- Enantio- and Diastereodivergent Sequential Catalysis Featuring Two Transition-Metal-Catalyzed Asymmetric Reactions
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This study demonstrates the feasibility and inherent benefits of combining two distinct asymmetric transition-metal-catalyzed reactions in one pot. The reported transformation features a Pd-catalyzed asymmetric allylic alkylation and a Rh-catalyzed enantioselective 1,4-conjugate addition, effectively converting simple allyl enol carbonate precursors into enantioenriched cyclic ketones with two remote stereocenters. Despite the anticipated challenges associated with controlling stereoselectivity in such a complex system, the products are obtained in enantiomeric excesses ranging up to >99 % ee, exceeding those obtained from either of the individual asymmetric reactions. In addition, since the stereoselectivity of both steps is under catalyst control, this one-pot reaction is enantio- and diastereodivergent, enabling facile access to all stereoisomers from the same set of starting materials.
- Abel-Snape, Xavier,Lautens, Mark,Masson-Makdissi, Jeanne,Prieto, Liher
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supporting information
p. 16932 - 16936
(2021/07/02)
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- Copper(I) Phosphinooxazoline Complexes: Impact of the Ligand Substitution and Steric Demand on the Electrochemical and Photophysical Properties
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A series of seven homoleptic CuI complexes based on hetero-bidentate P^N ligands was synthesized and comprehensively characterized. In order to study structure–property relationships, the type, size, number and configuration of substituents at the phosphinooxazoline (phox) ligands were systematically varied. To this end, a combination of X-ray diffraction, NMR spectroscopy, steady-state absorption and emission spectroscopy, time-resolved emission spectroscopy, quenching experiments and cyclic voltammetry was used to assess the photophysical and electrochemical properties. Furthermore, time-dependent density functional theory calculations were applied to also analyze the excited state structures and characteristics. Surprisingly, a strong dependency on the chirality of the respective P^N ligand was found, whereas the specific kind and size of the different substituents has only a minor impact on the properties in solution. Most importantly, all complexes except C3 are photostable in solution and show fully reversible redox processes. Sacrificial reductants were applied to demonstrate a successful electron transfer upon light irradiation. These properties render this class of photosensitizers as potential candidates for solar energy conversion issues.
- Frey, Wolfgang,Giereth, Robin,Karnahl, Michael,Klo?, Marvin,Mengele, Alexander K.,Steffen, Andreas,Tschierlei, Stefanie
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p. 2675 - 2684
(2020/03/04)
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- Design, Synthesis, Fungicidal Activity, and Unexpected Docking Model of the First Chiral Boscalid Analogues Containing Oxazolines
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Chirality greatly influences the biological and pharmacological properties of a pesticide and will contribute to unnecessary environmental loading and undesired ecological impact. No structure and activity relationship (SAR) of enantiopure succinate dehydrogenase inhibitors (SDHIs) was documented during the structure optimization of boscalids. On the basis of commercial SDHIs, oxazoline natural products, and versatile oxazoline ligands in organic synthesis, the first effort was devoted to explore the chiral SDHIs and the preliminary mechanism thereof. Fine-tuning furnished chiral nicotinamides 4ag as a more promising fungicidal candidate against Rhizoctonia solani, Botrytis cinerea, and Sclerotinia sclerotiorum, with EC50 values of 0.58, 0.42, and 2.10 mg/L, respectively. In vivo bioassay and molecular docking were investigated to explore the potential in practical application and plausible novelty in action mechanism, respectively. The unexpected molecular docking model showed the different chiral effects on the binding site with the amino acid residues. This chiral nicotinamide also featured easy synthesis and cost-efficacy. It will provide a powerful complement to the commercial SDHI fungicides with the introduction of chirality.
