Claims
- 1. A process for the preparation of a (R)-oxyglutaric acid ester derivative of the formula (IV): ##STR23## in which each of R.sup.1 and R.sup.2 independently represents an alkoxy group of 1 to 5 carbon atoms, an aralkyloxy group of 7 to 9 carbon atoms, a halogenated aralkyloxy group of 7 to 9 carbon atoms, or phenyl, R.sup.4 represents a hydroxyl-protecting group, and R.sup.5 represents an alkyl group of 1 to 10 carbon atoms which may have a substituent, comprising the steps of:
- optically resolving a racemate of an oxyglutaric acid mono-ester of the formula (II): ##STR24## in which R.sup.3 represents an alkyl group of 1 to 10 carbon atoms and R.sup.4 has the meanings as defined above to give a (S)-oxyglutaric acid mono-ester of the formula (II),
- reacting a methyl phosphonate derivative or methyl phosphine oxide derivative of the formula (I): ##STR25## in which R.sup.1 and R.sup.2 have the meanings as defined above, with the (S)-oxyglutaric acid mono-ester of the formula (II) to give a (R)-oxyglutaric acid derivative of the formula (III): ##STR26## in which R.sup.1, R.sup.2 and R.sup.4 have the meanings as defined above, and
- converting the isolated (R)-oxyglutaric acid derivative of the formula (III) into the (R)-oxyglutaric acid ester derivative of the formula (IV) using an esterifying reagent having an R.sup.5 group.
- 2. The process of claim 1, wherein the reaction of the methyl phosphonate derivative or methyl phosphine oxide derivative of the formula (I) and the (S)-oxyglutaric acid mono-ester of the formula (II) is performed in an organic solvent in the presence of an alkali metal hexamethyldisilazane of the formula (VI):
- M--N�Si(CH.sub.3).sub.3 !.sub.2 (VI)
- in which M represents an alkali metal.
- 3. The process of claim 1, wherein the step of optically resolving the racemate of an oxyglutaric acid mono-ester of the formula (II) is performed using (S)-(-)-.alpha.-methyl-p-nitrobenzylamine.
- 4. A process for optically resolving a racemate of an oxyglutaric acid mono-ester of the formula (II): ##STR27## in which R.sup.3 represents an alkyl group of 1 to 10 carbon atoms and R.sup.4 is t-butyldimethylsilyl group to recover a (S)-3-t-butyldimethylsilyloxyglutaric acid monoalkyl ester using (S)-(-)-.alpha.-methyl-p-nitrobenzylamine.
Priority Claims (2)
Number |
Date |
Country |
Kind |
5-71970 |
Mar 1993 |
JPX |
|
5-290863 |
Nov 1993 |
JPX |
|
Parent Case Info
This application is a continuation-in-part of Ser. No. 08/218,635, filed Mar. 28, 1994, now abandoned, the contents of which are hereby incorporated by reference
US Referenced Citations (3)
Number |
Name |
Date |
Kind |
4686298 |
Karanewsky et al. |
Aug 1987 |
|
4804770 |
Karanewsky |
Feb 1989 |
|
5177239 |
Singh et al. |
Jan 1993 |
|
Foreign Referenced Citations (1)
Number |
Date |
Country |
554455 |
Aug 1991 |
EPX |
Non-Patent Literature Citations (1)
Entry |
Heathcock et al., J. Chem. Med., 1987, Total Synthesis and Biological Evaluation of Structural Analogues of Compactin and Dihydromevinolin, pp. 1858-1873. |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
218635 |
Mar 1994 |
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