Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Preparing heterocyclic carbon compound having only o – n – s,...
Reexamination Certificate
1999-06-21
2001-07-03
Saucier, Sandra E. (Department: 1651)
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Preparing heterocyclic carbon compound having only o, n, s,...
C435S280000
Reexamination Certificate
active
06255087
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to a process for preparing enantiomerically pure alcohols.
Reductions with microorganisms or enzymes are described in a large number of pulications and patents. Only a few studies have been published on the reduction of ketones with heteroaromatic radicals and specifically with heteroaromatic radicals in the position a to the carbonyl group.
Thus, for example, Davis et al. (Appl. Environ. Microbiol. 48 (1984) 327-331) describe the microbial reduction of pentoxifylline (3,7-dihydro-3,7-dimethyl-1-(5-oxohexyl)-1H-purine-2,6-dione), a ketone with a heterocycle in the position &ggr; to the carbonyl group, to the corresponding alcohol (3,7-dihydro-3,7-dimethyl-1-(S-hydroxyhexyl)-1H-purine-2,6-dione). Sources of carbon, nitrogen and phosphorus are necessary for reduction with growing microorganisms. Nothing is said about the enantiomeric purity of the resulting alcohol.
Imuta et al. (J. Org. Chem. 43 (1978) 3530-3532) likewise describe the synthesis in moderate yields and enantiomeric purities of pyridylethanol from the corresponding ketones using growing Cryptococcus macerans cultures. Sources of carbon and nitrogen are also necessary for the reduction in this case.
Takeshita et al. describe in Heterocycles 26 (1987) 3051-3054, the reduction of acetylpyridines with Saccharomyces cerevisiae to pyridylethanol in poor yields.
Optimal microbial reduction of ketones should advantageously comply with a number of conditions such as:
1. high enantiomeric purity
2. high chemical yield
3. high selectivity of the enzyme or microorganism
4. small amounts of catalyst (amounts of enzyme or microorganism)
5. good solubility of precursor and product under the reaction conditions
6. good space-time yield
7. easy purification of the products
8. low-cost synthesis
DETAILED DESCRIPTION OF THE INVENTION
WO 95/10521 claims the chemical synthesis of 1,2,4-triazolo[1,5-a]pyrimidines and the use thereof in pharmaceutical preparations.
It is an object of the present invention to develop a stereoselective synthesis of intermediates of 1,2,4-triazolo[1,5-a]pyrimidines which provides these compounds advantageously with high optical purities and good chemical yields and allows the products to be worked up easily.
We have found that this object is achieved by a process for preparing enantiomerically pure alcohols of the formula I (Ia or Ib)
where the substituents have the following meanings:
R
1
hydrogen or substituted or unsubstituted C
1
-C
6
-alkyl, C
1
-C
6
-alkoxy or C
1
-C
6
-alkanoyl,
R
2
and R
3
independently of one another hydrogen or substituted or unsubstituted C
1
-C
6
-alkyl, C
1
-C
6
-alkoxy, C
1
-C
6
-alkanoyl, C
1
-C
6
-alkylthio, C
1
-C
6
-alkylsulfinyl or C
1
-C
6
-alkylsulfonyl,
R
4
substituted or unsubstituted C
1
-C
6
-alkyl, C
3
-C
8
-cycloalkyl,
which comprises reducing compounds of the formula II where the substituents R
1
to R
4
have the abovementioned meanings
in aqueous solution in the presence of a carbon source and of a microorganism or of a reducing agent, of a cofactor and of an enzyme, to compounds of the formula I.
R
1
in formulae I and II is hydrogen or substituted or unsubstituted C
1
-C
6
-alkyl, C
1
-C
6
-alkoxy or C
1
-C
6
-alkanoyl.