- Li, Shengkun,Li, Dangdang,Xiao, Taifeng,Zhang, Shasha,Song, Zehua,Ma, Hongyu
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p. 8927 - 8934
(2016/12/07)
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- Synthesis of imidacloprid derivatives with a chiral alkylated imidazolidine ring and evaluation of their insecticidal activity and affinity to the nicotinic acetylcholine receptor
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A series of imidacloprid (IMI) derivatives with an alkylated imidazolidine ring were asymmetrically synthesized to evaluate their insecticidal activity against adult female housefly, Musca domestica, and affinity to the nicotinic acetylcholine receptor of the flies. The bulkier the alkyl group, the lower was the receptor affinity, but the derivatives methylated and ethylated at the R-5-position of the imidazolidine ring were equipotent to the unsubstituted compound. Quantitative structure-activity relationship (QSAR) analysis of the receptor affinity demonstrated that the introduction of a substituent into the imidazolidine ring was fundamentally disadvantageous, but the introduction of a substituent at the R-5-position was permissible in the case of its small size. The binding model of the synthesized derivatives with the receptor supported the QSAR analysis, indicating the existence of space for a short alkyl group around the R-5-position in the ligand-binding site. In addition, positive correlation was observed between the insecticidal activity and receptor affinity, suggesting that the receptor affinity was the primary factor in influencing the insecticidal activity even if the imidazolidine ring was modified.
- Nishiwaki, Hisashi,Kuriyama, Mituhiro,Nagaoka, Hikaru,Kato, Akira,Yamauchi, Satoshi,Shuto, Yoshihiro,Akamatsu, Miki
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p. 6305 - 6312,8
(2012/12/11)
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- The first synthesis of β-amino phosphonates using cyclic sulfamidates
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Cyclic sulfamidates (prepared from α-amino acids and β-amino alcohols) have been used for the first time for the synthesis of novel β-amino phosphonates (chiral and achiral) by treatment with dialkyl phosphites using sodium hydride. 2-Substituted and 1,2-disubtituted β-amino phosphonates have efficiently been prepared following this method. The products are formed in high yield (79-84%) within 8-12 h.
- Das, Biswanath,Reddy, Cheruku Ravindra,Nagendra, Siddavatam,Lingaiah, Maram
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scheme or table
p. 3496 - 3498
(2011/07/08)
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- Enantiopure cyclic O-substituted phenylphosphonothioic acid: Synthesis and chirality-recognition ability
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As a new acidic selector (resolving agent), we synthesized an enantiopure O-alkyl phenylphosphonothioic acid with a seven-membered ring ((R)-5), which was designed on the basis of the results for the enantioseparation of 1-arylethylamine derivatives with acyclic O-ethyl phenylphosphonothioic acid (I). The phosphonothioic acid (R)-5 showed unique chirality-recognition ability in the enantioseparation of 1-naphthylethylamine derivatives, aliphatic secondary amines, and amino alcohols; the ability was complementary to that of I. The X-ray crystallographic analyses of the less- and more-soluble diastereomeric salts showed that hydrogen-bonding networks in the salt crystals are 21-column-type with a single exception which is cluster-type. In the cases of the 21-column-type crystals, stability of the crystals is firstly governed by hydrogen bonds to form a 21-column and secondly determined by intra-columnar T-shaped CH/π interaction(s), intra-columnar hydrogen bond(s), inter-columnar van der Waals interaction and/or inter-columnar T-shaped CH/π interaction(s). In contrast, the cluster-type salt crystal is stabilized by the assistance of inter-cluster T-shaped CH/π and van der Waals interactions. To realize still more numbers of intra- and inter-columnar and -cluster T-shaped CH/π interactions, the seven-membered ring of (R)-5 plays a considerable role. Copyright
- Ribeiro, Nigel,Kobayashi, Yuka,Maeda, Jin,Saigo, Kazuhiko
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experimental part
p. 438 - 448
(2012/01/02)
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- Studies of the synthesis of all stereoisomers of MG-132 proteasome inhibitors in the tumor targeting approach
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MG-132 is a tripeptide aldehyde (Z-L-leu-L-leu-L-leu-H, 2) proteasome inhibitor that exerts antitumor activity and enhances cytostatic/cytotoxic effects of chemo- and radiotherapy. Because of a troublesome synthesis of tripeptides with a non-natural configuration and modified side chains of amino acids, only two stereoisomers of MG-132 have been reported. Here, we propose a new approach to the synthesis of tripeptide aldehydes based on the Ugi reaction. Chiral, enantiomerically stable 2-isocyano-4-methylpentyl acetates were used as substrates for Ugi reaction resulting in a formation of tripeptide skeletons. Further functionalization of the obtained products led to a synthesis of tripeptide aldehydes. All stereoisomers of MG-132 were synthesized and studied as potential inhibitors of chymotrypsin-like, trypsin-like, and peptidylglutamyl peptide hydrolyzing activities of proteasome. These studies demonstrated the influence of absolute configuration of chiral aldehydes on the cytostatic/cytotoxic effects of the synthesized compounds and revealed that only (S,R,S)-(-)-2 stereoisomer is a more potent. proteasome inhibitor than MG-132.
