- The stereoselective preparation of β-hydroxy esters using a yeast reduction in an organic solvent
-
A range of (S)-β-hydroxy esters has been prepared in high yield (56-96%) and with very high enantioselectivity (>94%) using a yeast mediated reduction in light petroleum. It was found that the ester functionality had a marked effect on both the isolated yield and the quantity of yeast required to effect complete reduction.
- Medson, Caroline,Smallridge, Andrew J.,Trewhella, Maurie A.
-
-
Read Online
- Identification of a Robust Carbonyl Reductase for Diastereoselectively Building syn-3,5-Dihydroxy Hexanoate: A Bulky Side Chain of Atorvastatin
-
t-Butyl-6-cyano-(3R,5R)-dihydroxyhexanoate is an advanced chiral precursor for the synthesis of the side chain pharmacophore of cholesterol-lowering drug atorvastatin. Herein, a robust carbonyl reductase (LbCR) was newly identified from Lactobacillus brevis, which displays high activity and excellent diastereoselectivity toward bulky t-butyl 6-cyano-(5R)-hydroxy-3-oxo-hexanoate (7). The engineered Escherichia coli cells harboring LbCR and glucose dehydrogenase (for cofactor regeneration) were employed as biocatalysts for the asymmetric reduction of substrate 7. As a result, as much as 300 g L-1 of water-insoluble substrate was completely converted to the corresponding chiral diol with >99.5% de in a space-time yield of 351 g L-1 d-1, indicating a great potential of LbCR for practical synthesis of the very bulky and bi-chiral 3,5-dihydroxy carboxylate side chain of best-selling statin drugs.
- Gong, Xu-Min,Zheng, Gao-Wei,Liu, You-Yan,Xu, Jian-He
-
supporting information
p. 1349 - 1354
(2017/09/23)
-
- Enhanced enantioselectivity in the heterogeneous catalytic hydrogenation of acetoacetate esters into the corresponding 3-hydroxybutyrates using commercial nickel powder
-
Heterogeneous catalytic hydrogenation of acetoacetic acid esters over tartaric acid/NaBr-modified Ni powder was determined to be a critical function of the steric bulk of the ester moiety to afford quantitatively 3-hydroxybutyrate in 94% enantiomeric excess when ethyl and i-butyl esters are used, providing a facile route to optically active 3-hydroxybutyrates.
- Osawa, Tsutomu,Kizawa, Tomoko,Ikeda, Shinji,Kitamura, Takayuki,Inoue, Yoshihisa,Borovkov, Victor
-
p. 1630 - 1633
(2015/01/09)
-
- Asymmetric β-boration of α,β-unsaturated carbonyl compounds with chiral Rh[bis(oxazolinyl)phenyl] catalysts
-
Chiral rhodium[bis(oxazolinyl)phenyl] complexes exhibited high catalytic activity for the β-boration of α,β-unsaturated esters, ketones, and amides with bis(pinacolato)diboron in the presence of sodium tert-butoxide to attain high enantioselectivity of up to 97%. The substrate scope and catalytic mechanism were discussed.
- Toribatake, Kenji,Zhou, Li,Tsuruta, Ayae,Nishiyama, Hisao
-
p. 3551 - 3560
(2013/05/08)
-
- Highly enantioselective bioreduction of prochiral ketones by stem and germinated plant of Brassica oleracea variety italica
-
An eco-friendly and environmentally benign asymmetric reduction of a broad range of prochiral ketones employing Brassica oleracea variety italica (stems and germinated plant) as a novel biocatalyst was developed. It was found that B. oleracea variety italica could be used effectively for enantioselective bioreduction in aqueous medium with moderate to excellent chemical yield and enantiomeric excess (ee). This process is more efficient and generates less waste than conventional chemical reagents or microorganisms. Both R- and S-configurations were obtained by these asymmetric reactions. The best ee were achieved for pyridine derivatives (92-99%). The ee in germinated plant reactions were significantly higher than those of stem reactions. The low cost and the easy availability of these biocatalysts suggest their possible use for large scale preparations of important chiral alcohols.
