917877-01-1Relevant articles and documents
MONOBACTAM COMPOUNDS AND USE THEREFOR
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, (2022/01/12)
Monobactam compounds and a use therefor. Specifically provided are chemical compounds represented by formula (I) or isomers, pharmaceutically acceptable salts, solvates, crystals, or prodrugs thereof, preparation methods therefor, pharmaceutical compositions containing said compounds, and a use of said compounds or compositions in treating bacterial infection. The present compounds feature excellent antibacterial activity, and have great hopes of becoming a therapeutic agent for bacterial infection.
Novel cytotoxic amphiphilic nitro-compounds derived from a synthetic route for paraconic acids
Ribeiro, Talita A.,Machado-Ferreira, Erik,Guimar?es, Lohaine F.,Cavaleiro, Jéssica,Britto, Alan Messala A.,Redua, Nátaly,de Souza, Lucas Miguel Pereira,Pimentel, André S.,Picciani, Paulo H.S.,Oliveira, Osvaldo N.,Barreto, Cléber Bonfim,Soares, Carlos Augusto G.
, (2021/06/21)
A series of precursors for bioactive paraconic acids (PA) were synthesized and their cytotoxicity assessed on human cells in vitro. Two amphiphilic nitro-containing precursors, Nitro-C15-EED and the butanolide Nitro-C12-GBL, were cytotoxic at the micromolar scale, with higher activity on tumor HeLa cells than on HEK-293T of non-tumor origin. The structure of these molecules is simple but different from reported bioactive nitro compounds. Nitro-C12-GBL was generally more cytotoxic, but after short-term (2 h) exposure both compounds reached maximum cytotoxicity. At 72 h post-treatments of HeLa cells the final dose-response for Nitro-C12-GBL (LC50 = 21.9 μmol L?1) was close to that for Nitro-C15-EED (LC50 = 25.3 μmol L?1), corresponding to LC50s ~ 3–3.6 times lower than those on HEK-293T. Short-term treatments with 50 μmol L?1 of these compounds promoted comparable outcomes, reducing tumor cells viability up to 27–36% of the controls and preserving ~70% of HEK-293T viability at 72 h post-treatments. Reduced cytotoxicity was observed in cultures continuously exposed to the compounds for longer periods (24–72 h), especially on tumor cells, underlining short-term treatments as alternatives to antiproliferative strategies. Due to their amphiphilic nature, these compounds show spontaneous surface activity and adsorption onto Langmuir monolayers of dipalmitoyl phosphatidyl choline (DPPC), especially Nitro-C12-GBL. The effects on DPPC monolayers are indicative of a possible physiological action that depends on the interaction with the cell membranes. Coarse-grained molecular dynamics indicate that individualized molecules of Nitro-C15-EED and the less toxic PA precursors are susceptible to trapping into phospholipid films. In contrast, Nitro-C12-GBL consistently forms large aggregates with outward polar domains, which could favor interaction with phospholipid polar heads of biological membranes.
Total Synthesis of a Mycolic Acid from Mycobacterium tuberculosis
Buter, Jeffrey,Fodran, Peter,Jayaraman, Dhineshkumar,Minnaard, Adriaan J.,Moody, D. Branch,Ocampo, Tonatiuh A.,Tahiri, Nabil,Van Rhijn, Ildiko,Witte, Martin D.
supporting information, p. 7555 - 7560 (2020/03/23)
In Mycobacterium tuberculosis, mycolic acids and their glycerol, glucose, and trehalose esters (“cord factor”) form the main part of the mycomembrane. Despite their first isolation almost a century ago, full stereochemical evaluation is lacking, as is a scalable synthesis required for accurate immunological, including vaccination, studies. Herein, we report an efficient, convergent, gram-scale synthesis of four stereo-isomers of a mycolic acid and its glucose ester. Binding to the antigen presenting protein CD1b and T cell activation studies are used to confirm the antigenicity of the synthetic material. The absolute stereochemistry of the syn-methoxy methyl moiety in natural material is evaluated by comparing its optical rotation with that of synthetic material.
Synergistic Relay Reactions To Achieve Redox-Neutral α-Alkylations of Olefinic Alcohols with Ruthenium(II) Catalysis
Kan, Jian,Li, Chao-Jun,Li, Chen-Chen,Li, Jianbin,Lv, Leiyang,Qiu, Zihang
supporting information, p. 4544 - 4549 (2020/02/04)
Herein, we report a ruthenium-catalyzed redox-neutral α-alkylation of unsaturated alcohols based on a synergistic relay process involving olefin isomerization (chain walking) and umpolung hydrazone addition, which takes advantage of the interaction between the two rather inefficient individual reaction steps to enable an efficient overall process. This transformation shows the compatibility of hydrazone-type “carbanions” and active protons in a one-pot reaction, and at the same time achieves the first Grignard-type nucleophilic addition using olefinic alcohols as latent carbonyl groups, providing a higher yield of the corresponding secondary alcohol than the classical hydrazone addition to aldehydes does. A broad scope of unsaturated alcohols and hydrazones, including some complex structures, can be successfully employed in this reaction, which shows the versatility of this approach and its suitability as an alternative, efficient means for the generation of secondary and tertiary alcohols.
