24729-96-2

Basic information

• Product Name: Clindamycin phosphate
• Synonyms: (2s-trans)-;2-(dihydrogenphosphate;7(s)-chloro-7-deoxylincomycin2-phosphate;cleocinphosphate;dalacinp;l-threo-alpha-d-galacto-octapyranoside,methyl7-chloro-6,7,8-trideoxy-6-(((1-m;u28508;methyl 7-chloro-6,7,8-trideoxy-6-(1-methyl-trans-4-propyl-l-2-pyrrolidinecarboxamido)-1-thio-l-threo-alpha-d-galacto-octopyranoside 2-(dihydrogen phosphate)
• CAS NO: 24729-96-2
• Molecular Formula: C₁₈H₃₄ClN₂O₈PS
• Molecular Weight: 504.97
• EINECS: 246-433-0
• Product Categories: Antibiotics for Research and Experimental Use;Biochemistry;Others (Antibiotics for Research and Experimental Use);API's;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 24729-96-2.mol

Chemical Properties

• Melting Point: 114 °C
• Boiling Point: 159°C
• Appearance: /solid
• Density: 1.41 g/cm³
• Refractive Index: 122 ° (C=1, H2O)
• Storage Temp.: 2-8°C
• Solubility: DMSO: soluble224mg/mL at 25°C
• PKA: pKa 0.964±0.06 (H2O t=21) (Uncertain);6.06 ±0.06 (I=0.008)(H2O t=21) (Uncertain)
• Water Solubility: Freely soluble in water
• Stability: Stable, but store cool. Incompatible with strong oxidizing agents, calcium gluconate, barbiturates, magnesium sulfate, phenytoin
• Merck: 14,2356
• CAS DataBase Reference: Clindamycin phosphate(CAS DataBase Reference)
• NIST Chemistry Reference: Clindamycin phosphate(24729-96-2)
• EPA Substance Registry System: Clindamycin phosphate(24729-96-2)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 22-36/37/38
• Safety Statements: 36-26
• WGK Germany: 3
• RTECS: GF2625000
• Hazardous Substances Data: 24729-96-2(Hazardous Substances Data)

Usage

Indications

Clindamycin Phosphate Topical Solution and Clindamycin Phosphate Lotion (Clindamycin Phosphate Topical Suspension USP, 1%) contain clindamycin phosphate, USP, at a concentration equivalent to 10 mg clindamycin per milliliter. Clindamycin Phosphate Gel contains clindamycin phosphate, USP, at a concentration equivalent to 10 mg clindamycin per gram. Clindamycin Phosphate is indicated for topical application in the treatment of acne vulgaris. In view of the potential for diarrhea, bloody diarrhea and pseudomembranous colitis, the physician should consider whether other agents are more appropriate.

CLINICAL PHARMACOLOGY

Although clindamycin phosphate is inactive in vitro, rapid in vivo hydrolysis converts this compound to the antibacterially active clindamycin. Cross resistance has been demonstrated between clindamycin and lincomycin. Antagonism has been demonstrated between clindamycin and erythromycin. Following multiple topical applications of clindamycin phosphate at a concentration equivalent to 10 mg clindamycin per mL in an isopropyl alcohol and water solution, very low levels of clindamycin are present in the serum (0 to 3 ng/mL) and less than 0.2% of the dose is recovered in urine as clindamycin. Clindamycin activity has been demonstrated in comedones from acne patients. The mean concentration of antibiotic activity in extracted comedones after application of Clindamycin Phosphate Topical Solution for 4 weeks was 597 mcg/g of comedonal material (range 0 to 1,490). Clindamycin in vitro inhibits all Propionibacterium acnes cultures tested (MICs 0.4 mcg/mL). Free fatty acids on the skin surface have been decreased from approximately 14% to 2% following application of clindamycin.

Pharmacokinetics

In an open label, parallel group study of 24 patients with acne vulgaris, once-daily topical administration of approximately 3-12 grams/day of clindamycin phosphate gel for five days resulted in peak plasma clindamycin concentrations that were less than 5.5 ng/ml. Following multiple applications of clindamycin phosphate gel less than 0.04 % of the total dose was excreted in the urine.

