- Synthesis and Cytotoxicity Evaluation of C4- and C5-Modified Analogues of the α,β-Unsaturated Lactone of Pironetin
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Pironetin is a natural product with potent antiproliferative activity that forms a covalent adduct with α-tubulin via conjugate addition into the natural product's α,β-unsaturated lactone. Although pironetin's α,β-unsaturated lactone is involved in its binding to tubulin, the structure–activity relationship at different positions of the lactone have not been thoroughly evaluated. For a systematic evaluation of the structure–activity relationships at the C4 and C5 positions of the α,β-unsaturated lactone of pironetin, twelve analogues of the natural product were prepared by total synthesis. Modifying the stereochemistry at the C4 and/or C5 positions of the α,β-unsaturated lactone of pironetin resulted in loss of antiproliferative activity in OVCAR5 ovarian cancer cells. While changing the C4 ethyl substituent with groups such as methyl, propyl, cyclopropyl, and isobutyl were tolerated, groups with larger steric properties such as an isopropyl and benzyl groups were not.
- Huang, David S.,Wong, Henry L.,Georg, Gunda I.
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- Chiral auxiliaries as docking/protecting groups in biohydroxylation: (S)-specific hydroxylation of enantiopure tert-butyl-substituted spirooxazolidines derived from cyclopentanone
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An enantiopure tert-butyl-substituted derivative of cyclopentanone, which is a vital member of the chiral docking/ protecting group series, is employed, for the first time, to stereoselectively (90% de) introduce an (S)-configured hydroxyl group onto an unactivated carbon atom present in the cyclopentane ring using the fungus Beauveria bassiana ATCC 7159. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.
- Muenzer, Dieter F.,Griengl, Herfried,Moumtzi, Alexandra,Saf, Robert,Terzani, Tullio,De Raadt, Anna
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- Total Synthesis of the Alleged Structure of Crenarchaeol Enables Structure Revision**
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Crenarchaeol is a glycerol dialkyl glycerol tetraether lipid produced exclusively in Archaea of the phylum Thaumarchaeota. This membrane-spanning lipid is undoubtedly the structurally most sophisticated of all known archaeal lipids and an iconic molecule in organic geochemistry. The 66-membered macrocycle possesses a unique chemical structure featuring 22 mostly remote stereocenters, and a cyclohexane ring connected by a single bond to a cyclopentane ring. Herein we report the first total synthesis of the proposed structure of crenarchaeol. Comparison with natural crenarchaeol allowed us to propose a revised structure of crenarchaeol, wherein one of the 22 stereocenters is inverted.
- Cunha, Ana V.,Havenith, Remco W. A.,Holzheimer, Mira,Minnaard, Adriaan J.,Schouten, Stefan,Sinninghe Damsté, Jaap S.
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supporting information
p. 17504 - 17513
(2021/07/06)
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- HEPATITIS B VIRUS SURFACE ANTIGEN INHIBITOR
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Disclosed in the present invention is a new 11-oxo-7,11-dihydro-6h-benzo-[f]pyrido[1,2-d][1,4]azepine oxepin-10-carboxylic acid derivative serving as a hepatitis B virus surface antigen inhibitor. Specifically disclosed are a compound represented by formula (V) or a pharmaceutically acceptable salt thereof, and applications of the compound represented by formula (V) or the pharmaceutically acceptable salt thereof and a pharmaceutical composition thereof in the treatment of viral hepatitis B.
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Paragraph 0151; 0152; 0153; 0292
(2020/04/21)
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- Cr/Ni-catalyzed vinylation of aldehydes: A mechanistic study on the catalytic roles of nickel and chromium
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The roles of nickel and chromium catalysts in the coupling reaction of vinyl halides and aldehydes, the so-called Nozaki-Hiyama-Kishi (NHK) reaction, have been studied by UV/Vis spectroscopy, electrochemical, and spectroelectrochemical methods. Electrochemical studies revealed that nickel plays the central role in activating the vinyl halide by reductive cleavage, to form a rapidly decomposing vinyl-Ni species. The latter can, however, be stabilized in the presence of the Cr complex. The redox behavior of the Ni complexes in the presence of vinyl halide demonstrated that the vinyl halide activation results from interaction with a one-electron reduced nickel species [formally NiI], not necessarily with a Ni0 species. It was furthermore shown by UV/Vis spectroscopy and spectroelectrochemical methods that low-valent nickel [Ni0] results from the interaction of the NiII catalyst with CrCl2. It takes two to tango! The initial stages of the Cr/Ni-catalyzed vinylation of aldehydes (the Nozaki-Hiyama-Kishi reaction) were analyzed by electrochemical methods. The role of low-valent nickel in the C-halogen(Hal) cleavage of the vinyl halide was established, as well as the generation of the former from NiII and CrII. Copyright
- Harnying, Wacharee,Kaiser, Andre,Klein, Axel,Berkessel, Albrecht
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experimental part
p. 4765 - 4773
(2011/06/19)
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- Asymmetric synthesis of protected 1,2-amino alcohols using tert-butanesulfinyl aldimines and ketimines
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tert-Butanesulfinyl aldimines and ketimines bearing an α-benzyloxy or α-silyloxy substituent serve as precursors in the synthesis of protected 1,2-amino alcohols in high yields and diastereoselectivities. General protocols are described for the addition of unbranched alkyl, branched alkyl, and aryl organometallic reagents to N-sulfinyl aldimines 1 and 2 and ketimines 5 and 6. Furthermore, the selective N- or O-deprotection of sulfinamide products 3, 4, 7, and 8 is described, enabling further synthetic transformations of the reaction products.
- Tang,Volkman,Ellman
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p. 8772 - 8778
(2007/10/03)
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- Method of producing optically active tert-leucinol and its use
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A method of producing optically active tert-leucinol (formula I) of high enantiomeric purity STR1 by converting racemic (RS)-tert-leucinol into a diastereomeric salt pair by reaction with an optically active acid, removing the salt pair from solution by fractionated crystallization and separating therefrom the optically active acid to release the optically active tert-leucinol from the salt. The optically active acid used is an N-acylated tert-leucine of general formula VIII: STR2 in which R can be hydrogen or an alkyl-, arylalkyl- or aryl group with up to 20 C atoms and * signifies a chirality center.
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- Synthesis of (R)-tert-Leucinol by Classical Resolution of the Racemic Mixture
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Optically active tert-leucinol is an important building block in asymmetric synthesis.However, the (R) enantiomer particularly has so far remained difficult to obtain, mainly because of the laborious synthesis of the precursor amino acid, (R)-tert-leucine.Here we present a new, classical resolution of racemic tert-leucinol, which allows straightforward preparation of each, but especially the (R) enantiomer, in good yields and high optical purities.The feasibility of the synthesis of useful derivatives is demonstrated by transformation into the corresponding (R)-4-tert-butyl-2-oxazolidinone. - Keywords: amino alcohols; asymmetric syntheses; chiral auxiliaries; enantiomeric resolution
- Drauz, Karlheinz,Jahn, Wilfried,Schwarm, Michael
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p. 538 - 540
(2007/10/03)
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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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