82353-56-8Relevant academic research and scientific papers
Studies towards the synthesis of superstolide A. Synthesis and stereochemical assignment of the C(21)-C(26) fragment of superstolide A
Zampella, Angela,D'Auria, Maria Valeria
, p. 1543 - 1545 (2001)
An asymmetric synthesis of the C(21)_C(26) fragment of superstolide A is described. A fragment, corresponding to a reductive ozonolysis product of superstolide, was also prepared. Comparison of spectroscopic and optical properties of the corresponding fragment obtained by degradation of natural superstolide A allowed the confirmation of the stereochemistry of the natural product.
The first synthesis of Crucigasterin 277—a polyunsaturated C-18 amino alcohol from the Mediterranean tunicate Pseudomonas crucigaster
Flock, Solveig,Antonsen, Simen,Gallantree-Smith, Harrison,Langseter, Anne Marie,Skatteb?l, Lars,Stenstr?m, Yngve
, p. 4518 - 4522 (2016)
Starting from eicosapentaenoic acid (EPA) and D-alanine, the first synthesis of (2R, 3S)-crucigasterin 277, a polyunsaturated C-18 amino alcohol from the Mediterranean tunicate, Pseudodistoma crucigaster, is described.
SYNTHESES AND ABSOLUTE CONFIGURATIONS OF THE CYTOKININS 1'-METHYLZEATIN AND ITS 9-RIBOSIDE
Itaya, Taisuke,Fujii, Tozo,Evidente, Antonio,Randazzo, Giacomino,Surico, Giuseppe,Iacobellis, Nicola S.
, p. 6349 - 6352 (1986)
On the basis of the chiral syntheses of (1'R)-I and (1'S)-I and of their 9-ribosides (1''R)-III and (1''S)-III from D- and L-alanines, the structures of the cytokinins 1'-methylzeatin and its 9-riboside have been established to be (1'R)-I and (1''R)-III.
Discovery of DS79932728: A Potent, Orally Available G9a/GLP Inhibitor for Treating β-Thalassemia and Sickle Cell Disease
Katayama, Katsushi,Ishii, Ken,Terashima, Hideki,Tsuda, Eisuke,Suzuki, Makoto,Yotsumoto, Keiichi,Hiramoto, Kumiko,Yasumatsu, Isao,Torihata, Munefumi,Ishiyama, Takashi,Muto, Tsuyoshi,Katagiri, Takahiro
supporting information, p. 121 - 128 (2021/01/14)
Therapeutic reactivation of the γ-globin genes for fetal hemoglobin (HbF) production is an attractive strategy for treating β-thalassemia and sickle cell disease. It was reported that genetic knockdown of the histone lysine methyltransferase EHMT2/1 (G9a/GLP) is sufficient to induce HbF production. The aim of the present work was to acquire a G9a/GLP inhibitor that induces HbF production sufficiently. It was revealed that tetrahydroazepine has versatility as a side chain in various skeletons. We ultimately obtained a promising aminoindole derivative (DS79932728), a potent and orally bioavailable G9a/GLP inhibitor that was found to induce γ-globin production in a phlebotomized cynomolgus monkey model. This work could facilitate the development of effective new approaches for treating β-thalassemia and sickle cell disease.
Synthesis and Characterization of Optically Pure Gamma-PNA Backbones by SIBX-Mediated Reductive Amination
Periyalagan, Alagarsamy,Kim, Yong-Tae,Hong, In Seok
, p. 1304 - 1309 (2021/08/09)
Chiral peptide nucleic acid (PNA) is a derivative of regular PNA by introducing a chiral center to its backbone, and is known to bind more strongly to DNA or RNA than regular PNA. In particular, in the case of a γ-backbone, the L isomer stabilizes the PNA/DNA duplex, and the D-isomer has the opposite effect. Therefore, the synthesis of an optically pure γ-backbone is very important. Here, we report a novel synthetic strategy for the suppression of epimerization during the synthesis of the γ-PNA backbone. A stabilized form of 2-iodoxybenzoic acid (SIBX) was used as an oxidative reagent in the key intermediate of the N-Boc-amino acetaldehyde synthesis. This paper reports (1) the synthesis and comparison of three different γ-PNA backbones (lysine, alanine, and glutamate) by three different synthetic routes (SIBX, lithium aluminum hydride, and Red-Al) and (2) the determination of chiral purity from their derivative compounds. The enantiomeric excess purity of SIBX-mediated γ-PNA backbones was determined to be more than 99.4%, as ascertained by the high-performance liquid chromatography (HPLC) chromatogram on a standard RP-C18 column. It is comparatively higher than that of the other methods examined in this work.
