6426-26-2Relevant articles and documents
Composition and structure of activated complexes in stereoselective deprotonation of cyclohexene oxide by a mixed dimer of chiral lithium amide and lithiated imidazole
Pettersen, Daniel,Diner, Peter,Amedjkouh, Mohamed,Ahlberg, Per
, p. 1607 - 1613 (2004)
Stereoselective deprotonation of cyclohexene oxide, using a mixed dimer built of the chiral lithium amide, lithium (1R,2S)-N-methyl-1-phenyl-2- pyrrolidinyl-propanamide, and 2-lithio-1-methylimidazole, has been studied. The composition of the rate limiting activated complex was determined by kinetics to be built from one mixed dimer molecule and one epoxide molecule. Based on this knowledge computational chemistry has been applied to gain insight into possible structures of the activated complexes.
Catalytic asymmetric chiral lithium amide-promoted epoxide rearrangement: A NMR spectroscopic and kinetic investigation
Diner, Peter
, p. 2733 - 2739 (2010)
The lithium amide derived from the chiral diamine (1R,3S,4S)-3-(1- pyrrolidinyl)methyl-2-azabicyclo[2.2.1]heptane, has been reported to catalytically deprotonate cyclohexene oxide and other epoxides, yielding chiral allylic alcohols in excellent enantiomeric excess. In this work, 6Li, 1H and 13C NMR spectroscopy have been used to study the aggregation of the chiral lithium amide in THF and the influence on the aggregation by the addition of additives, such as 1,8-diazabicyclo-[5.4.0]undec- 7-ene (DBU). The activated complex under catalytic deprotonation of cyclohexene oxide, that is, with excess Li-DBU and free DBU, is built from one monomer of the chiral lithium amide, one molecule of epoxide and one additional molecule of DBU. The reaction order (-0.97) obtained for the bulk base Li-DBU shows an inverse dependence on the concentration, suggesting a deaggregation of the initial mixed dimer to a monomer-based transition state containing a monomer of the lithium amide.
On the novel function of the additive DBU. Catalytic stereoselective deprotonation by a mixed dimer of lithiated DBU and a chiral lithium amide
Pettersen, Daniel,Amedjkouh, Mohamed,Nilsson Lill, Sten O.,Ahlberg, Per
, p. 1397 - 1405 (2002)
The additive DBU is used to increase the selectivity and reactivity of e.g. chiral lithium amides in both catalysed and non-catalysed asymmetric syntheses. This has been attributed to the coordinating ability of DBU favoring more reactive aggregates. However, we have found that LDA in THF deprotonates DBU to yield lithiated DBU (1) as shown by multinuclear NMR studies. Furthermore, compound 1 is found to form a mixed dimer (5) with e.g. the norephedrine-derived chiral lithium amide 2. Results of an investigation of the stereoselectivity of this novel reagent in the epoxide deprotonation are also reported. Computational studies using PM3 and DFT show possible structures of 1 and 5 in line with the NMR results. In addition, the role of THF and DBU in the solvation of the aggregates has been investigated by computational modelling and favoured complexes in the equilibria between homo- and heterocomplexes are also reported.
Improved enantioselectivity by using novel bulk bases in chiral lithium amide catalysed deprotonations: Mixed dimers as reagents and catalysts
Pettersen, Daniel,Amedjkouh, Mohamed,Ahlberg, Per
, p. 4669 - 4673 (2002)
Novel bulk bases have been developed yielding improved enantioselectivity of chiral lithium amide catalysed deprotonations as compared to using the bulk base lithium diisopropylamide (LDA). The new bulk bases are 2-lithio-1-methylimidazole, 2-(lithiomethyl)-1-methylimidazole, 2-lithio-furan and 1,8-diazabicyclo-6-lithio[5.4.0]undec-7-ene which have been used together with chiral lithium amides in deprotonations of cyclohexene oxide. Using the chiral lithium amides enhanced stereoselectivities (96% ee) have been reached. The reactivity change has been traced to the formation of novel reagents - mixed dimers - formed from a bulk base molecule and a molecule of a chiral lithium amide. The results also show that DBU, which has commonly been used as an additive to alter reactivity and enantioselectivity in deprotonations, has another important role. DBU is lithiated under the conditions used and becomes a bulk base, which forms catalytic mixed dimers with the chiral lithium amides.
CHOLINE METABOLISM INHIBITORS
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Page/Page column 50; 102-103, (2020/07/05)
The present disclosure relates to compounds, compositions and methods for inhibiting choline metabolism, e.g., conversion of choline to trimethylamine. Disclosed herein are compounds, compositions, and methods for inhibiting choline metabolism, e.g., conversion of choline to TMA. Also disclosed herein are compounds, methods and compositions for inhibiting choline metabolism by gut microbiota resulting in reduction in the formation of trimethylamine (TMA) and trimethylamine N-oxide (TMAO).
