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Compounds structurally related to 2-cyclohexen-1-one 1,4-di-O-benzyl-L-threitol ketal were prepared and subjected to the Simmons-Smith cyclopropanation.From these experiments a mechanistic model for diastereoselective cyclopropanation of common ring systems (five-, six-, and seven-membered) has been formulated.Diastereoselectivity is thought to result from preferential chelation of the Simmons-Smith reagent at the least sterically hindered lone pair of electrons on the dioxolane oxygen proximal to the alkene.It is found that the presence of oxygen atoms in the dioxolane appendages provide sites for competitive chelation of the reagent, which can antagonize the diastereoselection due to chelation at dioxolane oxygen.That chelation by dioxolane oxygen does occur and is responsible for diastereoselectivity is inferred from studies with a hydrocarbon model system.Surprisingly, both dioxolane appendages are shown to be necessary for optimum diastereoselection since, under the conditions of the Simmons-Smith cyclopropanation, 2-cycloalken-1-one ethylene ketals are reversibly ring opened to zwitterionic intermediates.

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Reference:
Synthesis and Crystal Structure of a Chiral C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis,
Chiral lanthanide(III) complexes of sulphur–nitrogen–oxygen ligand derived from aminothiourea and sodium D-camphor-β-sulfonate

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The C2 amidine derivative (S,S)-1, as a twisted chiral dual acceptor for hydrogen bonding, was designed and synthesized. Enantioselective binding between (S,S)-1 and a series of diol enantiomers was investigated by NMR spectroscopy. High enantioselection above 1.0 kcal/mol was achieved in CDCl3. The association mode based on dual N···HO interactions was confirmed by intermolecular NOEs.

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Reference:
Synthesis and Crystal Structure of a Chiral C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis,
Chiral lanthanide(III) complexes of sulphur–nitrogen–oxygen ligand derived from aminothiourea and sodium D-camphor-β-sulfonate

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The alpha-hydroxy ketones are used as building blocks for compounds of pharmaceutical interest (such as antidepressants, HIV-protease inhibitors and antitumorals). They can be obtained by the action of enzymes or whole cells on selected substrates, such as diketones. We have studied the enantiospecificities of several fungal (AKR3C1, AKR5F and AKR5G) and human (AKR1B1 and AKR1B10) aldo-keto reductases in the production of alpha-hydroxy ketones and diols from vicinal diketones. The reactions have been carried out with pure enzymes and with an NADPH-regenerating system consisting of glucose-6-phosphate and glucose-6-phosphate dehydrogenase. To ascertain the regio and stereoselectivity of the reduction reactions catalyzed by the AKRs, we have separated and characterized the reaction products by means of a gas chromatograph equipped with a chiral column and coupled to a mass spectrometer as a detector. According to the regioselectivity and stereoselectivity, the AKRs studied can be divided in two groups: one of them showed preference for the reduction of the proximal keto group, resulting in the S-enantiomer of the corresponding alpha-hydroxy ketones. The other group favored the reduction of the distal keto group and yielded the corresponding R-enantiomer. Three of the AKRs used (AKR1B1, AKR1B10 and AKR3C1) could produce 2,3-butanediol from acetoin. We have explored the structure/function relationships in the reactivity between several yeast and human AKRs and various diketones and acetoin. In addition, we have demonstrated the utility of these AKRs in the synthesis of selected alpha-hydroxy ketones and diols.

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Reference:
Synthesis and Crystal Structure of a Chiral C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis,
Chiral lanthanide(III) complexes of sulphur–nitrogen–oxygen ligand derived from aminothiourea and sodium D-camphor-β-sulfonate

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Chiral induction has been achieved during a biomimetic cyclization of a chiral perillene derivatives in maximum 76percent diastereomeric excess.The absolute configuration of the predominant products are established by X-ray diffraction study and chemical transformations.

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Reference:
Synthesis and Crystal Structure of a Chiral C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis,
Chiral lanthanide(III) complexes of sulphur–nitrogen–oxygen ligand derived from aminothiourea and sodium D-camphor-β-sulfonate

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6-Isopropenyl 3-methyl 9-decene yl acetate (3S, 6R) has been synthesized from readily available trans(-)-dihydrocarvone.Regioselective ozonolysis of this ketone silyl enol ether is the key step of the sequence and allows to preserve both chiral centers.

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Reference:
Synthesis and Crystal Structure of a Chiral C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis,
Chiral lanthanide(III) complexes of sulphur–nitrogen–oxygen ligand derived from aminothiourea and sodium D-camphor-β-sulfonate

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Production of highly pure (2S,3S)-2,3-butanediol ((2S,3S)-2,3-BD) and (3S)-acetoin ((3S)-AC) in high concentrations is desirable but difficult to achieve. In the present study, glucose was first transformed to a mixture of (2S,3S)-2,3-BD and meso-2,3-BD by resting cells of Klebsiella pneumoniae CICC 10011, followed by biocatalytic resolution of the mixture by resting cells of Bacillus subtilis 168. meso-2,3-BD was transformed to (3S)-AC, leaving (2S,3S)-2,3-BD in the reaction medium. Using this approach, 12.5gl-1 (2S,3S)-2,3-BD and 56.7gl-1 (3S)-AC were produced. Stereoisomeric purity of (2S,3S)-2,3-BD and enantiomeric excess of (3S)-AC was 96.9 and 96.2%, respectively.

