1903-22-6Relevant articles and documents
Understanding the conformational analysis of gababutin based hybrid peptides
Konda, Maruthi,Jadhav, Rohit G.,Maiti, Sayan,Mobin, Shaikh M.,Kauffmann, Brice,Das, Apurba K.
, p. 1728 - 1735 (2018)
Constrained γ-amino acid gababutin (Gbn) based peptides that form different conformations have been synthesized. Striving to rationalize the impact of side chain orientations framing tetrapeptide-based supramolecular organic frameworks and morphological entities, Gbn incorporated hybrid peptides Boc-Gbn-Aib-Aaa-Aib-OMe (where Aaa = Phe(F) for peptide 1, Leu(L) for peptide 2 and Tyr(Y) for peptide 3) were synthesized by changing the amino acid at the third position. The solution state dual folded conformation (C12/C10 H-bonded) is probed by 2D NMR spectroscopy in support of a DMSO-d6 titration and VT NMR experiments. Peptides 1-3 adopt a C12/C10 type H-bonded dual folded conformation in the crystal state. In addition, distinct supramolecular frameworks result from the modification and orientation of the third residue side chain of peptides 1-3. A solvent induced morphological diversity of peptides 1-3 is attained by modifying the side chain backbone of the tetrapeptides, which are investigated by various microscopic (SEM and AFM) studies. Gbn-based peptides 1-3 show significant morphological and supramolecular packing properties, which are fairly different from those of their gabapentin (Gpn) based analogue peptides.
Synthesis and Exploration of Abscisic Acid Receptor Agonists Against Dought Stress by Adding Constraint to a Tetrahydroquinoline-Based Lead Structure
Baltz, Rachel,Bojack, Guido,Dittgen, Jan,Fischer, Christian,Frackenpohl, Jens,Freigang, J?rg,Getachew, Rahel,Grill, Erwin,Helmke, Hendrik,Hohmann, Sabine,Lange, Gudrun,Lehr, Stefan,Porée, Fabien,Schmidt, Jana,Schmutzler, Dirk,Yang, Zhenyu
supporting information, p. 3442 - 3457 (2021/06/25)
New oxotetrahydroquinolinyl- and oxindolinyl sulfonamides interacting with RCAR/(PYR/PYL) receptor proteins were identified as lead structures against drought stress in crops starting from protein docking studies of a sulfonamide lead structure, followed by in-depth SAR studies. Optimized five to six step synthetic approaches via substituted amino oxo-tetrahydro-quinolines and amino oxo-indolines as essential intermediates gave access to the envisaged oxo-tetrahydroquinolinyl and oxindolinyl sulfonamides. Whilst oxo-tetrahydroquinolinyl sulfonamides with additional carbon substituents or spiro-cycloalkyl groups exhibited only low to moderate target affinities, the corresponding spiro-oxindolinyl and oxo-tetrahydroquinolinyl sulfonamides carrying optimized N-substituents revealed strong interactions with RCAR/(PYR/PYL) receptor proteins in Arabidopsis thaliana. Remarkably, the in vitro activity observed for these new compounds was on the same level as observed for the naturally occurring plant hormone in line with strong efficacy against drought stress in-vivo (canola and wheat as broad-acre crops).
INHIBITORS OF MICROBIALLY INDUCED AMYLOID
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Paragraph 0001032-0001033, (2021/07/17)
The present disclosure provides compounds useful for the prevention of amyloid formation and the treatment of amyloid related disorders, including synucleopathies such as Parkinson's Disease.
Visible-Light Mediated Hydrosilylative and Hydrophosphorylative Cyclizations of Enynes and Dienes
Chen, Xiaoyun,Hou, Hong,Shi, Yaocheng,Xu, Yue,Yan, Chaoguo,Yang, Haibo,Zhu, Shaoqun
supporting information, (2020/03/04)
Described herein is a visible-light mediated intermolecular radical cyclization approach to access heterocycles. Heteroatom radicals, such as silicon and phosphorus atom radicals, were generated via direct hydrogen atom abstraction by the photoexcited catalyst species with hydro-silanes and phosphine oxides. The radical addition/cyclization/HAT (hydrogen atom transfer) reaction sequences of 1,6-enynes and 1,6-dienes were highly efficient delivering the desired heterocycles in good yields.
Visible-Light-Promoted Intramolecular α-Allylation of Aldehydes in the Absence of Sacrificial Hydrogen Acceptors
Liu, Feng,Liu, Jia-Li,tu, Jia-Lin
supporting information, p. 7369 - 7372 (2020/10/05)
We report herein an unprecedented protocol for radical cyclization of aldehydes with pendant alkenes via synergistic photoredox, cobaloxime, and amine catalysis. The transformation was achieved in the absence of external oxidants, providing a variety of 5-, 6-, and 7-membered ring products with alkene transposition in satisfactory yields. The reaction exhibits wide functional group compatibility and occurs under mild conditions with extrusion of H2.