Biological Activity

Clindamycin 2-phosphate is an aminoglycoside antibiotic that has been used to study the cytoxicity of antibiotics on human cell lines, Bacterial protein synthesis and peptide translation, and the inhibition of human Tyrosyl-DNA Phosphodiesterase. Clindamycin 2-phosphate is a pharmacological tyrosyl-DNA phosphodiesterase (Tdp1) inhibitor. Clindamycin 2-phosphate can repair DNA topoisomerase I-DNA covalent complexes by hydrolyzing the tyrosyl-DNA bond. It inhibits protein synthesis in bacteria by binding the 50s ribosomal subunit. ? Spectrum of Activity: Gram positive cocci and taxoplasma. Especially active against anaerobic bacteria. Mode of Action: Inhibits protein synthesis in bacterial by binding the 50s ribosomal subunit.

Drug interactions

Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore it should be used with caution in patients receiving such agents.

Incompatibilities

Clindamycin phosphate is incompatible with natural rubber closures. Aminophylline, ampicillin, calcium gluconate, ceftriaxone, ciprofloxacin,doxapram, drotrecogin alfa (activated), fluconazole, magnesium sulfate,phenytoin sodium, ranitidine, tramadol.

Preparation

Preparation of Clindamycin Phosphate: a solution of 808 mg of the phosphorylated ester in 6 ml of pyridine and 16 ml of acetic acid is stirred at ambient temperature while s5 mg of zinc is rapidly added. The mixture is filtered after one hour and evapo rated to a residue which is heated with stirring at 50°C. for 2 hours with a solvent mixture of 2 ml of acetic acid, and 4 ml of 0.5N sulfuric acid. The mixture is cooled and filtered followed by evaporation of the filtrate in vacuo to a residue, which is chromatographed on a suitable ion-exchange resin, in the acid form, and eluted with 2% ammonium hydroxide. The desired product is obtained as ammonium salt by evaporation of the product fractions. (dec. 212°C)

Pharmacology

Clindamycin phosphate is available in 1% concentration in a hydroalcoholic vehicle (30 or 60 mL) as a gel or lotion. Although the drug has not been detected in the blood after topical use, its detection in the urine suggests that 4% to 5% of topically applied clindamycin is absorbed.

Structure and conformation

Semisynthetic derivative of lincomycin.

InChI:InChI=1/C18H34ClN2O8PS/c1-5-6-10-7-11(21(3)8-10)17(24)20-12(9(2)19)15-13(22)14(23)16(18(28-15)31-4)29-30(25,26)27/h9-16,18,22-23H,5-8H2,1-4H3,(H,20,24)(H2,25,26,27)/t9?,10-,11+,12?,13-,14+,15-,16-,18-/m1/s1

Synthetic route

C25H40ClN8O6PS → clindamycin phosphate (24729-96-2)

Conditions	Yield
With hydrogenchloride; acetic acid In water at 50 - 55℃; for 10h;	96.15%

C21H36Cl3N2O7PS → clindamycin phosphate (24729-96-2)

Conditions	Yield
In water at 20℃; for 8h; Temperature; Acidic conditions; Green chemistry;	92%

C35H50ClN2O8PS → clindamycin phosphate (24729-96-2)

Conditions	Yield
Stage #1: C35H50ClN2O8PS With palladium 10% on activated carbon; hydrogen In methanol at 20 - 30℃; under 2585.81 Torr; for 15h; Stage #2: With hydrogenchloride at 60 - 70℃; for 24h; Time;	84.2%

clindamycin hydrochloride (21462-39-5) → clindamycin phosphate (24729-96-2)

lincomycin hydrochloride (859-18-7) → clindamycin phosphate (24729-96-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: phosgene / chloroform; N,N-dimethyl-formamide / 2 h / 5 - 71 °C / Large scale 1.2: 10 °C / Alkaline conditions; Large scale 2.1: toluene-4-sulfonic acid / acetone / 6 h / 35 °C / Large scale 3.1: triethylamine; trichlorophosphate; 1H-imidazole / acetone / 4 h / 22 °C / Large scale 3.2: 30 °C / Large scale View Scheme

C21H37ClN2O5S → clindamycin phosphate (24729-96-2)

Conditions	Yield
Stage #1: C21H37ClN2O5S With 1H-imidazole; triethylamine; trichlorophosphate In acetone at 22℃; for 4h; Large scale; Stage #2: With water In acetone at 30℃; Temperature; Reagent/catalyst; Large scale;

