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Production of Chiral Aminoalcohols

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: N/A
Agency Tracking Number: 2R44GM060822-02
Amount: $0.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: N/A
Solicitation Number: N/A
Timeline
Solicitation Year: N/A
Award Year: 2001
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
39 CONGRESS ST, STE 303
PASADENA, CA 91105
United States
DUNS: N/A
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 J ROZZELL
 () -
Business Contact
Phone: (818) 841-0072
Email: DAVIDROZZELL@BIOCATALYTICS.COM
Research Institution
N/A
Abstract

DESCRIPTION (provided by applicant): In Phase 1, the enzymatic reduction step
for stereoselective synthesis of chiral vicinal aminoalcohols was established.
Eight different ketoreductases were evaluated, including 5 ketoreductases that
were cloned and expressed during this project, and the enzymes were
characterized for substrate and stereochemical preferences. Reduction of
2-substituted-beta-ketoesters, the key precursors for chiral aminoalcohols,
gave products of high enantioselectivity and diastereoselectivity. Recycle
numbers for nicotinamide cofactors of more than 5000 were achieved, leading to
favorable economic projections. In Phase 2 we will create a library of
stereoselective ketoreductase enzymes by mutagenizing cloned genes, enabling
the stereoselective reduction of beta-ketoesters spanning a broad structural
range. A cloning host will be developed that eliminates the need for antibiotic
resistance for plasmid maintenance, and production of ketoreductase enzymes
will be demonstrated in laboratory-scale fermentors. Reaction conditions will
be optimized using two-phase aqueous-organic systems to maximize volumetric
productivity for ketones that have limited solubility in water. The chemical
rearrangement to produce the aminoalcohol products will be demonstrated, and a
procedure based on the use of metal-affinity resins will be developed for
recovering the aminoalcohol products from the reaction milieu. Three
commercially important chiral vicinal aminoalcohols will be produced in
multi-gram amounts to demonstrate the overall technology.
PROPOSED COMMERCIAL APPLICATION:
Production of key intermeidates for the production of existing and new pharmaceutical
products.

* Information listed above is at the time of submission. *

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