- One-Pot Enzymatic Synthesis of Cyclic Vicinal Diols from Aliphatic Dialdehydes via Intramolecular C?C Bond Formation and Carbonyl Reduction Using Pyruvate Decarboxylases and Alcohol Dehydrogenases
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An enzymatic cascade reaction was developed for one-pot enantioselective conversion of aliphatic dialdehydes to chiral vicinal diols using pyruvate decarboxylases (PDCs) and alcohol dehydrogenases (ADHs). The PDCs showed promiscuity in catalysing the cyclization of aliphatic dialdehydes through intramolecular stereoselective carbon-carbon bond formation. Consequently, 1,2-cyclopentanediols in three different stereoisomeric forms and 1,2-cyclohexanediols in two different stereoisomeric forms could be prepared with high conversion and stereoisomeric ratio from the respective initial substrates, glutaraldehyde and adipaldehyde. These cascade reactions represent a promising approach to the biocatalytic synthesis of important chiral vicinal diols. (Figure presented.).
- Zhang, Yan,Yao, Peiyuan,Cui, Yunfeng,Wu, Qiaqing,Zhu, Dunming
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- Site-Selective and Product Chemoselective Aliphatic C-H Bond Hydroxylation of Polyhydroxylated Substrates
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Site-selective and product chemoselective aliphatic C-H bond oxidation of 1,2-diols and of polyhydroxylated substrates using iron and manganese catalysts and hydrogen peroxide as terminal oxidant is described. The reaction capitalizes on the use of fluorinated alcohol solvents such as 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), which exert a strong polarity reversal in the hydroxyl moieties of 1,2-diols via hydrogen bonding, in turn translating into a strong deactivation of proximal C-H bonds against a HAT initiated oxidation by the putative high-valent and electrophilic metal-oxo species. As a result, site-selective and product chemoselective oxidation of complex polyfunctional molecules such as steroids, sugars, and pharmaceuticals is described, where exclusive or predominant C-H bond hydroxylation at a remote and nonactivated site takes place. The current report discloses HAT initiated hydroxylations in fluorinated alcohol solvents as methods displaying orthogonal chemoselectivity to contemporary alcohol oxidations providing a useful tool for synthetic planning in densely functionalized molecules.
- Bietti, Massimo,Borrell, Margarida,Costas, Miquel,Gil-Caballero, Sergio
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p. 4702 - 4709
(2020/05/19)
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- Enantioselective Cascade Biocatalysis via Epoxide Hydrolysis and Alcohol Oxidation: One-Pot Synthesis of (R)-α-Hydroxy Ketones from Meso- or Racemic Epoxides
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A new type of cascade biocatalysis was developed for one-pot enantioselective conversion of a meso- or racemic epoxide to an α-hydroxy ketone in high ee via an epoxide hydrolase-catalyzed hydrolysis of the epoxide, an alcohol dehydrogenase-catalyzed oxidation of the diol intermediate, and an enzyme-catalyzed cofactor regeneration. In vitro cascade biotransformation of meso-epoxides (cyclopentene oxide 1a, cyclohexene oxide 1b, and cycloheptene oxide 1c) was achieved with cell-free extracts containing recombinant SpEH (epoxide hydrolase from Sphingomonas sp. HXN-200), BDHA (butanediol dehydrogenase from Bacillus subtilis BGSC1A1), and LDH (lactate dehydrogenase form Bacillus subtilis) or NOX (NADH oxidase from Lactobacillus brevis DSM 20054), respectively, giving the corresponding (R)-α-hydroxycyclopentanone 3a, (R)-α-hydroxycyclohexanone 3b, and (R)-α-hydroxycycloheptanone 3c in 98-99% ee and 70-50% conversion with TTN of NAD+-recycling of 5500-26000. Cascade catalysis with mixed cells of Escherichia coli (SpEH) and E. coli (BDHA-NOX) converted 100-300 mM meso-epoxides 1a-1c to (R)-α-hydroxy ketones 3a-3c in 98-99% ee and 85-57% conversion. Cells of E. coli (SpEH-BDHA-NOX) coexpressing all three enzymes were also proven as good catalysts for the cascade conversion of 100-200 mM meso-epoxides 1a-1c, giving (R)-α-hydroxy ketones 3a-3c in 98-99% ee and 79-52% conversion. The cascade biocatalysis for one-pot synthesis of α-hydroxy ketone in high ee was also successfully demonstrated with a racemic epoxide (1,2,3,4-tetrahydronaphthalene-1,2-oxide 1d) as the substrate. By using two whole-cells based approaches, (R)-α-hydroxytetralone 3d was obtained in 99% ee and 49-40% conversion from 20 to 5 mM racemic epoxide 1d. Preparative cascade biotransformation of cyclohexene oxide 1b gave (R)-α-hydroxycyclohexanone 3b in 98% ee with 70% isolated yield. The developed new type of cascade biocatalysis is enantioselective, green, and often high yielding. The concept might be generally applicable to produce other useful enantiopure α-hydroxy ketones from the corresponding meso- or racemic epoxides by cascade catalysis using appropriate enzymes. (Chemical Equation Presented).