Upstream product

• 859-18-7 lincomycin hydrochloride 
• 147650-54-2 C₂₁H₃₇ClN₂O₅S 
• 13380-36-4 1-methyl-4-propylpyrrolidine-2-carboxylic acid 
• 21462-39-5 clindamycin hydrochloride 

Relevant articles and documents

Synthesis method of clindamycin phosphate and application

The invention belongs to the field of medicine synthesis, and discloses a synthesis method of clindamycin phosphate. The method comprises the following steps: chloridizing tert-butyl (2-chloro-1-(3,4,5-trihydroxy-6-(methylthio) tetrahydro-2H-pyran-2-yl) propyl) carbamate with phosphorus trichloride, esterifying with phosphorus oxychloride, and finally carrying out condensation reaction with 1-methyl-4-propyl pyrrolidine-2-carboxylic acid, so as to obtain the clindamycin phosphate. According to the synthesis method of clindamycin phosphate, molecules with small molecular weight are used as raw materials, so that the purification difficulty of an intermediate is reduced, the recovery rate of the intermediate is improved, and the production cost is reduced. The invention also provides an application of the synthesis method of the clindamycin phosphate, the synthesis method is used for synthesizing the clindamycin phosphate, and the obtained clindamycin phosphate is used for preparing the clindamycin phosphate injection.

Preparation method of clindamycin phosphate

The invention belongs to the technical field of chemical synthesis and relates to a preparation method of clindamycin phosphate. The preparation method includes preparing clindamycin isopropylidene alkali from clindamycin hydrochloride monohydrate, subjecting the clindamycin isopropylidene alkali to phosphate esterification with phosphorus oxychloride as a phosphate esterification agent and 1,2,4-triazole as an acid-binding agent to obtain isopropylidene clindamycin phosphate, and subjecting the isopropylidene clindamycin phosphate to deprotection by hydrolysis of mixed acid to obtain the clindamycin phosphate. The preparation method has the advantages that by preparing the clindamycin phosphate through one-step hydrolysis of organic acid, the preparation method is energy saving and environment friendly; the preparation method is high in yield and low in cost and can obtain the high-purity finished product directly without subsequent refining, so that the molar yield of the clindamycinphosphate can reach 96.15%; the clindamycin phosphate is good in crystal form (bulk density and liquidity), so that aseptic packaging is benefited.

Clindamycin phosphate preparation method

The invention discloses a clindamycin phosphate preparation method. The method sequentially includes steps: adopting clindamycin 3,4-isopropylidene as a raw material, performing reaction with dibenzoxycarbonyl phosphoryl chloride, hydrogenating to remove a benzyl protection group, and finally hydrolyzing under an acidic condition to obtain a product of clindamycin phosphate. Extensive and sufficient material sources, low cost, mild reaction conditions and simple process are realized, each reaction step is conventional in operation, difficulty in purification due to adoption of low-selectivityphosphorus oxychloride is avoided, and a wide application range is realized.

Triazole in the synthesis of clindamycin phosphate in the application of the

The invention relates to an application of tolyltriazole in clindamycin phosphate synthesis. According to the application, pyridine and triethylamine are replaced by the tolyltriazole, so that the tolyltriazole, phosphorus oxychloride and a compound in a first formula can perform phosphate esterification reaction in solvent to obtain a solution of a compound in a second formula. A method for synthesizing the clindamycin phosphate is more efficient, low in cost, economical in energy and environmentally friendly due to the application of the tolyltriazole, and the obtained clindamycin phosphate is high in yield and purity.

A clindamycin phosphate ester synthesis method

The invention belongs to the technical field of chemical synthesis and specifically relates to a synthetic method of clindamycin phosphate. The method comprises the following steps of synthesis of clindamycin free alkali, ketonization reaction, phosphorylation reaction and aftertreatment. According to the invention, the weight yield of the clindamycin phosphate can reach over 80% by changing a charging sequence, steps and a catalyst.

Clindamycin-2-phosphoryl benzylate

A novel compound, also known as 7(s)-chloro-7-deoxylincomycin-2-phosphoryl benzylate, useful an an intermediate in the production of the antibiotic, clindamycin-2-phosphate.