Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Patent
1994-09-26
1997-03-04
Geist, Gary
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
548952, 560 28, 560 29, 562444, C07C22934, C07D20502
Patent
active
056081022
DESCRIPTION:
BRIEF SUMMARY
DESCRIPTION OF THE INVENTION
This application is a 371 PCT/FR93/0024, filed Mar. 8, 1993.
The present invention relates to new process for the preparation of .beta.-phenylisoserine and its analogues of general formula: ##STR2## which are particularly useful for preparing taxane derivatives which have remarkable antitumor and antileukaemic activities.
In the general formula (I), Ar represents an aryl radical and R represents a hydrogen atom or an alkyl radical containing 1 to 4 carbon atoms, which is optionally substituted by a phenyl radical, or a phenyl radical.
Preferably, Ar represents a phenyl or an .alpha.- or .beta.-naphthyl radical which is optionally substituted by one or more atoms or radicals chosen from halogen atoms (fluorine, chlorine, bromine, iodine) and alkyl, aryl, aralkyl, alkoxy, alkylthio, aryloxy, arylthio, hydroxy, hydroxyalkyl, mercapto, formyl, acylamino, aroylamino, alkoxycarbonylamino, amino, alkylamino, dialkylamino, carboxy, alkoxycarbonyl, carbamoyl, dialkylcarbamoyl, cyano, nitro and trifluoromethyl radicals, it being understood that the alkyl radicals and the alkyl portions of the other radicals contain 1 to 4 carbon atoms and that the aryl radicals are phenyl or .alpha.- or .beta.-naphthyl radicals.
More particularly, Ar represents a phenyl radical which is optionally substituted by one or more atoms or radicals, which are identical or different, chosen from halogen atoms and alkyl, alkoxy, amino, alkylamino, dialkylamino, acylamino, alkoxycarbonylamino and trifluoromethyl radicals.
Still more particularly, Ar represents a phenyl radical which is optionally substituted by a chlorine or fluorine atom or by an alkyl (methyl), alkoxy (methoxy), dialkylamino (dimethylamino) or acylamino (acetylamino) radical.
It is known to prepare .beta.-phenylisoserine by hydrolysis of a lactam under the conditions described by C. Palomo et al., Tetrahedron Letters, 31, 6429-6439 (1990).
Threo-.beta.-phenylisoserine can be obtained by the action of ammonia on a cis-.beta.-phenylglycidic acid ester followed by the action of baryta, so as to avoid racemization on the .beta.-phenylisoserine amide obtained as an intermediate under the conditions described by E. Kamandi et al., Arch. Pharmaj., 307 871-878 (1974).
The .beta.-phenylisoserine can also be obtained under the conditions described in International Application PCT WO-A-91/13053 by passing via N-benzyl-.beta.-phenylisoserine. portion contains 1 to 4 carbon atoms or nitro radicals. More particularly, Ph represents a phenyl radical which is optionally substituted by one or more radicals, which are identical or different, chosen from methoxy, methylthio, methylamino, dimethylamino or nitro radicals.
Generally, the hydrogenolysis is performed by means of hydrogen in the presence of a catalyst.
More particularly, a palladium on carbon containing 1 to 10% by weight of palladium or palladium dihydroxide on carbon containing up to 10% by weight of palladium are used as catalyst.
The hydrogenolysis is performed in an organic solvent or a mixture of organic solvents.
It is particularly advantageous to carry out the procedure in acetic acid optionally combined with an aliphatic alcohol containing 1 to 4 carbon atoms. A mixture of acetic acid and methanol is of a very special interest.
According to a preferred embodiment of the process, the procedure is carried out under a hydrogen pressure which may be between 1 and 50 bars.
The temperature for carrying out the process is generally between 20.degree. and 80.degree. C. and preferably between 50.degree. and 70.degree. C.
The hydrogen required for the hydrogenolysis may also be provided by a compound which releases hydrogen by chemical reaction or by thermal decomposition such as ammonium formate.
The product of general formula (II) may be obtained by hydrolysis or alcoholysis of a product of general formula: ##STR3## in which Ar and Ph are defined as above.
It is particularly advantageous to carry out an alcoholysis by means of an alcohol of general formula R--OH in which R is defined as above, the pro
REFERENCES:
patent: 4924012 (1990-05-01), Colin et al.
patent: 5041643 (1991-08-01), Tinti et al.
patent: 5175315 (1992-12-01), Holton
patent: 5294737 (1994-03-01), Ojima
patent: 5304670 (1994-04-01), Correa et al.
I. Ojima et al., "Azetidines and Bisazetidines. Their Synthesis and Use as the Key Intermediates to Enantiomerically Pure Diamines, Amino Alcohols, and Polyamines". Journal of Organic Chemistry vol. 56, No. 18 (1991) pp. 5263-5277.
Tetrahedron Letters, vol. 31, No. 44, 1990, pp. 6429-6432; C. Palomo et al. "Highly Stereoselective Synthesis of alpha-hydroxy beta-amino acids through beta-lactams: application to the Synethesis of the Taxol and Bestatin Side Chains and Related Systems".
Bourzat Jean-Dominique
Commer.cedilla.on Alain
Frazier Barbara S.
Geist Gary
Rhone-Poulenc Rorer S.A.
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