- Zhang, Jiandong,Wu, Shuke,Wu, Jinchuan,Li, Zhi
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- Enantioselective biooxidation of racemic trans-cyclic vicinal diols: One-pot synthesis of both enantiopure (S,S)-cyclic vicinal diols and (R)-α-hydroxy ketones
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Highly regio- and enantioselective alcohol dehydrogenases BDHA (2,3-butanediol dehydrogenase from Bacillus subtilis BGSC1A1), CDDHPm (cyclic diol dehydrogenase from Pseudomonas medocina TA5), and CDDHRh (cyclic diol dehydrogenase from Rhodococcus sp. Moj-3449) were discovered for the oxidation of racemic trans-cyclic vicinal diols. Recombinant Escherichia coli expressing BDHA was engineered as an efficient whole-cell biocatalyst for the oxidation of (±)-1,2-cyclopentanediol, 1,2-cyclohexanediol, 1,2-cycloheptane-diol, and 1,2-cyclooctanediol, respectively, to give the corresponding (R)-α-hydroxy ketones in >99% ee and (S,S)-cyclic diols in >99% ee at 50% conversion in one pot. Escherichia coli (BDHA-LDH) co-expressing lactate dehydrogenase (LDH) for intracellular regeneration of NAD+ catalyzed the regio- and enantioselective oxidation of (±)-1,2-dihydroxy-1,2,3,4- tetrahydronaphthalene to produce the corresponding (R)-α-hydroxy ketone in >99% ee and (S,S)-cyclic diol in 96% ee at 49% conversion. Preparative biotransformations were also demonstrated. Thus, a novel and useful method for the one-pot synthesis of both vicinal diols and α-hydroxy ketones in high ee was developed via high Copyright
- Zhang, Jiandong,Xu, Tingting,Li, Zhi
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supporting information
p. 3147 - 3153
(2013/12/04)
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- Chemoenzymatic synthesis of α′- And α-acetoxylated cyclic ketones
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α,β-Unsaturated and saturated cyclic ketones were selectively oxidized at the α′- and α-positions using Mn(OAc)3 and Pb(OAc)4, respectively, resulting in high chemical yields. The resultant racemic α′- and α-acetoxylated substrates were resolved into corresponding enantiomerically enriched α′- and α-hydroxylated and acetoxylated compounds with 96-98% ee via PLE hydrolysis. The absolute configurations of α′-acetoxy-α,β-unsaturated cyclic ketones were determined by transforming them into the corresponding saturated α-acetoxy cyclic ketones of known absolute configuration.
- Tanyeli, Cihangir,Turkut, Engin,Akhmedov, Idris Mecidoglu
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p. 1729 - 1733
(2007/10/03)
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- Enantioselective enzymatic approach to (+)- and (-)-2-acetoxy/hydroxycyclopentanones
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A new practical enzymatic approach to (+)- and (-)-2-acetoxy/hydroxycyclopentanones with 96-98% ee has been described via enzymatic hydrolysis of the meso-diacetate 2, Swern oxidation of the thus formed (±)-hydroxy acetates 3 and 4, followed by re-enzymatic resolution. Enantiomerically pure (+)- and (-)-2-hydroxycyclopentanones are in equilibrium with enediol 9 and slowly undergo racemisation, a process which could be arrested by protecting the hydroxyl group as the acetate.
- Easwar, Srinivasan,Desai, Shrivallabh B.,Argade, Narshinha P.,Ganesh, Krishna N.
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p. 1367 - 1371
(2007/10/03)
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- Preparation of Optically Active 1,2-Diols and α-Hydroxy Ketones Using Glycerol Dehydrogenase as Catalyst: Limits to Enzyme-Catalyzed Synthesis due to Noncompetitive and Mixed Inhibition by Product
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Glycerol dehydrogenase (GDH, EC 1.1.1.6, from Enterobacter aerogenes or Cellulomonas sp.) catalyzes the interconversion of analogues of glycerol and dihydroxyacetone.Its substrate specificity is quite different from than of horse liver alcohol dehydrogenase (HLADH), yeast alcohol dehydrogenase, and other alcohol dehydrogenases used in enzyme-catalyzed organic synthesis and is thus a useful new enzymic catalyst for the synthesis of enantiomerically enriched and isotopically labeled organic molecules.This paper illustrates synthetic applications of GDH as a reduction catalyst by the enantioselective reduction of 1-hydroxy-2-propanone and 1-hydroxy-2-butanone to the corresponding R 1,2-diols (ee = 95-98percent). (R)-1,2-Butanediol-2-d1 was prepared by using formate-d1 as the ultimate reducing agent.Comparison of (R)-1,2-butanediol prepared by reduction of 1-hydroxy-2-butanone enzymatically and with actively fermenting bakers' yeast indicated than yield and enantiomeric purity were similar by the two procedures.Reactions proceeding in the direction of substrate oxidation usually suffer from slow rates and incomplete conversions due to product inhibition.The kinetic consequences of product inhibition (competitive, noncompetitive, and mixed) for practical synthetic applications of GDH, HLADH, and other oxidoreductases are analyzed.In general, product inhibition seems the most serious limitation to the use of these enzymes as oxidation catalysts in organic synthesis.
- Lee, Linda G.,Whitesides, George M.
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