- Preparation of clarithromycin. Selective 6-O-methylation of the novel erythromycin A 9-O-(2-pyrimidyl)oxime
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A new method for the preparation of clarithromycin is described through the highly regioselective O-methylation at C(6)-OH of the novel derivative 9-pyrimidyloxime erythromycin A. The facile synthesis of 6,11-O-dimethyl- and 6,11,12-O-trimethyl erythromycin A is also reported. These compounds are useful as standards to assess clarithromycin purity in quality control processes.
- Brunet, Ernesto,Mu?oz, Dulce María,Parra, Francisco,Mantecón, Susana,Juanes, Olga,Rodríguez-Ubis, Juan Carlos,Carmen Cruzado, Ma,Asensio, Ramón
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Read Online
- A new convenient transformation of erythromycin a into clarithromycin
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Erythromycin A was transformed into clarithromycin by the sequence of reactions: selective thexyldimethylsilylation of the 9-oxime, trimethylsilylation of the 2',4''-hydroxy groups, methylation of the resulting 2',4''-[O-bis(trimethylsilyl)]-9-[O-(dimethylthexylsilyl)oxime] and acidic regeneration of the protected functionalities. Copyright (C) 1999 Elsevier Science Ltd.
- Allevi, Pietro,Longo, Alessandra,Anastasia, Mario
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Read Online
- Process for the preparation of clarithromycin
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The present invention includes a process involving a one-pot reaction for preparing erythromycin 9-oxime salt comprising: (a) reacting erythromycin thiocyanate with an ammonium source to obtain erythromycin free base; (b) oximating the C-9 carbonyl of the erythromycin free base by reacting the erythromycin free base with triethylamine and hydroxyl amine hydrochloride to form erythromycin oxime; and (c) reacting the erythromycin oxime obtained in step (b) with an ammonium source to obtain the erythromycin 9-oxime salt. The present invention is also drawn to a one-pot reaction for preparing clarithromycin starting with the one-pot reaction for preparing erythromycin 9-oxime salt, further comprising after step (c): (d) silylating the hydroxy groups at the oxime group, and the 2′ and 4″ positions of the erythromycin 9-oxime salt to obtain a silylated derivative; (e) methylating the hydroxy group at the 6 position of the silylated derivative using at least one methylating agent in the presence of at least one inorganic base to obtain SMOP, wherein SMOP is 6-O-methyl-2′,4″-bis(trimethylsilyl)-erythromycin A 9-O-(2-methoxyprop-2-yl)oxime; and (f) converting the SMOP into clarithromycin using at least one deoximating agent in the presence of aqueous ethanol.
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Page/Page column 4-6
(2009/04/24)
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- A PROCESS FOR PREPARING CLARITHROMYCIN AND CLARITHROMYCIN INTERMEDIATE
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The present invention discloses a process for preparing Clarithromycin, comprising selectively methylating a 2’,4"-O-bis(trimethylsilyl)eιythromycin A 9-[0-(1-methoxy-1- methylethyl)oxime] of formula (II) with methylating agent comprising methyl iodide, while stirring in the presence of a base and a ternary solvent system.
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Page/Page column 10-13
(2008/06/13)
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- Process to obtain 6-O-methylerythromycin a (clarithromycin)_form II
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The present invention provides a process for the preparation of 6-O-methylerythromycin A Form II comprising treating 6-O-methylerythromycin A with organic acid selected form trifluoroacetic acid, para-toluene sulphonic acid, oxalic acid or acetic acid and converting it into an organic salt of 6-O-methylerythromycin A, which can be neutralized by base to give 6-O-methylerythromycin A Form II.
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Page/Page column 4
(2008/06/13)
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- Process for the preparation of crystalline form II of clarithromycin
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A process for preparing Form II crystals of clarithromycin is provided comprising (a) treating clarithromycin with a carboxylic acid in an organic solvent to provide a clarithromycin acid salt; and, (b) heating the clarithromycin acid salt at a temperature capable of providing Form II crystals of clarithromycin.