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Reference:
Synthesis and Crystal Structure of a Chiral C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis,
Chiral lanthanide(III) complexes of sulphur–nitrogen–oxygen ligand derived from aminothiourea and sodium D-camphor-β-sulfonate

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Asymmetric synthesis of (R,R)- and (S,S)-1,8,9,16- tetrahydroxytetraphenylenes was achieved from starting material (2R,3R)-butane-2,3-diol and (2S,3S)-butane-2,3-diol respectively by utilizing a center-to-axis strategy. A series of crown ether compounds 20, 24, and 25 and their corresponding enantiomers derived from chiral tetrahydroxytetraphenylene were synthesized in enantiomerically pure forms. Enantiomeric recognition properties of these hosts toward l- and d-amino acid methyl ester hydrochloride were studied by the UV spectroscopy titration. The tetramer hosts (S,S,S,S,S,S,S,S)-20 and (R,R,R,R,R,R,R,R)-20 exhibited the best enantioselectivities toward l- and d-alanine methyl ester hydrochloride salt with KL/KD = 4.1 and KD/KL = 3.9, respectively. The new chiral macrocyclic hosts would further enrich the host-guest chemistry.

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Reference:
Synthesis and Crystal Structure of a Chiral C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis,
Chiral lanthanide(III) complexes of sulphur–nitrogen–oxygen ligand derived from aminothiourea and sodium D-camphor-β-sulfonate

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Limonene epoxide hydrolase from Rhodococcus erythropolis DCL 14 (LEH) is known to be an exceptional epoxide hydrolase (EH) because it has an unusual secondary structure and catalyzes the hydrolysis of epoxides by a rare one-step mechanism in contrast to the usual two-step sequence. From a synthetic organic viewpoint it is unfortunate that LEH shows acceptable stereoselectivity essentially only in the hydrolysis of the natural substrate limonene epoxide, which means that this EH cannot be exploited as a catalyst in asymmetric transformations of other substrates. In the present study, directed evolution using iterative saturation mutagenesis (ISM) has been tested as a means to engineer LEH mutants showing broad substrate scope with high stereoselectivity. By grouping individual residues aligning the binding pocket correctly into randomization sites and performing saturation mutagenesis iteratively using a reduced amino acid alphabet, mutants were obtained which catalyze the desymmetrization of cyclopentene-oxide with stereoselective formation of either the (R,R)- or the (S,S)-diol on an optional basis. The mutants prove to be excellent catalysts for the desymmetrization of other meso-epoxides and for the hydrolytic kinetic resolution of racemic substrates, without performing new mutagenesis experiments. Since less than 5000 tranformants had to be screened for achieving these results, this study contributes to the generalization of ISM as a fast and reliable method for protein engineering. In order to explain some of the stereoselective consequences of the observed mutations, a simple model based on molecular dynamics simulations has been proposed.

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Reference:
Synthesis and Crystal Structure of a Chiral C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis,
Chiral lanthanide(III) complexes of sulphur–nitrogen–oxygen ligand derived from aminothiourea and sodium D-camphor-β-sulfonate

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The invention relates to the synthesis of boronic ester and acid compounds. More particularly, the invention provides improved synthetic processes for the large-scale production of boronic ester and acid compounds, including the peptide boronic acid proteasome inhibitor bortezomib.

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Reference:
Synthesis and Crystal Structure of a Chiral C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis,
Chiral lanthanide(III) complexes of sulphur–nitrogen–oxygen ligand derived from aminothiourea and sodium D-camphor-β-sulfonate

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A chimeric (2S, 3S)-butanediol dehydrogenase (cLBDH) was engineered to have the strict (S)-configuration specificity of the (2S, 3S)-BDH (BsLBDH) derived from Brevibacterium saccharolyticum as well as the enzymatic stability of the (2R, 3S)-BDH (KpMBDH) from Klebsiella pneumonia by swapping the domains of two native BDHs. However, while cLBDH possesses the stability, it lacks the specificity. In order to assist in the design a BDH having strict substrate specificity, an X-ray structural analysis of a cLBDH crystal was conducted at 1.58 A. The results obtained show some readily apparent differences around the active sites of cLBDH and BsLBDH. Based on this structural information, a novel (2S, 3S)-BDH having a preferred specificity was developed by introducing a V254L mutation into cLBDH. The influence of this mutation on the stability of cLBDH was not evaluated. Nevertheless, the technique described herein is an effective method for the production of a tailor-made BDH.

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Reference:
Synthesis and Crystal Structure of a Chiral C3-Symmetric Oxygen Tripodal Ligand and Its Applications to Asymmetric Catalysis,
Chiral lanthanide(III) complexes of sulphur–nitrogen–oxygen ligand derived from aminothiourea and sodium D-camphor-β-sulfonate