Structure-activity relationship studies on the inhibition of the bacterial translation of novel Odilorhabdins analogues
Cao, Sha,Gualtieri, Maxime,Hjort, Karin,Hughes, Diarmaid,Huseby, Douglas L,Ikaunieks, Martins,Katkevics, Martins,Kukosha, Tatyana,Loza, Einars,Pantel, Lucile,Racine, Emilie,Ryabova, Victoria,Sarciaux, Matthieu,Serri, Marine,Shubin, Kirill,Suna, Edgars,Trufilkina, Nadezhda,Yadav, Kavita
, (2020/04/15)
A structure–activity relationship (SAR) study of NOSO-95179, a nonapeptide from the Odilorhabdin class of antibacterials, was performed by systematic variations of amino acids in positions 2 and 5 of the peptide. A series of non-proteinogenic amino acids was synthesized in high enantiomeric purity from Williams’ chiral diphenyloxazinone by highly diastereoselective alkylation or by aldol-type reaction. NOSO-95179 analogues for SAR studies were prepared using solid-phase peptide synthesis. Inhibition of bacterial translation by each of the synthesized Odilorhabdin analogues was measured using an in vitro test. For the most efficient analogues, antibacterial efficacy was measured against two wild-type Enterobacteriaceae (Escherichia coli and Klebsiella pneumoniae) and against an efflux defective E. coli strain (ΔtolC) to evaluate the impact of efflux on the antibacterial activity.
Chiral 1,5-disubstituted 1,2,3-triazoles-versatile tools for foldamers and peptidomimetic applications
Beke-Somfai, Tamás,Johansson, Johan R.,Kann, Nina,Paterson, Andrew J.,Said St?lsmeden, Anna,Szigyártó, Imola Cs.,Thunberg, Linda
, p. 1957 - 1967 (2020/03/23)
1,4- A nd 1,5-Disubstituted triazole amino acid monomers have gained increasing interest among peptidic foldamers, as they are easily prepared via Cu- A nd Ru-catalyzed click reactions, with the potential for side chain variation. While the latter is key to their applicability, the synthesis and structural properties of the chiral mono-or disubstituted triazole amino acids have only been partially addressed. We here present the synthesis of all eight possible chiral derivatives of a triazole monomer prepared via a ruthenium-catalyzed azide alkyne cycloaddition (RuAAC). To evaluate the conformational properties of the individual building units, a systematic quantum chemical study was performed on all monomers, indicating their capacity to form several low energy conformers. This feature may be used to effect structural diversity when the monomers are inserted into various peptide sequences. We envisage that these results will facilitate new applications for these artificial oligomeric compounds in diverse areas, ranging from pharmaceutics to biotechnology.
BET INHIBITORS FOR MODULATING DUX4 EXPRESSION IN FSHD
-
Page/Page column 159, (2020/07/14)
The present disclosure provides BET inhibitors of the formula: wherein the variables are defined herein, as well as pharmaceutical compositions thereof. The present disclosure also provides methods of treating a patient comprising administering a bromo- and extra-terminal (BET) domain inhibitor for the treatment of FSHD which modulates DUX4 expression. In some embodiments, the present methods comprise using one or more BET inhibitors as a therapeutic agent for the treatment of FSHD patients including patients who are being treated with one or more palliative treatments such as therapy and/or agents which lead to increased muscle mass.
TYK2 INHIBITORS AND USES THEREOF
-
Paragraph 00465, (2020/09/27)
Described herein are compounds that are useful in treating a TYK2-mediated disorder. In some embodiments, the TYK2-mediated disorder is an autoimmune disorder, an inflammatory disorder, a proliferative disorder, an endocrine disorder, a neurological disorder, or a disorder associated with transplantation.
Structure–Activity Relationships of Antiplasmodial Pantothenamide Analogues Reveal a New Way by Which Triazoles Mimic Amide Bonds
Guan, Jinming,Tjhin, Erick T.,Howieson, Vanessa M.,Kittikool, Tanakorn,Spry, Christina,Saliba, Kevin J.,Auclair, Karine
supporting information, p. 2677 - 2683 (2018/12/11)
Pantothenamides are potent growth inhibitors of the malaria parasite Plasmodium falciparum. Their clinical use is, however, hindered due to the ubiquitous presence of pantetheinases in human serum, which rapidly degrade pantothenamides into pantothenate and the corresponding amine. We previously reported that replacement of the labile amide bond with a triazole ring not only imparts stability toward pantetheinases, but also improves activity against P. falciparum. A small library of new triazole derivatives was synthesized, and their use in establishing structure–activity relationships relevant to antiplasmodial activity of this family of compounds is discussed herein. Overall it was observed that 1,4-substitution on the triazole ring and use of an unbranched, one-carbon linker between the pantoyl group and the triazole are optimal for inhibition of intraerythrocytic P. falciparum growth. Our results imply that the triazole ring may mimic the amide bond with an orientation different from what was previously suggested for this amide bioisostere.
