This title appears in the Scientific Report :
2001
Please use the identifier:
http://dx.doi.org/10.1002/1521-3765(20011105)7:21<4562::AID-CHEM4562>3.0.CO;2-4 in citations.
Biocatalytic reduction of beta,delta-diketo esters : a highly stereoselective approach to all four stereoisomers of a chlorinated beta,delta-dihydroxy hexanoate
Biocatalytic reduction of beta,delta-diketo esters : a highly stereoselective approach to all four stereoisomers of a chlorinated beta,delta-dihydroxy hexanoate
A stereoselective chemoenzymatic synthesis of all four stereoisomers of tert-butyl 6-chloro-3,5-dihydroxyhexanoate (6a) is presented. The key step of the sequence is a highly regio- and enantioselective single-site reduction of tert-butyl 6-chloro-3,5-dioxohexanoate (1 a) by two enantiocomplementary...
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Personal Name(s): | Wolberg, M. |
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Hummel, W. / Müller, M. | |
Contributing Institute: |
Biotechnologie 2; IBT-2 |
Published in: | Chemistry, 7 (2001) S. 4562 - 4571 |
Imprint: |
Weinheim
Wiley-VCH
2001
|
Physical Description: |
4562 - 4571 |
DOI: |
10.1002/1521-3765(20011105)7:21<4562::AID-CHEM4562>3.0.CO;2-4 |
Document Type: |
Journal Article |
Research Program: |
Verfahrenstechnik zur mikrobiellen Gewinnung von Primärmetaboliten |
Series Title: |
Chemistry-a European Journal
21 |
Subject (ZB): | |
Publikationsportal JuSER |
A stereoselective chemoenzymatic synthesis of all four stereoisomers of tert-butyl 6-chloro-3,5-dihydroxyhexanoate (6a) is presented. The key step of the sequence is a highly regio- and enantioselective single-site reduction of tert-butyl 6-chloro-3,5-dioxohexanoate (1 a) by two enantiocomplementary biocatalysts. Alcohol dehydrogenase from Lactobacillus brevis (recLBADH) afforded a 72% yield of enantiopure tert-butyl (S)-6-chloro-5-hydroxy-3-oxohexanoate [(S)-2a]. The enantiomer (R)-2a was prepared with 90-94% ee by Baker's yeast reduction in a biphasic system (50% yield). Both biotransformations were performed on a gram scale. The P-keto group of the enantiomeric delta -hydroxy-beta -keto esters 2a thus obtained was reduced by syn- and anti-selective borohydride reductions. Permutation of the reduction methods yielded all four stereoisomers of the crystalline target compound 6a (greater than or equal to 99.3% ce, dr greater than or equal to 205:1), which is a versatile 1,3-diol building block. recLBADH accepts a variety of beta,delta -diketo esters as was determined in a photometric assay. tert-Butyl 3,5-dioxohexanoate (1b) and tert-butyl 3,5-dioxoheptanoate (1c) were reduced on a preparative scale as well to afford the corresponding delta -hydroxy-beta -keto esters (R)-2b and (R)-2c with 99.4% ee and 98.1 % ee, respectively. |