- Mohammadi, Mehdi,Yousefi, Maryam,Habibi, Zohreh
-
experimental part
p. 328 - 336
(2012/03/11)
-
- Switching from S- to R-selectivity in the Candida antarctica lipase B-catalyzed ring-opening of ω-methylated lactones: Tuning polymerizations by ring size
-
Novozym 435-catalyzed ring-opening of a range of ω-methylated lactones demonstrates fascinating differences in rate of reaction and enantioselectivity. A switch from S- to R-selectivity was observed upon going from small (ring sizes ≤7) to large lactones (ring sizes ≥8). This was attributed to the transition from a cisoid to a transoid conformational preference of the ester bond on going from small to large lactones. The S-selectivity of the ring-opening of the small, cisoid lactones was low to moderate, while the R-selectivity of the ring-opening of the large transoid lactones was surprisingly high. The S-selectivity of the ring-opening of the small, cisoid lactones combined with the established R-selectivity of the transesterification of (aliphatic) secondary alcohols prevented polymerization from taking place. Ring-opening of the large, transoid lactones was R-selective with high enantioselectivity. As a result, these lactones could be polymerized, without exception, by straightforward kinetic resolution polymerization, yielding the enantiopure R-polyester with excellent enantiomeric excess (>99%).
- Van Buijtenen, Jeroen,Van As, Bart A. C.,Verbruggen, Marloes,Roumen, Luc,Vekemans, Jef A. J. M.,Pieterse, Koen,Hilbers, Peter A. J.,Hulshof, Lumbertus A.,Palmans, Anja R. A.,Meijer
-
p. 7393 - 7398
(2008/02/08)
-
- A new class of versatile chiral-bridged atropisomeric diphosphine ligands: Remarkably efficient ligand syntheses and their applications in highly enantioselective hydrogenation reactions
-
A series of chiral diphosphine ligands denoted as PQ-Phos was prepared by atropdiastereoselective Ullmann coupling and ring-closure reactions. The Ullmann coupling reaction of the biaryl diphosphine dioxides is featured by highly efficient central-to-axial chirality transfer with diastereomeric excess >99%. This substrate-directed diastereomeric biaryl coupling reaction is unprecedented for the preparation of chiral diphosphine dioxides, and our method precludes the tedious resolution procedures usually required for preparing enantiomerically pure diphosphine ligands. The effect of chiral recognition was also revealed in a relevant asymmetric ring-closure reaction. The chiral tether bridging the two aryl units creates a conformationally rigid scaffold essential for enantiofacial differentiation; fine-tuning of the ligand scaffold (e.g., dihedral angles) can be achieved by varying the chain length of the chiral tether. The enantiomerically pure Ru- and Ir-PQ-Phos complexes have been prepared and applied to the catalytic enantioselective hydrogenations of α- and β-ketoesters (C=O bond reduction), 2-(6′-methoxy- 2′-naphthyl)-propenoic acid, alkyl-substituted β-dehydroamino acids (C=C bond reduction), and N-heteroaromatic compounds (C=N bond reduction). An excellent level of enantioselection (up to 99.9% ee) has been attained for the catalytic reactions. In addition, the significant ligand dihedral angle effects on the Ir-catalyzed asymmetric hydrogenation of N-heteroaromatic compounds were also revealed.
- Qiu, Liqin,Kwong, Fuk Yee,Wu, Jing,Lam, Wai Har,Chan, Shusun,Yu, Wing-Yiu,Li, Yue-Ming,Guo, Rongwei,Zhou, Zhongyuan,Chan, Albert S. C.
-
p. 5955 - 5965
(2007/10/03)
-
- METHOD OF PREPARATION OF OPTICALLY ACTIVE ALCOHOLS
-
The present invention relates to a method for preparing chiral alcohol having optical activity. More specifically, the present invention relates to a method for preparing (S)-chiral alcohol with a high yield and a high optical purity by mixing achiral substrates such as racemic alcohol or ketone with metal catalyst and protein hydrolase to perform a dynamic kinetic resolution reaction.
