- 188. Bestimmung des Chiralitaetssinns der enantiomeren 2,6-Adamantandiole
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The enantiomers of 2,6-adamantanediol (1) are resolved via the diastereoisomeric camphanoates.The (2R,6R)-chirality sense for (-)-1 and (2S,6S) for (+)-1 was determined by chemical correlation with (-)-(1R,5R)-bicyclononan-2,6-dion((1R,5R)-3) of known absolute configuration in the following way: alkylation of the bis(pyrrolidine enamine) of (-)-(1R,5R)-3 with CD2I2 and hydrolysis of the product gives the enantiomer 4 of (4,4-D2)-2,6-adamantanedione.Reduction of 4 with LiAlH4 leads to one enantiomer (Scheme 2) of each of the three diols 5-7 of known absolute configuration.The three diols are themselves configurational isomers due to the presence of the CD2 group, but correspond otherwise entirely to the enantiomeric diols 1.Accordingly, they can also be separated by means of their diastereoisomeric camphanoates to give the diols 5/6 and 7.These samples are easily distinguished and identified by their characteristic 1H-NMR spectra (cf.Fig. 2.).This allows to identify the (2R,6R)- and (2S,6S)-enantiomer of 1 on the basis of their behaviour in the resolution experiment analogous to that of the diols 5/6 and 7, respectively.The diol (-)-1 must have the (2R,6R)-configuration because it forms, like the diols 5/6, with (-)-camphanic acid the diastereoisomeric ester less soluble in benzene.The diol (+)-1 has (2S,6S)-configuration, because it forms, like 7, with (+)-camphanic acid the diastereoisomeric ester less soluble in benzene.The bis(4-methoxybenzoate) of (-)-(2R,6R)-1 shows chiroptical properties which are in accordance with Nakanishi's rule for two chromophores having coupled electric dipol transition moments arranged with a left handed torsion angle.
- Gerlach, Hans
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- Chiral bisphosphine ligands based on quinoline oligoamide foldamers: application in asymmetric hydrogenation
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A series of chiral bisphosphine ligands were designed and synthesized based on single-handed quinoline oligoamide foldamers. The bisphosphine ligands can coordinate with Rh(cod)2BF4 in a 1 : 1 stoichiometry and the resulted chiral Rh(i) catalysts were applied in the asymmetric hydrogenation of α-dehydroamino acid esters, in which excellent conversions and promising levels of enantioselectivity were achieved.
- Zheng, Lu,Zheng, Dan,Wang, Yanru,Yu, Chengyuan,Zhang, Kun,Jiang, Hua
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supporting information
p. 9573 - 9577
(2019/11/20)
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- Irreversible Cysteine-Selective Protein Labeling Employing Modular Electrophilic Tetrafluoroethylation Reagents
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Fluoroalkylation reagents based on hypervalent iodine are widely used to transfer fluoroalkyl moieties to various nucleophiles. However, the transferred groups have so far been limited to simple structural motifs. We herein report a reagent featuring a secondary amine that can be converted to amide, sulfonamide, and tertiary amine derivatives in one step. The resulting reagents bear manifold functional groups, many of which would not be compatible with the original synthetic pathway. Exploiting this structural versatility and the known high reactivity toward thiols, the new-generation reagents were used in bioconjugation with an artificial retro-aldolase, containing an exposed cysteine and a reactive catalytic lysine. Whereas commercial reagents based on maleimide and iodoacetamide labeled both sites, the iodanes exclusively modified the cysteine residue. The study thus demonstrates that modular fluoroalkylation reagents can be used as tools for cysteine-selective bioconjugation.
- Václavík, Ji?í,Zschoche, Reinhard,Klimánková, Iveta,Matou?ek, Václav,Beier, Petr,Hilvert, Donald,Togni, Antonio
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supporting information
p. 6490 - 6494
(2017/05/15)
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- Asymmetric (4+3) cycloadditions of enantiomerically enriched epoxy enolsilanes
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A f(oxy) allyl: The intermolecular (4+3) cycloaddition of enantiomerically enriched epoxy enolsilanes produces cycloadducts with up to 99 % ee, thus implying the reaction does not proceed by the putative achiral oxyallyl cation intermediate, but through a transiently chiral electrophile which retains the stereochemical information of the epoxide (see scheme; TES=triethylsilyl, Tf=trifluoromethanesulfonyl). Copyright
- Lo, Brian,Lam, Sarah,Wong, Wing-Tak,Chiu, Pauline
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supporting information
p. 12120 - 12123
(2013/01/16)
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- Synthesis and resolution of 2,2-dimethyl-1,3-diphenyl-1,3-propanediol, a new C2-symmetric and conformationally rigid acyclic diol
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Diastereomerically pure (+)- and (-)-2,2-dimethyl-1,3-diphenyl-1,3-propanediols were synthesized starting from diethyl malonate and resolved through diesters of (-)-camphanic acid and also N-carbethoxy-L-proline. The absolute configuration of the (-)-enantiomer was established by X-ray crystallography.