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Page/Page column 2
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF CLARITHROMYCIN
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The present invention relates to a process for the production of clarithromycin using solvents with a low toxic potential and water.
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Page/Page column 15-17
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF FORM II CLARITHROMYCIN
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The present invention provides an efficient process for the preparation of polymorphic Form I and II of clarithromycin. The process includes drying wet clarithromycin obtained after purification in the presence of nitrogen gas and in the absence of vacuum. The invention also relates to pharmaceutical compositions that include the Form II of clarithromycin and use of said compositions for treating a condition for which antibiotics are indicated.
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Page/Page column 6
(2008/06/13)
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- Method of treating tuberculosis
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Macrolide and ketolides, and compositions containing the same, useful in the treatment of tuberculosis are disclosed. Methods of treating tuberculosis using the macrolides and ketolides, and compositions containing the same, also are disclosed.
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Page/Page column 27
(2010/02/10)
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- Method of preparing clarithromycin
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Clarithromycin can be easily prepared by reacting erythromycin A N-oxide with a methylating agent to obtain 6-O-methylerythromycin A N-oxide; and treating 6-O-methylerythromycin A N-oxide obtained above with a reducing agent in a high yield.
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Page column 8
(2010/02/08)
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- From (E)- and (Z)-ketoximes to N-sulfenylimines, ketimines or ketones at will. Application to erythromycin derivatives
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Reactions of (E)- and (Z)-ketoximes with trialkylphosphines and diphenyl disulfide (PhSSPh) have been compared to gain insight into the mechanisms involved and their potential applications. N-Sulfenylimine isomers and ketimines have been spectroscopically characterised. Both the E and Z isomers of erythromycin A oxime, when treated with Bu3P and PhSSPh (1:4:8 ratio), give the same N-phenylsulfenyl ketimine (of configuration E) as the major compound, whereas with Bu3P or Me3P and PySeSePy (1:8:4 ratio) afford the imine in good yield. Clarithromycin oxime behaves similarly.
- Esteban, Jorge,Costa, Anna M.,Urpí, Fèlix,Vilarrasa, Jaume
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p. 5563 - 5567
(2007/10/03)
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- CHEMICAL MODIFICATION OF ERYTHROMYCINS. VIII. A NEW EFFECTIVE ROUTE TO CLARITHROMYCIN (6-O-METHYLERYTHROMYCIN A)
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Selective O-methylation of the C-6 hydroxyl group of erythromycin A could be satisfactorily achieved by using its 9-oxime derivatives as the starting materials.Thus, 6-O-methylerythromycin A (clarithromycin) was synthesized from 2'-O-,3'-N-bis(benzyloxycarbonyl)-N-demethylerythromycin A via its 9-oxime derivative by 6 steps.
- Watanabe, Yoshiaki,Adachi, Takashi,Asaka, Toshifumi,Kashimura, Masato,Morimoto, Shigeo
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p. 2121 - 2124
(2007/10/02)
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- The Chemistry od Erythromycin. Reactions of Erythromycin A Imine and its 6-Methyl Ether with Aldehydes and Hydrazines
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Erythromycin imine (3) and its 6-methyl ether (6) are multifunctional N-unsubstituted imines, which, in contrast to most unsubstituted imines, are readily isolable and relatively stable towards hydrolysis.With aldehydes in ethanol, the imines react quite differently: the imine (3) reacts with aliphatic and aromatic aldehydes to give predominantly the 9,11-cyclic imines (9), whereas the ether (6) reacts with aliphatic aldehydes to give N-(1-ethoxyalkyl)imines (13) and with benzaldehyde to give a 9,12-epoxy Schiff's base derivative (12).The imines also differ in their reactivities towards hydrazine derivatives: the imine (3) readily reacts with monosubstituted hydrazines to form erythromycin hydrazone derivatives, whereas the ether (6), in common with erythromycin (1), is unreactive towards these reagents.A rationale for the different modes of reaction of compounds (3) and (6) is discussed.
- Davies, J. Sydney,Hunt, Eric,Zomaya, Iskander I.
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p. 1409 - 1414
(2007/10/02)
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