The radicals mentioned for R
1
have the following meanings, for example:
alkyl branched or unbranched C
1
-C
6
-alkyl chains such as methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl or 1-ethyl-2-methylpropyl,
alkoxy branched or unbranched C
1
-C
6
-alkoxy chains such as methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy, 1,1-dimethylethoxy, pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, hexoxy, 1-methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4-methylpentoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethylbutoxy, 2-ethylbutoxy, 1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxy or 1-ethyl-2-methylpropoxy,
alkanoyl branched or unbranched C
1
-C
6
-alkanoyl chains such as methanoyl, ethanoyl, propanoyl, 1-methylethanoyl, butanoyl, 1-methylpropanoyl, 2-methylpropanoyl, 1,1-dimethylethanoyl, pentanoyl, 1-methylbutanoyl, 2-methylbutanoyl, 3-methylbutanoyl, 1,1-dimethylpropanoyl, 1,2-dimethylpropanoyl, 2,2-dimethylpropanoyl, 1-ethylpropanoyl, hexanoyl, 1-methylpentanoyl, 1,2-methylpentanoyl, 3-methylpentanoyl, 4-methylpentanoyl, 1,1-dimethylbutanoyl, 1,2-dimethylbutanoyl, 1,3-dimethylbutanoyl, 2,2-dimethylbutanoyl, 2,3-dimethylbutanoyl, 3,3-dimethylbutanoyl, 1-ethylbutanoyl, 2-ethylbutanoyl, 1,1,2-trimethylpropanoyl, 1,2,2-trimethylpropanoyl, 1-ethyl-1-methylpropanoyl and 1-ethyl-2-methylpropanoyl.
Suitable substituents for the alkyl, alkoxy or alkanoyl radicals mentioned for R
1
are one or more substituents such as halogen, such as fluorine, chlorine, bromine, cyano, nitro, amino, mercapto, alkyl, alkoxy or aryl.
R
2
and R
3
in the formulae I and II are, independently of one another, hydrogen or substituted or unsubstituted C
1
-C
6
-alkyl, C
1
-C
6
-alkoxy, C
1
-C
6
-alkanoyl, C
1
-C
6
-alkylthio, C
1
-C
6
-alkylsulfinyl or C
1
-C
6
-alkylsulfonyl.
The radicals mentioned for R
2
and R
3
have the following meanings, for example:
alkyl branched or unbranched C
1
-C
6
-alkyl chains such as methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl or 1-ethyl-2-methylpropyl,
alkoxy branched or unbranched C
1
-C
6
-alkoxy chains such as methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy, 1,1-dimethylethoxy, pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, hexoxy, 1-methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4-methylpentoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethylbutoxy, 2-ethylbutoxy, 1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxy or 1-ethyl-2-methylpropoxy,
alkanoyl branched or unbranched C
1
-C
6
-alkanoyl chains such as methanoyl, ethanoyl, propanoyl, 1-methylethanoyl, butanoyl, 1-methylpropanoyl, 2-methylpropanoyl, 1,1-dimethylethanoyl, pentanoyl, 1-methylbutanoyl, 2-methylbutanoyl, 3-methylbutanoyl, 1,1-dimethylpropanoyl, 1,2-dimethylpropanoyl, 2,2-dimethylpropanoyl, 1-ethylpropanoyl, hexanoyl, 1-methylpentanoyl, 1,2-methylpentanoyl, 3-methylpentanoyl, 4-methylpentanoyl, 1,1-dimethylbutanoyl, 1,2-dimethylbutanoyl, 1,3-dimethylbutanoyl, 2,2-dimethylbutanoyl, 2,3-dimethylbutanoyl, 3,3-dimethylbutanoyl, 1-ethylbutanoyl, 2-ethylbutanoyl, 1,1,2-trimethylpropanoyl, 1,2,2-trimethylpropanoyl, 1-ethyl-1-methylpropanoyl and 1-ethyl-2-methylpropanoyl,
alkylthio branched or unbranched C
1
-C
6
-alkylthio chains such as methylthio, ethylthio, n-propylthio, 1-methylethylthio, n-butylthio, 1-methylpropylthio, 2-methylpropylthio, 1,1-dimethylethylthio, n-pentylthio, 1-methylbutylthio, 2-methylbutylthio, 3-methylbutylthio, 2,2-dimethylpropylthio, 1-ethylpropylthio, n-hexylthio, 1,1-dimethylpropy
Dingler Christoph
Holman Nicholas John
BASF - Aktiengesellschaft
Keil & Weinkauf
Saucier Sandra E.
LandOfFree
Method for producing alcohols free of enantiomers does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for producing alcohols free of enantiomers, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for producing alcohols free of enantiomers will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2502561