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US 6,800,477 B2Granted
Stereoselective reduction of substituted acetophenone
AssigneeBristol-Myers Squibb Company
InventorsRamesh Patel, Animesh Goswami, Linda N. Chu, Venkata B. Nanduri, Steven L. Goldberg, Robert M. Johnston, Mary Jo Donovan, K. David Mirfakhrae
Life of this patent
Estimating the term…
Abstract
The present invention is directed to novel stereoselective processes for the preparation of (S)-1-arylethanols by the reduction of the corresponding keto group containing compounds by microorganisms. (S)-1-arylethanols are useful as intermediates in the synthesis of compounds that are inhibitors of γ-secretase useful in the treatment of Alzheimer's disease.
Claims9
A process for the preparation of a compound of Formula (I)
- Wherein
- X is F, Cl, I or R1;
- Cl, Br, I or R1;
- R1 is substituted or unsubstituted alkyl, alkenyl or (CH2)nCOR2;
- n is an integer from 1 to 10;
- R2 is OH, OR3 or NH2;
- and
- R3 is substituted or unsubstituted alkyl, alkenyl, C3-7cycloalkyl or substituted or unsubstituted aryl;
- by stereoselective reduction of a compound of Formula (II)
- wherein
- X Is F, Cl, Br or I;
- and
- Cl, Br, I or R1;
- R1 is substituted or unsubstituted alkyl, alkenyl, or (CH2)nCOR2;
- n is an integer from 1 to 10;
- R2 is OH, OR3 or NH2;
- and
- R9 is substituted or unsubstituted alkyl, alkenyl, C3-7cycloalkyl or substituted or unsubstituted aryl;
- by reaction with an oxidoreductase enzyme capable of catalyzing the enzymatic reduction of ketones represented by Formula (II), wherein said oxidoreductase enzyme is the Pichia methanoilca ketoreductase of SEQ ID NO. 7 as expressed in Eschericha Coli.
16 more elements
A process for the preparation of a compound of Formula (I)
- wherein
- X is F, Cl, Br, I or R1;
- and
- Cl, Br, I or R1;
- R1 is substituted or unsubstituted alkyl, alkenyl, or (CH2)nCOR2,
- n is an integer from 1 to 10;
- R2 is OH, OR3 or NH2;
- and
- R3 is substituted or unsubstituted alkyl, alkenyl, C3-7cycloalkyl or substituted or unsubstituted aryl;
- by stereoselective reduction of a compound of Formula (II)
- wherein
- X is F, Cl, Br, I or R1;
- and
- Cl, Br, I, or R1;
- R1 is substituted or unsubstituted alkyl, alkenyl or (CH2)nCOR2;
- n is an integer from 1 to 10;
- R2 is OH, OR3 or NH2;
- and
- R3 is substituted or unsubstituted alkyl, alkenyl,
- C3-7 cyoloalkyl or substituted or unsubstituted aryl;
- comprising reacting said compound of Formula (II) with a microorganism that supplies an oxidoreductase enzyme capable of catalyzing the enzymatic reduction of ketones represented by Formula (II), wherein the microorganism Is Candida sonorensis, Candida boidini, Candida guilliermondi, Candida utilis, Candida maltosa, Candida kefir, Candida parapslosis, Geotrichum candidum, Rhodotorula glutinis, Hansenula fabianii, Hansenula polymorpha, Hansenula saturnus, Nocardia salmonicolor, Pichia anomala, Pichia capsulata, Pichia membranafaciens, Pichia methanolica, Pichia pinus, Pichia silvicola, Pichia stipitis, Sphingomonas paucimobilis, Saccharomyces cerevisiae, Yeast, and Baker's Yeast.
18 more elements
Dependencies are inferred from the claim text.