Process for the stereoselective preparation of phenylisoserine derivatives used in making taxols
AssigneeRhone-Poulenc Rorer S.A.
InventorsArlene Correa, Jean-Noel Denis, Andrew-Elliot Greene
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Abstract
A stereoselective process for preparing phenylisoserine derivatives is disclosed. Benzylamine is reacted with an agent for introducing a phenyl or a t-butoxycarbonyl group. The product undergoes double anionization and then is reacted with acrolein to provide a mixture of alcohol syn and anti diasteroisomers. The syn isomer is isolated by chromatography. Whereupon, the hydroxyl is protected and the product is oxidized to provide the phenylisoserine derivative.
Claims10
Process for the stereoselective preparation of phenylisoserine derivatives of formula ##STR7## in which R is a phenyl or tert-butoxy radical and R.sub.1 is a protecting group for the hydroxyl group, comprising treating benzylamine with an agent for introducing a benzoyl or t-butoxycarbonyl group to give the product of formula ##STR8## which, after double anionization, is reacted with acrolein to give the alcohol of formula ##STR9## in the form of a syn and anti mixture, from which the syn form:
- ##STR10## is separated, the hydroxyl group of said syn form is protected and the alcohol protected in this way is then oxidized to give the phenylisoserine derivative of formula (I) in the syn form, which is optionally separated into enantiomers.
Process for the preparation of baccatin III and 10-deacetylbaccatin III derivatives of formula ##STR11## in which R is a phenyl radical or a tert-butoxy radical and R.sub.2 is a hydrogen atom or an acetyl radical, comprising treating benzylamine with an agent for introducing a benzoyl or t-butoxycarbonyl group, to obtain the product of formula ##STR12## which, after double anionization, is reacted with acrolein to give the alcohol of the formula ##STR13## in the form of a syn and anti mixture, from which the syn form:
- ##STR14## is separated, the hydroxyl group of said syn form is protected and the alcohol protected in this way is then oxidized to give the phenylisoserine derivative of formula:
- ##STR15## in which R.sub.1 is a protecting group for the hydroxyl group, in the syn form, the enantiomers of which are optionally separated, and which is reacted with a taxane derivative of formula ##STR16## in which R.sub.3 is an acetyl radical or a protecting group for the hydroxyl group and R.sub.4 is a protecting group for the hydroxyl group, and then the product of formula (II) is isolated after replacing the protecting groups R.sub.1 and R.sub.4 with hydrogen atoms and optionally replacing R.sub.3 with a hydrogen atom.
Dependencies are inferred from the claim text.