Stereoselective synthesis of (R)-3-quinuclidinol through asymmetric reduction of 3-quinuclidinone with 3-quinuclidinone reductase of Rhodotorula rubra

Uzura, Atsuko; Nomoto, Fumiki; Sakoda, Akiko; Nishimoto, Yukifumi; Kataoka, Michihiko; Shimizu, Sakayu

doi:10.1007/s00253-009-1902-2

Cited by 37 publications

(25 citation statements)

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“…The group of red to pinkish yeasts is one of the most interesting biocatalysts [30][31][32][33] in the reduction of differently substituted arylketones and among them Sporobolomyces salmonicolor is the best known for this application. As expected, this yeast was able to produce the desired product 5a in a quantitative yield with 80% e.e.…”

Section: Resultsmentioning

confidence: 99%

Simple 1,3-diamines and their application as ligands in ruthenium(ii) catalysts for asymmetric transfer hydrogenation of aryl ketones

et al. 2015

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In this research work simple unsymmetrical 1,3-diamines were studied. The synthesis of the diamines started from non-commercial available compounds. S-5a and S,S-5c were obtained by biocatalysis with non conventional yeast, Rhodotorula rubra MIM 147, with excellent 99% e.e. and d.e. up to 90%. Different approaches of synthesis were applied to the same backbone to study both the steric and electronic effects of the ligands. The reactivity of the corresponding ruthenium complexes was evaluated in the asymmetric hydrogen transfer reduction of acetophenone as a standard substrate and of other different aryl ketones, highlighting the flexibility of the six membered chelating ring. A screening of the reaction conditions indicated aqueous media in the presence of HCOONa as a hydrogen donor to be the best system for overcoming the lack of stereocontrol thus allowing us to obtain 56% e.e. in the reduction of acetophenone with the complex in which the ligand was diamine 1, revealed as the best in terms of reactivity and stereoselectivity also in the reduction of the other different aryl ketones, in particular for a-tetralone, i (63% e.e.).

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Section: Resultsmentioning

confidence: 99%

Simple 1,3-diamines and their application as ligands in ruthenium(ii) catalysts for asymmetric transfer hydrogenation of aryl ketones

et al. 2015

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“…A protein blast search with the QNR enzyme showed the highest identity was 68.4%, with a putative SDR in Streptosporangium roseum. The identities with known 3-quinuclidinone-reducing enzymes were very low: 24.4% with NADPH-dependent 3-quinuclidinone reductase of R. rubra (mucilaginosa) (13), 27.4% with tropinone reductase I, and 29.8% with tropinone reductase II (12). Therefore, QNR is a novel enzyme belonging to the SDR family.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, BacC may also play a role in bacilysin biosynthesis, especially in the oxidoreduction of the bacilysin precursor, with reduction of the carbonyl or double bond of the compound, although the accurate reaction has not yet been clarified. Table 4 shows the enzymatic properties of QNR and BacC compared with a 3-quinuclidinone reductase from the yeast R. rubra (13). The K m values of QNR (6.5 mM) and BacC (13.8 mM) for 3-quinuclidinone in the reductive reaction were much lower than that of NADPH-dependent 3-quinuclidinone reductase from R. rubra (145 mM).…”

Section: Discussionmentioning

confidence: 99%

“…Yamamoto et al reported the production of (R)-(Ϫ)-3-quinuclidinol using recombinant formate dehydrogenase (FDH) and tropinone reductase (14). Uzura et al reported a reaction system using recombinant glucose dehydrogenase and 3-quinuclidinone reductase from Rhodotorula rubra (13). The optical resolution of (Ϯ)-3-quinuclidinol esters by the hydrolysis reaction of Aspergillus melleus protease was reported by Nomoto et al (15).…”

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confidence: 99%

“…It has been used as the chiral synthone for a cognition enhancer, a bronchodilator, and a urinary incontinence agent (11). The following enzymes have been reported to catalyze the reduction of 3-quinuclidinone to (R)-(Ϫ)-3-quinuclidinol: tropinone reductase, from the plant henbane (Solanaceae, Hyoscyamus niger) (12), and NADPH-dependent 3-quinuclidinone reductase (QNR), from the yeast Rhodotorula rubra (mucilaginosa) (13). Yamamoto et al reported the production of (R)-(Ϫ)-3-quinuclidinol using recombinant formate dehydrogenase (FDH) and tropinone reductase (14).…”

