Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1998-11-11
2000-02-08
Peselev, Elli
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
536 74, 536 185, C07H 100
Patent
active
060229659
DESCRIPTION:
BRIEF SUMMARY
The invention relates to a new isomerization process for the methyl radical at 10 of erythromycin derivatives
A subject of the invention is an isomerization process characterized in that a compound of formula (I.sub.A): ##STR3## in which either X and Y form together a 3-oxo radical, or X represents a hydrogen atom and Y represents either a radical: ##STR4## in which R.sub.2 represents a hydroxyl radical or an O-acyl radical containing from 2 to 20 carbon atoms, or an O-alkyl radical, containing from 2 to 20 carbon atoms, or an NH.sub.2 radical, atoms, NH(CH.sub.2).sub.n Ar or N.dbd.CH(CH.sub.2).sub.n Ar radical in which n represents an integer comprised between 1 and 6, and Ar represents an optionally substituted aryl or heteroaryl radical, in the form of the 10.alpha. isomer or a mixture of 10.alpha. and 10.beta. isomers, is subjected to the action of a basic agent in order to obtain the corresponding compound of formula (I) in which the methyl radical at 10 is in the .beta. position: ##STR5## and in which R, R.sub.1, X and Y retain their previous meaning and Z' represents a hydrogen atom or an acyl radical containing from 2 to 20 carbon atoms. The acyl radical is preferably an acetyl, propionyl, butyryl, isobutyryl, n-valeryl, isovaleryl, tervaleryl and pivalyl radical, or a benzyl radical. By aryl radical, is preferably meant a phenyl or naphthyl radical, by heteroaryl radical, is meant a radical containing one or more heteroatoms preferably chosen from oxygen, sulphur or nitrogen, it can be one of the following radicals: thienyl, furyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl, thiadiazolyl, pyrazolyl, or isoxazolyl, a pyridyl, pyridazinyl, or pyrazinyl radical, an indolyl, benzofuryl, benzothienyl, quinolinyl or pyridyl-imidazolyl radical. As heteroaryl radical, there can be mentioned for example the radicals: ##STR6##
A more particular subject of the invention is a process characterized in that the operation is carried out in the presence of a basic agent, preferably in a catalytic quantity, Z and Z' representing a hydrogen atom. The basic agent is preferably potash or also a tetraalkylammonium hydroxide for example tetrabutylammonium hydroxide or bromide or DBU (1,8-diazabicyclo [5-4-0]undec-7-ene) or an alkaline carbonate for example sodium or potassium carbonate or soda or tripotassium phosphate or also sodium methylate.
It may be necessary in certain cases to add a phase transfer agent, for example tetrabutyl ammonium bromide.
A quite particular subject of the invention is a process characterized in that the operation is carried out in a solvent which can be for example tetrahydrofuran, 1-methyl 2-pyrrolidonone in aqueous solution, methylene chloride and more particularly an alcohol in particular methanol and in this way the corresponding compound in which Z' represents a hydrogen atom, or an acyl radical containing from 2 to 20 carbon atoms is obtained.
A more particular subject of the invention is: which R represents an NH.sub.2 radical, which R.sub.1 represents a methyl radical, characterized in that X and Y form together a 3-oxo radical, which Z and Z' represent a hydrogen atom.
Therefore, the invention relates to a process which allows the conversion of compounds of formula (I.sub.A) in which the methyl radical at 10 is in the .alpha. position or a mixture of 10.alpha. and 10.beta. into the compounds of formula (I) in which the methyl radical at 10 is in the 10.beta. position. During the formation of the chain in the 11, 12 position a mixture of 10.alpha. and 10.beta. isomers is obtained, therefore if the process described in the Patent EP 676409 is followed, the following reaction is obtained: ##STR7## the product (I.sub.A) obtained is a mixture of .alpha. isomer and .beta. isomer, as indicated in Example 1 of the Patent EP 676409. The 10.beta. product is a product endowed with useful antibiotic properties, it also allows the preparation of other antibiotic products described and claimed in the Patent Application 676409 according to the process: ##STR8##
The compounds endowed with useful a
Benedetti Yannick
Lagouardat Jacques
Scholl Jacques
Hoechst Marion Roussel
Peselev Elli
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