treatment of sexually transmitted infections and pelvic inflammatory disease.
5. Thiamphenicol is a semi-synthetic chloramphenicol prepared by total synthesis from thiophenol in which the nitro moiety of chloramphenicol is replaced by a methylsulphone, first synthesised at Sterling Winthrop in 1952. Thiamphenicol is a broad spectrum antibiotic with good activity against Gram negative and anaerobic bacteria. Thiamphenicol acts by binding to the 23S sub-unit of the 50S ribosome inhibiting protein synthesis. Thiamphenicol has been extensively studied with over 800 literature citations.
Originator
Thiophenicol,Clin Midy,France,1967
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.
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.]
Check Digit Verification of cas no
The CAS Registry Mumber 15318-45-3 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,5,3,1 and 8 respectively; the second part has 2 digits, 4 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 15318-45:
(7*1)+(6*5)+(5*3)+(4*1)+(3*8)+(2*4)+(1*5)=93
93 % 10 = 3
So 15318-45-3 is a valid CAS Registry Number.
InChI:InChI=1/C12H14Cl2N2O7S/c1-24(21,22)23-6-9(15-12(18)11(13)14)10(17)7-2-4-8(5-3-7)16(19)20/h2-5,9-11,17H,6H2,1H3,(H,15,18)/t9-,10-/m1/s1
15318-45-3Relevant articles and documents
Regioselective preparation of thiamphenicol esters through lipase-catalyzed processes
Da Silva, Marcos R.,Montenegro, Tasso G.C.,De Mattos, Marcos C.,De Oliveira, Maria Da Conceic?a?o F.,De Lemos, Telma L.G.,De Gonzalo, Gonzalo,Lavandera, Iva?n,Gotor-Ferna?ndez, Vicente,Gotor, Vicente
, p. 987 - 994 (2014)
The lipase-catalyzed synthesis of thiamphenicol derivatives has been studied through complementary acylation and hydrolytic approaches, finding Candida antarctica lipase B as the most efficient biocatalyst for the selective modification of both thiampheni
Method for continuously preparing thiamphenicol by using micro-reaction system
-
Paragraph 0021-0043, (2021/08/14)
The invention belongs to the technical field of pharmaceutical engineering, and particularly relates to a method for continuously preparing thiamphenicol by using a micro-reaction system. A micro-reaction system used in the method comprises a micro-mixer, a micro-channel reactor and a back pressure device, and during preparation, a solution of raw materials (1R,2R)-2-amino-1-(4-(methylsulfonyl)phenyl)propane-1,3-diol and an alkaline solution of methyl dichloroacetate are simultaneously injected into the micro-reactor by a pump respectively for condensation reaction, and concentrating, recrystallizing, filtering, washing and drying are conducted on the reaction product to obtain a thiamphenicol product. According to the method provided by the invention, the reaction time is only several minutes, the yield of the product thiamphenicol is greater than 99%, the purity is greater than 99%, the operation is convenient, continuous and controllable, the amplification effect is avoided, the efficiency of the technological process is high, and the method has a very good industrial application prospect.
Unified Strategy to Amphenicol Antibiotics: Asymmetric Synthesis of (-)-Chloramphenicol, (-)-Azidamphenicol, and (+)-Thiamphenicol and Its (+)-3-Floride
Liu, Jinxin,Li, Yaling,Ke, Miaolin,Liu, Minjie,Zhan, Pingping,Xiao, You-Cai,Chen, Fener
, p. 15360 - 15367 (2020/11/30)
The asymmetric synthesis of (-)-chloramphenicol, (-)-azidamphenicol, and (+)-thiamphenicol and its (+)-3-floride, (+)-florfenicol, is reported. This approach toward the amphenicol antibiotic family features two key steps: (1) a cinchona alkaloid derived urea-catalyzed aldol reaction allows highly enantioselective access to oxazolidinone gem-diesters and (2) a continuous flow diastereoselective decarboxylation of thermally stable oxazolidinone gem-diesters to form the desired trans-oxazolidinone monoesters with two adjacent stereocenters that provide the desired privileged scaffolds of syn-vicinal amino alcohols in the amphenicol family.
Florfenicol intermediate synthesis method
-
, (2019/07/04)
The invention belongs to the field of synthesis of pharmaceutical raw materials, and specifically discloses a florfenicol intermediate synthesis method, which comprises: (1) carrying out a reaction ona compound (II) and an acylating reagent in an organic solvent to form a compound (III); (2) carrying out a reaction on the compound (III) and an oxidizing agent in an organic solvent in the presenceof a catalyst to form a compound (IV); (3) carrying out a reaction on the compound (IV) and a fluorinating reagent in an organic solvent to form a compound (V); and (4) carrying out acidolysis on thecompound (V) in an organic solvent, and carrying out deprotection to obtain a compound (I), wherein various groups in the formulas are defined in the specification. According to the present invention, the florfenicol intermediate can be used for preparing florfenicol; and the method has characteristics of novel design, mild conditions and simple operation, and is suitable for industrial production.
