- Large-scale synthesis of new pyranoid building blocks based on aldolase-catalysed carbon-carbon bond formation
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A new large-scale approach to the synthetically versatile chloromethyl-substituted, α,β-unsaturated δ-lactone 3 is described. The synthesis is based on a biocatalytic process performed on an industrial scale. Conjugate addition of C-, N-, O-, and S-nucleophiles to lactone 3 affords a variety of new pyranoid building blocks in a highly diastereoselective manner. The operational simplicity of the whole sequence allows for preparing these building blocks on an attractive scale.
- Wolberg, Michael,Dassen, Ben H. N.,Schuermann, Martin,Jennewein, Stefan,Wubbolts, Marcel G.,Schoemaker, Hans E.,Mink, Daniel
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experimental part
p. 1751 - 1759
(2009/07/25)
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- Biocatalytic reduction of β,δ-diketo esters: A highly stereoselective approach to all four stereoisomers of a chlorinated β,δ-dihydroxy hexanoate
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A stereoselective chemoenzymatic synthesis of all four stereoisomers of tert-bulyl 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 (1a) by two enantiocomplementary biocatalysts. Alcohol dehydrogenase from Lactobacillus brevis (recLBADH) afforded a 72% yield of enantiopure tert-butyl (5)-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 β-keto group of the enantiomeric δ-hydroxy-β-keto esters 2a thus obtained was reduced by synand anti-selective borohydride reductions. Permutation of the reduction methods yielded all four stereoisomers of the crystalline target compound 6a (≥99.3% ee, dr≥205:1), which is a versatile 1,3-diol building block. recLBADH accepts a variety of β,δ-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 δ-hydroxy-β-keto esters (R)-2b and (R)-2c with 99.4% ee and 98.1% ee, respectively. Wiley-VCH Verlag GmbH, 2001.
- Wolberg, Michael,Hummel, Werner,Mueller, Michael
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p. 4562 - 4571
(2007/10/03)
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- Asymmetric synthesis of S-(+)-argentilactone and S-(-)-goniothalamin
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The asymmetric synthesis of an α,β-unsaturated δ-lactone equivalent 8 as a key intermediate towards the total synthesis of a variety of natural products bearing such structural motifs is reported. An enzymatic approach was applied to provide both enantiomers of compound 8 using recLBADH (ee > 99%) and baker's yeast (ee = 94%), respectively. The utility of the intermediate was demonstrated by the total synthesis of the non-natural enantiomers of argentilactone [(S)-1] and goniothalamin [(S)-2].
- Job,Wolberg,Müller,Enders
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p. 1796 - 1798
(2007/10/03)
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- Highly regio- and enantioselective reduction of 3,5-dioxocarboxylates
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Only the keto group in position C-5 is reduced in the enzymatic reduction of 3,5-dioxocarboxylates by the alcohol dehydrogenase of Lactobacillusbrevis (LBADH; see scheme). The strategy of nature for manipulating β-keto metabolites inspired the development of a chemoenzymatic approach to virtually enantiopure 3,5-dihydroxycarboxylate building blocks. The crucial enzymatic step can be performed on an attractively large scale.
- Wolberg, Michael,Hummel, Werner,Wandrey, Christian,Mueller, Michael
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p. 4306 - 4308
(2007/10/03)
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- Lipase-catalyzed asymmetric synthesis of 6-(3-chloro-2-hydroxypropyl)-1,3-dioxin-4-ones and their conversion to chiral 5,6-epoxyhexanoates
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Highly enantioselective syntheses of (R)- and (S)-6-(3-chloro-2-hydroxypropyl)-1,3-dioxin-4-ones by means of lipase-catalyzed kinetic resolutions are described. Chiral dioxinones thus obtained have been converted to optically active 5,6-epoxyhexanoates, which are important precursors for a series of biologically active compounds.
- Sakaki,Sakoda,Sugita,Sato,Kaneko
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p. 343 - 346
(2007/10/02)
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