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confidence: 99%

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Gene Cloning and Characterization of Two NADH-Dependent 3-Quinuclidinone Reductases from Microbacterium luteolum JCM 9174

Isotani

Kurokawa

Suzuki

et al. 2013

Appl Environ Microbiol

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We used the resting-cell reaction to screen approximately 200 microorganisms for biocatalysts which reduce 3-quinuclidinone to optically pure (R)-(؊)-3-quinuclidinol. Microbacterium luteolum JCM 9174 was selected as the most suitable organism. The genes encoding the protein products that reduced 3-quinuclidinone were isolated from M. luteolum JCM 9174. The bacC gene, which consists of 768 nucleotides corresponding to 255 amino acid residues and is a constituent of the bacilysin synthetic gene cluster, was amplified by PCR based on homology to known genes. The qnr gene consisted of 759 nucleotides corresponding to 252 amino acid residues. Both enzymes belong to the short-chain alcohol dehydrogenase/reductase (SDR) family. The genes were expressed in Escherichia coli as proteins which were His tagged at the N terminus, and the recombinant enzymes were purified and characterized. Both enzymes showed narrow substrate specificity and high stereoselectivity for the reduction of 3-quinuclidinone to (R)-(؊)-3-quinuclidinol. Many methods have been used for the synthesis of optically pure isomers, including enantioselective synthesis, derivatization of natural compounds, and the optical resolution of racemic compounds. Enantioselective organic synthesis is the most efficient and attractive method for producing chiral starting materials for pharmaceuticals and agrochemicals. Chiral metal catalysts such as BINAP-Ru (1) and chiral Co(II) salen complex (2, 3) have been successfully used in producing chiral alcohols or chiral diols from various ketones or epoxides. However, these catalysts are costly and leave trace metal contamination in the products, and they are sometimes difficult to handle. The enzymatic reduction of ketones to optically pure alcohols is more environmentally sustainable and thus more attractive for pharmaceutical manufacturing (4). Several excellent methods using biocatalysts have been reported for producing chiral alcohols (5-10).(R)-(Ϫ)-3-Quinuclidinol, which has a double-ring structure containing nitrogen, is a valuable intermediate for pharmaceuticals. It has been used as the chiral synthone for a cognition enhancer, a bronchodilator, and a urinary incontinence agent (11). The following enzymes have been reported to catalyze the reduction of 3-quinuclidinone to (R)-(Ϫ)-3-quinuclidinol: tropinone reductase, from the plant henbane (Solanaceae, Hyoscyamus niger) (12), and NADPH-dependent 3-quinuclidinone reductase (QNR), from the yeast Rhodotorula rubra (mucilaginosa) (13). Yamamoto et al. reported the production of (R)-(Ϫ)-3-quinuclidinol using recombinant formate dehydrogenase (FDH) and tropinone reductase (14). Uzura et al. reported a reaction system using recombinant glucose dehydrogenase and 3-quinuclidinone reductase from Rhodotorula rubra (13). The optical resolution of (Ϯ)-3-quinuclidinol esters by the hydrolysis reaction of Aspergillus melleus protease was reported by Nomoto et al. (15).In this study, we report two novel 3-quinuclidinone reductase genes, qnr and bacC, from Microbacterium luteolu...

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et al. 2012

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Stereoselective synthesis of (R)-3-quinuclidinol through asymmetric reduction of 3-quinuclidinone with 3-quinuclidinone reductase of Rhodotorula rubra

Cited by 37 publications

References 25 publications

Simple 1,3-diamines and their application as ligands in ruthenium(ii) catalysts for asymmetric transfer hydrogenation of aryl ketones

Simple 1,3-diamines and their application as ligands in ruthenium(ii) catalysts for asymmetric transfer hydrogenation of aryl ketones

Gene Cloning and Characterization of Two NADH-Dependent 3-Quinuclidinone Reductases from Microbacterium luteolum JCM 9174

Reactions Involving Dehydrogenases

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