- -
-
Page/Page column 19
(2010/02/10)
-
- Synthesis of Novel Diastereomeric Diphosphine Ligands and Their Applications in Asymmetric Hydrogenation Reactions
-
(Matrix Presented) Diastereomeric biaryl diphosphine ligands 10 and 11 with added chiral centers on the backbone were synthesized. Substrate-directed asymmetric synthesis occurred in the coupling step of the preparation of the diastereomeric diphosphine oxides. The diastereomeric diphosphine oxides were easily separated by column chromatography with silica gel. Ruthenium catalysts containing these ligands were highly effective in the hydrogenation of 2-(6′-methoxy-2′-naphthyl)propenoic acid and β-ketoesters. The additional chiral centers had a significant influence on the enantioselectivity and activity of the catalysts.
- Qiu, Liqin,Qi, Jianying,Pai, Cheng-Chao,Chan, Shusun,Zhou, Zhongyuan,Choi, Michael C. K.,Chan, Albert S. C.
-
p. 4599 - 4602
(2007/10/03)
-
- Synthesis of new chiral diphosphine ligand (BisbenzodioxanPhos) and its application in asymmetric catalytic hydrogenation
-
The new chiral diphosphine ligand [(5,6), (5′,6′)-bis(1,2-ethylenedioxy)biphenyl-2,2′-diyl]bis (diphenylphosphine) (BisbenzodioxanPhos) has been successfully prepared and used in ruthenium-catalyzed asymmetric hydrogenation of 2-(6′-methoxy-2′-naphthyl)propenoic acid and β-keto esters with high enantioselectivity (92.2% and up to 99.5% ee, respectively).
- Pai, Cheng-Chao,Li, Yue-Ming,Zhou, Zhong-Yuan,Chan, Albert S.C
-
p. 2789 - 2792
(2007/10/03)
-
- Synthesis and structural characterization of a highly effective chiral dipyridylphosphine ligand and its application in the Ru-catalyzed asymmetric hydrogenation of β-ketoesters
-
A new chiral dipyridylphosphine ligand Tol-P-Phos has been synthesized and the structure of the complex of (R)-Tol-P-Phos oxide with (-)-dibenzoyl-L-tartaric acid [(-)-DBT] was determined by single crystal X-ray diffraction. The ruthenium complex of Tol-P-Phos, Ru(R-Tol-P-Phos)(C6H6)Cl2, has been found to be a highly active and enantioselective catalyst in the asymmetric hydrogenation of β-ketoesters (up to 98.2% e.e.). The catalyst is also found to be air-stable even in solution.
- Wu,Chen,Zhou,Yeung,Chan
-
p. 1050 - 1054
(2007/10/03)
-
- Biocatalysis in Ionic Liquids: Markedly Enhanced Enantioselectivity of Lipase
-
matrix presented Lipase-catalyzed transesterifications in ionic liquids proceeded with markedly enhanced enantioselectivity. It was observed that lipases were up to 25 times more enantioselective in ionic liquids than in conventional organic solvents.
- Kim, Kwang-Wook,Song, Boyoung,Choi, Min-Young,Kim, Mahn-Joo
-
p. 1507 - 1509
(2007/10/03)
-
- Lipase promoted asymmetric trans-esterification of 4-alkyl-, 3-alkyl- and 3,4-dialkyloxetan-2-ones with ring-opening
-
Kinetic resolution of(+/-)-4-substituted [(+/-)-1], 3-substituted [(+/-)-4] and 3,4-disubstituted oxetan-2-ones [(+/-)-7] was effected by the action of lipases in organic solvents. The substrates (+/-)-1, (+/-)-4 and (+/-)-7 were prepared by [2 + 2] cycloaddition of aldehydes with ketene, intramolecular substitution of 3-bromoalkanoic acids and the Adam's cyclization of anti- and syn-3-hydroxyalkanoic acids, respectively. Lipase PS exhibited good activity towards all the oxetanones and was employed for the resolution experiments except with (+/-)-4-methyloxetan-2-one (+/-)-1a for which PPL was used. The stereoselectivity was satisfactory for obtaining oxetan-2-ones of high ee's except for a few cases. The configuration of new compounds was established by chemical correlation and CD spectroscopy.