Synthesis of oxazolidinone from enantiomerically enriched allylic alcohols and determination of their molecular docking and biologic activities
Atmaca, Ufuk,Kaya, Rüya,Karaman, Halide Sedef,?elik, Murat,Gül?in, ?lhami
, (2019/06/08)
Enantioselective synthesis of functionalized cyclic allylic alcohols via kinetic resolution in transesterifcation with different lipase enzymes has been developed. The influence of the enzymes and temperature activity was studied. By determination of ideal reaction conditions, byproduct formation is minimized; this made it possible to prepare enantiomerically enriched allylic alcohols in high ee's and good yields. Enantiomerically enriched allylic alcohols were used for enantiomerically enriched oxazolidinone synthesis. Using benzoate as a leaving group means that 1 mol % of potassium osmate is necessary and can be obtained high yields 98%. Inhibitory activities of enantiomerically enriched oxazolidinones (8, 10 and 12) were tested against human carbonic anhydrase I and II isoenzymes (hCA I and hCA II), acetylcholinesterase (AChE), and α-glycosidase (α-Gly) enzymes. These enantiomerically enriched oxazolidinones derivatives had Ki values in the range of 11.6 ± 2.1–66.4 ± 22.7 nM for hCA I, 34.1 ± 6.7–45.2 ± 12.9 nM for hCA II, 16.5 ± 2.9 to 35.6 ± 13.9 for AChE, and 22.3 ± 6.0–70.9 ± 9.9 nM for α-glycosidase enzyme. Moreover, they had high binding affinity with ?5.767, ?6.568, ?9.014, and ?8.563 kcal/mol for hCA I, hCA II, AChE and α-glycosidase enzyme, respectively. These results strongly supported the promising nature of the enantiomerically enriched oxazolidinones as selective hCA, AChE, and α-glycosidase inhibitors. Overall, due to these derivatives’ inhibitory potential on the tested enzymes, they are promising drug candidates for the treatment of diseases like glaucoma, leukemia, epilepsy; Alzheimer's disease; type-2 diabetes mellitus that are associated with high enzymatic activity of CA, AChE, and α-glycosidase.
Enantioselective Hydrogenation of Ketones using Different Metal Complexes with a Chiral PNP Pincer Ligand
Garbe, Marcel,Wei, Zhihong,Tannert, Bianca,Spannenberg, Anke,Jiao, Haijun,Bachmann, Stephan,Scalone, Michelangelo,Junge, Kathrin,Beller, Matthias
supporting information, p. 1913 - 1920 (2019/03/13)
The synthesis of different metal pincer complexes coordinating to the chiral PNP ligand bis(2-((2R,5R)-2,5-dimethyl-phospholanoethyl))amine is described in detail. The characterized complexes with Mn, Fe, Re and Ru as metal centers showed good activities regarding the reduction of several prochiral ketones. Comparing these catalysts, the non-noble metal complexes produced best selectivities not only for aromatic substrates, but also for different kinds of aliphatic ones leading to enantioselectivities up to 99% ee. Theoretical investigations elucidated the mechanism and rationalized the selectivity. (Figure presented.).
CHIRAL METAL COMPLEX COMPOUNDS
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Page/Page column 18; 19; 22; 24; 28, (2018/11/10)
The invention comprises novel chiral metal complex compounds of the formula (I) wherein M, PR2, R3 and R4 are outlined in the description, its stereoisomers, in the form as a neutral complex or a complex cation with a suitable counter ion. The chiral metal complex compounds can be used in asymmetric reactions, particularly in asymmetric reductions of ketones, imines or oximes.
Manganese(I)-Catalyzed Enantioselective Hydrogenation of Ketones Using a Defined Chiral PNP Pincer Ligand
Garbe, Marcel,Junge, Kathrin,Walker, Svenja,Wei, Zhihong,Jiao, Haijun,Spannenberg, Anke,Bachmann, Stephan,Scalone, Michelangelo,Beller, Matthias
supporting information, p. 11237 - 11241 (2017/09/02)
A new chiral manganese PNP pincer complex is described. The asymmetric hydrogenation of several prochiral ketones with molecular hydrogen in the presence of this complex proceeds under mild conditions (30–40 °C, 4 h, 30 bar H2). Besides high catalytic activity for aromatic substrates, aliphatic ketones are hydrogenated with remarkable selectivity (e.r. up to 92:8). DFT calculations support an outer sphere hydrogenation mechanism as well as the experimentally determined stereochemistry.
Caution in the Use of Nonlinear Effects as a Mechanistic Tool for Catalytic Enantioconvergent Reactions: Intrinsic Negative Nonlinear Effects in the Absence of Higher-Order Species
Kalek, Marcin,Fu, Gregory C.
supporting information, p. 4225 - 4229 (2017/03/27)
Investigation of the dependence of product enantiometric excess (ee) on catalyst ee is a widely used tool to probe the mechanism of an enantioselective reaction; in particular, the observation of a nonlinear relationship is usually interpreted as an indication of the presence of one or more species that contain at least two units of the chiral entity. In this report, we demonstrate that catalytic enantioconvergent reactions can display an intrinsic negative nonlinear effect that originates purely from the kinetic characteristics of certain enantioconvergent processes and is independent of possible aggregation of the chiral entity. Specifically, this intrinsic negative nonlinear effect can arise when there is a kinetic resolution of the racemic starting material, and its magnitude is correlated with the selectivity factor and the conversion; the dependence on conversion provides a ready means to distinguish it from a more conventional nonlinear effect. We support our analysis with experimental data for two distinct enantioconvergent processes, one catalyzed by a chiral phosphine and the other by a chiral Pd/phosphine complex.
