Process for producing optically active 3-quinuclidinol derivativ

Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Preparing heterocyclic carbon compound having only o – n – s,...

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435170, 435171, 435196, 435198, 435220, 435224, 435225, 435913, 435917, 435918, 435921, 435939, 435280, 435121, C12P 1712, C12P 1710

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061210250

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

The present invention relates to a process for producing optically active 3-quinuclidinol derivatives which are very useful compounds as starting materials or intermediates for pharmaceutical preparations, agrochemicals etc.


BACKGROUND ART

Processes for synthesizing racemic 3-quinuclidinol derivatives are widely known according to e.g. Zhur. Obshchi. Khim., 30, 163-71 (1960), Helv. 40, 2107-85 (1957), and J. Am. Chem. Soc. 74, 2215-8 (1952).
On the other hand, processes for synthesizing optically active 3-quinuclidinol derivatives are known as described in e.g. Acta. Pharm. Suec., 16, 281-3 (1979), U.S. Pat. No. 3,997,543, Life sic. 21, 1293-1302 (1977) and U.S. Pat. No. 5,215,918.
The process described in Acta. Pharm. Suec., 16, 281-3 (1979) is a process in which optically active 3-quinuclidinol derivatives are derived by a preferential crystallization method using optically active tartaric acid as a resolution agent, and this prior art process requires the cumbersome procedure that e.g. recrystallization should be repeated several or more times to raise optical purity.
Further, the processes described in U.S. Pat. No. 3,997,543, Life sic. 21, 1293-1302 (1977) and U.S. Pat. No. 5,215,918 report processes for obtaining optically active 3-quinuclidinol derivatives by asymmetrically hydrolyzing lower fatty esters of 3-quinuclidinol with an enzyme. However, the enzyme used in U.S. Pat. No. 3,997,543 and Life sic. 21, 1293-1302 (1977) is a butyryl choline esterase only, and the enzyme used in U.S. Pat. No. 5,215,918 is an only specific enzyme (subtilisin) produced by the genus Bacillus, and thus the type of enzyme used in any of these literatures is limited so these cannot be said to be general processes. There are still not known any other processes for producing optically active 3-quinuclidinol derivatives by means of general enzymes.
Accordingly, the useful process for synthesizing optically active 3-quinuclidinol derivatives, provided by the present invention, has been desired.


DISCLOSURE OF THE INVENTION

Accordingly, the object of the present invention is to provide a process for easily producing optically active 3-quinuclidinol derivatives which are useful intermediates and starting materials for optically active pharmaceutical preparations and optically active agrochemicals.
As a result of their eager study on the process for synthesizing optically active 3-quinuclidinol derivatives, the present inventors found selected enzymes and microorganisms having an activity of optico-selectively hydrolyzing a racemic ester of 3-quinuclidinol, and the present invention was thereby completed.
That is, the present invention relates to a process for producing optically active 3-quinuclidinol or a salt thereof, wherein a racemic 3-quinuclidinol ester represented by the general formula (I): ##STR2## wherein R represents a straight-chain or branched alkyl group, and (H.sup.+) represents that said ester may be in the form of a salt formed with a mineral acid or an organic acid, is reacted with a microorganism belonging to the genus Aspergillus, Rhizopus, Candida or Pseudomonas having the ability to asymmetrically hydrolyze said ester linkage, a culture of said microorganism, a treated material from said microorganism, an enzyme produced by said microorganism, or an enzyme derived from swine or cattle.
Further, the present invention relates to a process for producing optically active 3-quinuclidinol ester or a salt thereof, wherein a racemic 3-quinuclidinol ester represented by the general formula (I): ##STR3## wherein R represents a straight-chain or branched alkyl group, and (H.sup.+) represents that said ester may be in the form of a salt formed with a mineral acid or an organic acid, is reacted with a microorganism belonging to the genus Aspergillus, Rhizopus, Candida or Pseudomonas having the ability to asymmetrically hydrolyze said ester linkage, a culture of said microorganism, a treated material from said microorganism, an enzyme produced by said microorganism, or an enzyme derived from swi

REFERENCES:
patent: 3997543 (1976-12-01), Sokolovsky et al.
patent: 5215918 (1993-06-01), Muchmore
Chemical Abstracts, vol. 97, No. 15, AN 122771a, Oct. 11, 1982.
Chemical Abstracts, vol. 79, No. 5, AN27085z, Aug. 6, 1973.

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