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US 5,225,339 AGranted
Lactobacillus kefir alcohol dehydrogenase
AssigneeThe Scripps Research Institute
InventorsChi-Huey Wong, Curt W. Bradshaw
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Abstract
The present invention discloses the preparation of R-configured trialkylsilylethynyl .alpha.-alcohols from similarly substituted .alpha.-ketones, and vice versa, catalyzed by the alcohol dehydrogenase of Lactobacillus kefir, ATCC No. 35411. Also disclosed is the acceptance or transfer of a hydride ion from or to the pro-R face of NADPH or NADP, respectively, as catalyzed by that enzyme.
Claims21
A process for the preparation of a trialkylsilylethynyl .alpha.-alcohol of R-configuration comprising:
- (a) forming a reaction mixture in a liquid medium by admixing (i) NADPH, (ii) a catalytic amount of the alcohol dehydrogenase enzyme,, from Lactobacillus kefir, ATCC designation 35411, and (iii) a trialkylsilylethynyl .alpha.-ketone of formula I, below:
- ##STR82## wherein R is selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkenyl, C.sub.1 -C.sub.6 haloalkyl and C.sub.1 -C.sub.3 alkyl C.sub.1 -C.sub.3 alkylenecarboxylate, and whose chain length is that of one to about six carbon atoms;
- and
- R.sup.1, R.sup.2 and R.sup.3 are the same or different, and each is selected from the group consisting of C.sub.1 -C.sub.6 alkyl;
- and
- (b) maintaining said reaction mixture under biological reaction conditions and for a time period sufficient to reduce said silicon-containing ketone and form said silicon-containing alcohol of the corresponding formula.
3 more elements
A process for the preparation of a trialkylsilylethynyl .alpha.-ketone comprising
- (a) forming a reaction mixture in a liquid medium by admixing (i) NADP, (ii) a catalytic amount of the alcohol dehydrogenase enzyme from Lactobacillus kefir, ATCC designation 35411, and (iii) an R-configured trialkylsilylethynyl .alpha.-alcohol of formula Ia, below:
- ##STR90## wherein R is selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkenyl, C.sub.1 -C.sub.6 haloalkyl and C.sub.1 -C.sub.3 alkyl C.sub.1 -C.sub.3 alkylenecarboxylate, and whose chain length is that of one to about six carbon atoms;
- and
- R.sup.1, R.sup.2 and R.sup.3 are the same or different, and each is selected from the group consisting of C.sub.1 -C.sub.4 alkyl;
- and
- (b) maintaining said reaction mixture under biological reaction conditions and for a time period sufficient to oxidize said silicon-containing alcohol and form said silicon-containing ketone of the corresponding formula.
3 more elements
A process for transferring a hydride ion from an R-alcohol to the pro-R position of NADP comprising
- (a) forming a reaction mixture in a liquid medium by admixing (i) NADP, (ii) a catalytic amount of the alcohol dehydrogenase enzyme, from Lactobacillus kefir, ATCC designation 35411, and (iii) an R-alcohol of formula II, below:
- ##STR91## wherein R.sup.5 is selected from the group consisting of phenyl, furanyl, thiophenyl, pyridyl, indoyl, biphenylyl, C.sub.1 -C.sub.3 alkylenephenyl, C.sub.2 -C.sub.3 alkenylenephenyl, C.sub.2 -C.sub.3 oxaalkylenephenyl, C.sub.1 -C.sub.6 alkenyl, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 haloalkyl, C.sub.1 -C.sub.6 oxoalkyl, C.sub.1 -C.sub.6 halooxoalkyl, and C.sub.1 -C.sub.3 alkylenecarboxylate;
- R.sup.4 is C.sub.1 -C.sub.4 trialkylsilylethynyl;
- or R.sup.4 and R.sup.5 together form a 5-, 6- or 7-membered saturated or monoethylenically unsaturated ring;
- R.sup.6 is hydrogen, deuterium or tritium;
- the total chain length of a substrate of formula II is three to about 10 carbon atoms;
- and
- (b) maintaining said reaction mixture under biological conditions and for a time period sufficient to transfer said hydride ion from said R-configured alcohol to NADP and form NADPH and a ketone of the corresponding formula.
5 more elements
A process for transferring a hydride ion from the pro-R position of NADPH to the si face of a carbonyl group of a ketone comprising
- (a) forming a reaction mixture by admixing in a liquid medium (i) NADPH, (ii) a catalytic amount of the alcohol dehydrogenase enzyme from Lactobacillus kefir, ATCC designation 35411, and (iii) a ketone of the formula IIa, below:
- ##STR92## wherein R.sup.5 is selected from the group consisting of phenyl, furanyl, thiophenyl, pyridyl, indoyl, biphenylyl, C.sub.1 -C.sub.3 alkylenephenyl, C.sub.2 -C.sub.3 alkenylenephenyl, C.sub.2 -C.sub.3 oxaalkylenephenyl, C.sub.1 -C.sub.6 alkenyl, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 haloalkyl, C.sub.1 -C.sub.6 oxoalkyl, C.sub.1 -C.sub.6 halooxoalkyl, and C.sub.1 -C.sub.3 alkylenecarboxylate;
- R.sup.6 is C.sub.1 -C.sub.4 trialkylsilylethnynyl, C1-C6 azaalkyl, C1-C6 oxoalkyl, C1-C6 alkoxy carbonyl, C1-C6 acyl and C1-C6 oxoalkyl;
- or R.sup.4 and R.sup.5 together form a 5-, 6- or 7-membered saturated or monoethylenically unsaturated ring;
- the total chain length of a substrate of formula II is three to about 10 carbon atoms;
- and
- (b) maintaining said reaction mixture under biological conditions and for a time period sufficient to transfer a hydride ion from said pro-R position of NADPH to said si face of said carbonyl group of said ketone and form NADP and an R-configured alcohol of the corresponding formula.
4 more elements
Dependencies are inferred from the claim text.