- Mroczkiewicz, Michal,Winkler, Katarzyna,Nowis, Dominika,Placha, Grzegorz,Golab, Jakub,Ostaszewski, Ryszard
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experimental part
p. 1509 - 1518
(2010/08/03)
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- Enantioselective syntheses of morpholines and their homologues via S N2-type ring opening of aziridines and azetidines with haloalcohols
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(Chemical Equation Presented) A highly regio- and stereoselective strategy for the syntheses in high yield and enantioselectivity of a variety of substituted nonracemic morpholines and their homologues is described. The reaction proceeds via an SN2-type ring opening of activated aziridines and azetidines by suitable halogenated alcohols in the presence of Lewis acid followed by base-mediated intramolecular ring closure of the resulting haloalkoxy amine.
- Ghorai, Manas K.,Shukla, Dipti,Das, Kalpataru
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body text
p. 7013 - 7022
(2009/12/22)
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- CHEMOKINE RECEPTOR BINDING COMPOUNDS
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The present invention relates to chemokine receptor binding compounds, pharmaceutical compositions and their use. More specifically, the present invention relates to modulators of chemokine receptor activity, preferably modulators of CCR4 or CCR5. In one aspect, these compounds demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).
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Page/Page column 39
(2010/11/26)
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- Amino alcohol derivatives, method of producing said derivatives and medicaments containing them
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Compounds of formula I in which R1denotes hydrogen or methyl R2denotes lower straight-chained or branched alkyl with 1 to 10 carbon atoms R3denotes hydrogen or lower alkyl n denotes 0-12 R4denotes alkyl, alkenyl or alkinyl with 6 to 24 carbon atoms, processes for the production thereof as well as pharmaceutical agents containing these compounds for the treatment of osteoporosis.
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- Synthesis of Optically Active 1,3,2-Oxazaphospholidine 2-Sulfides and 1,3,2-Benzodioxaphosphorin 2-Sulfides
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The optical isomers of ten kinds of insecticidal 1,3,2-oxazaphospholidine 2-sulfides (OS) and two kinds of 1,3,2-benzodioxaphosphorin 2-sulfides (BS), including the commercial insecticide salithion, were synthesized in high optical purity by using two optically active aryl methyl phosphorochloridothionates (AMPC) as chiral two-step phosphorylating reagents.Their configurations were assigned according to the reaction mechanism and supported by proton NMR information.
- Wu, Shao-Yong,Hirashima, Akinori,Kuwano, Eiichi,Eto, Morifusa
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p. 537 - 548
(2007/10/02)
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- Stereochemistry and Reactions of Aziridinylphosphinothionates Derived from Amino Acids
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Aziridinylphosphinothionates were prepared from optically active ethyl hydrogen phenylphosphonothionates and 1-bromo-2-alkanamines derived from leucine or valine.The aziridine ring was opened by the action of some nucleophiles.Refluxing the aziridinylphosphinethionates in acetone with sodium iodide caused hydrolysis accompanied by the rearrangement of the sulfur atom to give β-mercaptoethylphosphonamidates.The reaction mechanism was discussed eith stereochemical considerations.The insecticidal activity of the products was also examined.
- Hirashima, Akinori,Eto, Morifusa
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p. 829 - 838
(2007/10/02)
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- Synthesis and Chemical Properties of Insecticidal 2-Alkoxy-4-alkyl-1,3,2-oxazaphospholidine 2-Sulfides Derived from Optically Active Amino Acids
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Some (4S)- and (4R)-2-alkoxy-4-alkyl-1,3,2-oxazaphospholidine 2-sulfides were prepared from optically active α-amino acids.They were mixtures of diastereoisomeric pairs, which were separated into isomers carefully by gas chromatography or thin-layer chromatography with multiple development technique.Their characteristics on NMR and mass fragmentation were determined in comparison with deuterium labeled compounds.Nucleophiles readily cleaved the five-membered ring by fission of the endocyclic P-O bond.In 2-chloro analog, however, a displacement raction on the phosphorus occurred without a ring-opening.
- Tawata, Shinkichi,Kuwano, Eiichi,Eto, Morifusa
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p. 1489 - 1498
(2007/10/02)
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