- Bhowmick,Prasad,Joshi
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p. 851 - 855
(2007/10/03)
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- 6-Acylamino-2-[(ethylsulfonyl)oxy]-1H-isoindole-1,3-diones mechanism-based inhibitors of human leukocyte elastase and cathepsin G: Effect of chirality in the 6-acylamino substituent on inhibitory potency and selectivity
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Inhibition of human leukocyte elastase(HLE) by a series of 6-acylamino-2-[(ethylsulfonyl)oxy)]-1H-isoindole-1,3-diones was determined and compared to their inhibition of ChT, PPE, and Cat G. The best inhibitor of the series was 6-((1′S)-camphanyl)amino-2-[(ethylsulfonyl)oxy]-1H-isoindole-1,3-dione 5b, with a kobs/[I]=11,000M-1 s-1. This study revealed that HLE shows a preference for the S stereochemistry and tolerates hydrophobic substituents in the Sn′ binding sites. Molecular modeling of noncovalent HLE-inhibitor complexes was used as a tool to investigate our binding model. Buffer stability assays reveal that these compounds are susceptible to hydrolysis at physiological pH. Copyright
- Vagnoni, Lisa M.,Gronostaj, Michael,Kerrigan, John E.
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p. 637 - 645
(2007/10/03)
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- Conformational study of α-arylethylamides of (-)-camphanic acid
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The absolute conformation and configuration of diastereomeric amides (4A,B-6A,B) of (1S,3R)-camphanic acid (lactone of 1-hydroxy-2,2,3- trimethylcyclopentan-1,3-dicarboxylic acid, (-)-camphanic acid 9) with α- arylethylamines 1-3 are deduced from 1H NMR data and MM2 calculations. The α-arylethyl group in diastereomers A and B adopt nearly opposite absolute conformations, stabilized by hydrogen bonding in the syn-oriented O-C(1)- C(6)-N-H unit, and repulsive interaction between the 1'C-Me group and the amide C=O group. The absolute configuration (1'S) is assigned to the 4A-6A diastereomers, and the (1'R)-configuration to the 4B-6B diastereomers; this assignment is confirmed by the preparation of 4A and 5A from enantiomerically pure (1'S)-α-arylethylamines 1 and 2, respectively. These results also enabled the assignment of pro-R (H(R)) and pro-S (H(S)) protons in the benzyl derivative 7.
- Hamersak, Zdenko,Selestrin, Ana,Lesac, Andreja,Sunjic, Vitomir
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p. 1891 - 1897
(2007/10/03)
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- Chemistry of the mycalamides: Antiviral and antitumour compounds from a New Zealand marine sponge. Part 6. The synthesis and testing of analogues of the C(7)-C(10) fragment
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The key structural features associated with the potent cytotoxicity observed in the mycalamide, onnamide, pederin and theopederin series have been defined on the basis of structure-activity studies. A model pharmacophore structure has been proposed and selected examples, with modest bioactivity, synthesized.
- Abell, Andrew D.,Blunt, John W.,Foulds, Glenn J.,Munro, Murray H. G.
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p. 1647 - 1654
(2007/10/03)
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- Synthesis of optically active myo-inositol derivatives starting from phytic acid
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Phytic acid treated with Baker's yeast gave D-myo-inositol-1,2,6-tris(phosphate) (α-trinositol) which was transformed into (+)-D-1,2-O-isopropylidene-myo-inositol and (-)-D-4,5-tri- O-benzyl-myo-inositol, two key intermediates in the synthesis of optically active myo-inositol derivatives and related compounds.
