Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Patent
1992-08-21
1994-10-25
Dees, Jose G.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
562445, C07C22912
Patent
active
053591240
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a new .beta.-phenylisoserine derivative of formula: ##STR2## optionally in salt or ester form, to its preparation and to its use.
BACKGROUND OF THE INVENTION
According to E. Kamandi et al., Arch. Pharmaz., 307, 871-878 (1974), it is known to prepare threo-.beta.-phenylisoserine by the action of ammonia on an ester of cis-.beta.-phenylglycidic acid, followed by the action of barytes, in order to avoid racemisation, on the .beta.-phenylisoserine amide obtained as an intermediate.
According to E. Kamandi et al., Arch. Pharmaz., 308, 135-141 (1975), the action of benzylamine on an ester of trans-.beta.-phenylglycidic acid leads to the formation of erythro-N,N'-dibenzyl-.beta.-phenylisoserine amide which, on hydrogenation in the presence of palladium on charcoal, leads to erythro-.beta.-phenylisoserine-N-benzylamide.
DESCRIPTION OF THE INVENTION
According to the invention, the product of formula (I) can be obtained by the action of benzylamine on (2R,3R)-cis-.beta.-phenylglycidic acid, preferably in the form of an alkali metal salt such as the potassium salt or a salt with a nitrogenous base such as benzylamine, the operation being carried out in water at a temperature which is generally between 40.degree. and 100.degree. C.
1 to 40 moles of benzylamine are generally employed per mole of cis-.beta.-phenylglycidic acid.
The product of formula (I), preferably in the form of an alkali metal salt such as the potassium salt, or in the form of a salt with a nitrogenous base such as benzylamine, is obtained after concentrating to dryness the solution obtained.
The product of formula (I) thus obtained can be converted into a (2R,3S)-.beta.-phenylisoserine ester by the action of an alcohol in acidic medium, followed by catalytic hydrogenation, preferably in the presence of palladium on charcoal.
The (2R,3S)-.beta.-phenylisoserine ester is particularly useful for preparing the taxane derivatives of general formula: ##STR3## in which R denotes a hydrogen atom or an acetyl radical and R.sub.1 denotes a phenyl or t-butoxy radical, according to the process described in European Patent Applications EP 0,336,840 or EP 0,336,841.
(2R,3R)-cis-.beta.-Phenylglycidic acid can be prepared under the conditions described by J-N. Denis et al., J. Org. Chem., 51, 46-50 (1986).
The present invention also relates to the product of general formula (II) when it is obtained by a process using the product of formula (I).
The present invention also relates to the pharmaceutical compositions containing a product of general formula (II) when it is obtained by a process using the product of formula (I), in combination with any other pharmaceutically acceptable product, be it inert or physiologically active.
These compositions may be presented in any form which is appropriate to the intended route of administration. The parenteral route is the preferred route of administration, and especially the intravenous route.
The compositions for parenteral administration may be aqueous or nonaqueous sterile solutions, suspensions or emulsions. The solvent or carrier employed may be propylene glycol, vegetable oils, in particular olive oil, and injectable organic esters, for example ethyl oleate. These compositions may also include adjuvants, in particular wetting, emulsifying or dispersing agents. The sterilization may be performed in a number of ways, for example with the aid of a bacteriological filter, by incorporating sterilizing agents in the composition, by irradiation or by heating. They may also be in the form of sterile compositions which may be dissolved or dispersed in sterile water or any other injectable sterile medium.
These compositions are particularly useful in the treatment of acute leukaemia and of solid tumors.
EXAMPLES
The following examples, given without any limitation being implied, show how the invention can be put into practice.
EXAMPLE 1
18.2 g of potassium salt of (2R,3R)-cis-.beta.-phenylglycidic acid (0.09 moles), 65 cm.sup.3 of water and 180 cm.sup.3 of benzy
REFERENCES:
patent: 4240975 (1980-12-01), Umezawa
Chemical Abstract 91:20066h.
Journal of the Chemical Society, Chemical Communications, No. 18, 1988 Sunggak Kim, et al. "A convenient method for beta-lactam formation from beta-amino acids using diphenylphosphinic chloride", pp. 1242-1243 (see p. 1243).
Journal of Organic Chemistry, vol. 51, No. 1, 10 Jan. 1986, Denis et al. "An efficient, enantioselective synthesis of the taxol side chain", pp. 46-50 (see pp. 48-49, cited in the application).
Bulletin Korean Chemical Society, vol. 9, No. 3, Mar, 22, 1988, Sunggak Kim, et al., "A new method for beta.varies.lactam formation from beta-amino acids using benzotriazol-1-yloxytris (dimethylamino) phosphonium hexafluorophosphate", pp. 189-190 (see the whole document).
Archiv der Pharmazie, vol. 307, 1974, Kamandi et al., "Die synthese von beta-phenyloisoserinen durch ammonolyse von beta-phenylglycidestern, I", pp. 871-878, (see the whole document).
Journal of the American Chemical Society, vol. 110, No. 19, Sep. 14, 1988, Holton, et al., "A synthesis of taxusin", pp. 6558-6560.
Journal of the American Chemical Society, vol. 110, No. 17, Aug. 17, 1988, Denis, et al., "A highly efficient, practical approach to natural taxol", pp. 5917-5919 (see p. 5918).
Archiv der Pharmazie, vol. 308, 1975, Kamandi, et al., "Die synthese von beta-phenyl-isoserinen durch ammonolyse von beta-phenylhlycidestern II", pp. 135-141.
Duchesne Jean-Pierre
Mulhauser Michel
Barts Samuel
Dees Jos,e G.
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