Synthesis of novel shikonin derivatives and pharmacological effects of cyclopropylacetylshikonin on melanoma cells
Durchschein, Christin,Bauer, Rudolf,Kretschmer, Nadine,Hufner, Antje,Rinner, Beate,Stallinger, Alexander,Deutsch, Alexander,Lohberger, Birgit
supporting information, (2018/11/23)
Despite much research in the last centuries, treatment of malignant melanoma is still challenging because of its mostly unnoticeable metastatic spreading and aggressive growth rate. Therefore, the discovery of novel drug leads is an important goal. In a previous study, we have isolated several shikonin derivatives from the roots of Onosma paniculata Bureau & Franchet (Boraginaceae) which evolved as promising anticancer candidates. β,β-Dimethylacrylshikonin (1) was the most cytotoxic derivative and exhibited strong tumor growth inhibitory activity, in particular, towards melanoma cells. In this study, we synthesized eighteen novel shikonin derivatives in order to obtain compounds which exhibit a higher cytotoxicity than 1. We investigated their cytotoxic potential against various melanoma cell lines and juvenile skin fibroblasts. The most active compound was (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl cyclopropylacetate (cyclopropylacetylshikonin) (6). It revealed significant stronger tumor growth inhibitory activity towards two melanoma cell lines derived from metastatic lesions (WM164 and MUG-Mel2). Further investigations have shown that 6 induced apoptosis caspase-dependently, increased the protein levels of cleaved PARP, and led to double-stranded DNA breaks as shown by phosphorylation of H2AX. Cell membrane damage and cell cycle arrest were not observed.
USE OF SUBSTITUTE OXO TETRAHYDROQUINOLINE SULFONAMIDES OR SALTS THEREOF FOR RAISING STRESS TOLERANCE OF PLANTS
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Paragraph 0199, (2017/02/28)
The invention relates to the use of substituted oxotetrahydroquinolinylsulfonamides or salts thereof where the radicals in the general formula (I) correspond to the definitions given in the description, for enhancing stress tolerance in plants to abiotic stress, and/or for increasing plant yield.
Copper-Catalyzed Enantio-, Diastereo-, and Regioselective [2,3]-Rearrangements of Iodonium Ylides
Xu, Bin,Tambar, Uttam K.
supporting information, p. 9868 - 9871 (2017/08/08)
The first highly enantioselective, diastereoselective, and regioselective [2,3]-rearrangement of iodonium ylides has been developed as a general solution to catalytic onium ylide rearrangements. In the presence of a chiral copper catalyst, substituted allylic iodides couple with α-diazoesters to generate metal-coordinated iodonium ylides, which undergo [2,3]-rearrangements with high selectivities (up to >95:5 r.r., up to >95:5 d.r., and up to 97 % ee). The enantioenriched iodoester products can be converted stereospecifically into a variety of onium ylide rearrangement products, as well as compounds that are not accessible by classical onium ylide rearrangements.
The synthesis of α,α-disubstituted α-amino acids via ichikawa rearrangement
Szczes?niak, Piotr,Pieczykolan, Micha?,Stecko, Sebastian
, p. 1057 - 1074 (2016/02/19)
An approach to α,α-disubstituted α-amino acids is reported. The key step is allyl cyanate-to-isocyanate rearrangement. As demonstrated, the resultant allyl isocyanates can be directly trapped with various nucleophiles, for instance, alcohols, amines, and organometallic reagents, to provide a broad range of N-functionalized allylamines. The developed method has been successfully applied in the synthesis of two bioactive peptides: 2-aminoadamantane-2-carboxylic acid derived P2X7-evoked glutamate release inhibitor and 4-amino-tetrahydropyranyl-4-carboxylic acid derived dipeptide GSK-2793660, which is currently in clinical trials as cathepsin C inhibitor for the treatment of cystic fibrosis, noncystic fibrosis bronchiectasis, ANCA-associated vasculitis and bronchiectasis.
Titanium(IV) Chloride-Mediated Stereoselective α-Alkylidenation to Efficiently Assemble Multisubstituted 1,3-Dienes
Sun, Rengwei,Song, Wei,Ma, Chunmei,Zhang, Huiwen,Yu, Xinhong
supporting information, p. 3977 - 3982 (2016/12/30)
A direct access to multisubstituted 1,3-dienes by α-exclusive alkylidenation of crotonic derivatives has been developed. This protocol, mediated by titanium tetrachloride chelation, features excellent regio- and stereoselectivity, mild reaction conditions, easy operation and wide substrate scope. Conversions of the derived dienes to other useful molecules were also explored. (Figure presented.).