- Blum, Corinne,Rehnberg, Nicola,Spiess, Bernard,Schlewer, Gilbert
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p. 163 - 168
(2007/10/03)
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- Asymmetric synthesis and enantiospecificity of binding of 2-(1,2,3,4-tetrahydro-1-isoquinolyl)-ethanol derivatives to μ and κ receptors
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A number of 2-(1,2,3,4-tetrahydro-1-isoquinolyl)-ethanol derivatives 7a-e have been synthesized in diastereomerically and enantiomerically pure form and have been evaluated for their binding affinity at μ and κ opioid receptors. The amido ketones 5a-c and ent-5a-c, which were accessible by employing 3b and ent-3b for Asymmetric Electrophilic Amidoalkylation reactions, served as starting compounds. Upon reduction of 5a-c and ent-5a-c the amido alcohols l-6a-c, u-6a-c, ent-l-6a-c and ent-u-6a-c were obtained. Hydrolysis of these compounds yielded the secondary amino alcohols l-7a-c, u-7a-c, ent-l-7a-c and ent-u-7a-c and upon reductive methylation of l-7b-c, u-7b-c, ent-l-7b-c and ent-u-7b-c with CH2O and NaCNBH3 the tertiary amino alcohols l-7d-e, u-7d-e, ent-l-7d-e and ent-u-7d-e were obtained. The binding affinities of the final compounds l-7a-e, u-7a-e, ent-l-7a-e and ent-u-7a-e at both the μ and the κ receptor were strongly dependent on their stereochemistry. In each case isomers exhibited higher affinity at the μ than at the κ receptor. For the secondary amino alcohols 7a-c the affinity at the μ receptor followed the stereochemical order l-7 > ent-l-7 > ent-u-7 > u-7 whereas for the tertiary amino alcohols the order l-7 > u-7 > ent-l-7 > ent-u-7 was found. The stereoisomers l-7d and l-7e of the tertiary amino alcohols were found to be the most active compounds the latter exhibiting a K(i) value of 7.17 which is close to that of Morphine (K(i) 1.64). In an in vivo model, the Writhing Test, both compounds l-7d and l-7e displayed high analgetic activity.
- Wanner, Klaus Th.,Praschak, Ilona,Hoefner, Georg,Beer, Herbert
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- Synthetic Microbial Chemistry, XXVI. - Absolute Configuration of (+)-Xanthocidin as Determined by the Synthesis of Its Enantiomers of Known Stereochemistry
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The absolute configuration of the antibiotic (+)-xanthocidin (4,5-dihydroxy-5-isopropyl-4-methyl-2-methylene-3-oxocyclopentane-1-carboxylic acid, 1) was shown to be 1R,4S,5S by the synthesis of its enantiomers.Lipase AK (Amano) was used for the key resolution step, and the absolute configuration of the resolved intermediate (+)-16 was determined by X-ray analysis of its (1S)-camphanic ester (+)-20. - Key Words: Antibiotics / Asymmetric acylation / Lipases / Streptomyces xanthocidicus / Xanthocidin
- Mori, Kenji,Horinaka, Akio,Kido, Masaru
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p. 817 - 826
(2007/10/02)
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- Preparation of (-)-(1S,4R)-Camphanoyl Chloride heptane-1-carbonyl Chloride, 4,7,7-Trimethyl-3-oxo, (1S)->
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A convenient three step procedure for the preparation of (-)-(1S,4R)-camphanoyl chloride, starting from (+)-camphoric acid (A) via (-)-bromocamphoric anhydride (B) and (-)-camphanic acid (C) is described.
- Kappes, Dag,Gerlach, Hans
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p. 581 - 587
(2007/10/02)
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- Stereoisomeric Flavor Substances, XII. - 3-Methyl-4-octanolide - "Quercuslactone, Whiskylactone" - Structure and Properties of the Stereoisomeres
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Ethyl 3-methyl-4-oxooctanoate (2) has been synthesized by reaction of pentanal with ethyl crotonate.Reduction with NaBH4 and cyclization yields racemic cis/trans-3-methyl-4-octanolide 1 which is separated to racemic cis (1a*1a') and trans (1b*1b') isomers by liquid chromatography.From 1a*1a' and 1b*1b' the diastereomers isopropyl (3R,4R)-, (3S,4S)-, (3S,4R)-, and (3R,4S)-4--3-methyloctanoates (3-6) and the diastereomers isopropyl (3R,4R)-, (3S,4S)-, (3S,4R)-, and (3R,4S)-4--3-methyloctanoates (7-10) have been synthesized and then separated by liquid chromatography.The absolute configurations of 1a, 1a', 1b and 1b' were derived from 1H-NMR data of 3-6 and optical activity could be estimated after recyclization into the optically active lactones 1a, 1a', 1b, and 1b'.From 7-10 optically pure stereoisomers of 1 have been obtained in preparative scale.Sensory characteristics of the stereoisomers are given.
- Guenther, Claus,Mosandl, Armin
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p. 2112 - 2122
(2007/10/02)
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