- Sakai, Naoko,Ageishi, Satoru,Isobe, Hiroshi,Hayashi, Yoshiyuki,Yamamoto, Yukio
-
-
- 170. Probing the helical secondary structure of short-chain β-peptides
-
Structural prerequisites for the stability of the 31 helix of β-peptides can be defined from inspection of models (Figs. 1 and 2): lateral non-H-substituents in 2- and 3-position on the 3-amino-acid residues of the helix are allowed, axial ones are forbidden. To be able to test this prediction, we synthesized a series of heptapeptide derivatives Boc-(β-HVal-β-HAla-β-HLeu-Xaa-β-HVal-β-HAla-β- HLeu)-OMe 13-22 (Xaa = α- or β-amino-acid residue) and a β-depsipeptide 25 with a central (S)-3-hydroxybutanoic-acid residue (Xaa = -OCH(Me)CH2C(O)-) (Schemes 1-3). Detailed NMR analysis (DQF-COSY, HSQC, HMBC, ROESY, and TOCSY experiments) in methanol solution of the β-hexapeptide H(-β-HVal-β-HAla-β-HLeu)2-OH (1) and of the β-heptapeptide H-β-HVal-β-HAla-β-HLeu-(S,S)-β-HAla(α Me)-β-HVal-β-HAla-β-HLeu-OH (22), with a central (2S,3S)-3-amino-2-methylbutanoic-acid residue, confirm the helical structure of such β-peptides (previously discovered in pyridine solution) (Fig. 3 and Tables 1-5). The CD spectra of helical β-peptides, the residues of which were prepared by (retentive) Arndt-Eistert homologation of the (S)- or L-α-amino acids, show a trough at 215 nm. Thus, this characteristic pattern of the CD spectra was taken as an indicator for the presence of a helix in methanol solutions of compounds 13-22 and 25 (including partially and fully deprotected forms) (Figs. 4-6) The results fully confirm predicted structural effects: incorporation of a single 'wrong' residue ((R)-β-HAla,β-HAibs (R,S)-β-HAla(α Me), or N-Me-β-HAla) in the central position of the β-heptapeptide derivatives A (see 17, 18, 20, or 21, resp.) causes the CD minimum to disappear. Also, the β-heptadepsipetide 25 (missing H-bond) and the β-heptapeptide analogs with a single α-amino-acid moiety in the middle (13 and 14) are not helical, according to this analysis. An interesting case is the heptapeptide 15 with the central achiral, unsubstituted 3-aminopropanoicacid moiety: helical conformation appears to depend upon the presence or absence of terminal protection and upon the solvent (MeOH vs. MeOH/H2O).
- Seebach, Dieter,Ciceri, Paola E.,Overhand, Mark,Jaun, Bernhard,Rigo, Dario,Oberer, Lukas,Hommel, Ulrich,Amstutz, Rene,Widmer, Hans
-
p. 2043 - 2066
(2007/10/03)
-
- Lipase-promoted asymmetric transesterification of 4-alkyloxetan-2-ones with ring-opening
-
Lipase-catalysed reaction of (+/-)-4-alkyloxetan-2-ones 1a-c with benzyl alcohol gave (R)-1a (R=Me) (36percent, 96percent ee) and benzyl (S)-3-hydroxybutanoate 2a (51percent, 85percent ee), (R)-1b (R=Pr) (42percent, 75percent ee) and benzyl (S)-3-hydroxyhexanoate 2b (45percent, 69percent ee) and (S)-1c (R=Pr-i, 41percent, 95percent ee) and benzyl (R)-3-hydroxy-4-methylpentanoate 2c (43percent, 90percent ee), respectively.
- Koichi, Yota,Suginaka, Kaoru,Yamamoto, Yukio
-
p. 1645 - 1646
(2007/10/02)
-