Stereoselective synthesis and antiproliferative activity of the isomeric sphinganine analogues
?onková, Miroslava,Martinková, Miroslava,Gonda, Jozef,Jacková, Dominika,Pilátová, Martina Bago,Kupka, Daniel,Jáger, Dávid
, p. 76 - 85 (2018/12/11)
A flexible synthetic approach to biologically active sphingoid base-like compounds with a 3-amino-1,2-diol framework was achieved through a [3,3]-sigmatropic rearrangement and late stage olefin cross-metathesis as the key transformations. The stereochemistry of the newly created stereogenic centre was assigned via a single crystal X-ray analysis of the (4S,5R)-5-(hydroxymethyl)-4-vinyloxazolidine-2-thione. In order to rationalise the observed stereoselectivity of the aza-Claisen rearrangement, DFT calculations were carried out. The targeted isomeric sphingoid bases were screened in vitro for anticancer activity on a panel of seven human malignant cell lines. Cell viability experiments revealed that C17-homologues are more active than their C12 congeners.
Stereocontrolled Synthesis of Tetrafluoropentanols: Multivicinal Fluorinated Alkane Units for Drug Discovery
Bentler, Patrick,Erdeljac, Nathalie,Bussmann, Kathrin,Ahlqvist, Marie,Knerr, Laurent,Bergander, Klaus,Daniliuc, Constantin G.,Gilmour, Ryan
supporting information, p. 7741 - 7745 (2019/09/03)
A stereodivergent synthesis of four diastereomeric 2,3,4,5-tetrafluoropentanols is disclosed. X-ray crystallographic analysis reveals conformations that manifest sequential stereoelectronic gauche effects (σC-H/C → σC-F*), thereby generating topological diversity via subtle C(sp3)-H to C(sp3)-F exchange. Two representative tetrafluoro arrays have been incorporated into truncated analogues of Gilenya for the management of relapsing remitting multiple sclerosis. These closely similar multivicinal fluoroalkanes have notably different physicochemical profiles and were found to be stable in the presence of human microsomes.
Assignment of the relative and absolute stereochemistry of two novel epoxides using NMR and DFT-GIAO calculations
Moraes,Alvarenga,Demuner,Viana
, p. 109 - 115 (2018/05/03)
Considering the potential biological application of isobenzofuranones, especially as agrochemical defensives, two novel epoxides, (1aR,2R,2aR,5S,5aS,6S,6aS)-5-(hydroxymethyl)hexahydro-2,6-methanooxireno[2,3-f]isobenzofuran-3(1aH)-one (9), and (1aS,2S,2aR,5S,5aS,6R,6aR)-5-(hydroxymethyl)hexahydro-2,6-methanooxireno[2,3-f]isobenzofuran-3(1aH)-one (10), were synthesized from the readily available D-mannitol in six steps. The multiplicities of the hydrogens located at the bridge of the bicycle are distinct for epoxides 9 and 10 due to W coupling, and this feature was employed to confirm the assignment of these nuclei. Besides analyses of the 2D NMR spectra, the assignments of the nuclei at the epoxide ring were also inferred from information obtained by theoretical calculations. The calculated 1H and 13C NMR chemical shifts for eight candidate structures were compared with the experimental chemical shifts of 9 and 10 by measuring the mean absolute errors (MAE) and by the DP4 statistical analysis. The structures and relative configurations of 9, and 10 were determined via NMR spectroscopy assisted with theoretical calculations. As consequence of the enantioselective syntheses starting from a natural polyol, the absolute configurations of the epoxides 9 and 10 were also defined.
PROCESSES FOR PREPARING 2-DIHALO RIBOLACTONES
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Page/Page column 83; 84; 92; 93, (2017/06/21)
Methods for forming 2-bromo, 2-fluoro ribofuranose intermediates and 2-chloro, 2- fluoro ribofuranose intermediates for use in preparing antiviral nucleosides are disclosed. Methods for forming nucleosides, and nucleoside prodrugs, using the intermediates, are also disclosed. The methods all produce intermediates, and the resulting nucleosides and prodrugs thereof, wherein the chirality of the carbon at the 2-position is controlled. In some embodiments, the chemistry involves using chiral auxiliaries, such as (R)-2,2-dimethyl-l,3- dioxolane-4-carbaldehyde, and in other embodiments, the chemistry involves using chiral starting materials, such as D-xylose.
Stereoselective formal synthesis of (-)-fumagillol
Raghavan, Sadagopan,Yelleni, Mahesh Kumar Rao
, p. 4371 - 4379 (2017/07/03)
A formal synthesis of fumagillol, a congener of fumagillin that possesses varied biological activity, is disclosed. Initial attempts at preparing an allylic sulfide via an α-chloro sulfide met with failure. The successful route involves a carbonyl-ene reaction, one-pot stannyl cupration, methylation of resulting alkenyl copper and further Stille-coupling of the alkenyl stannane as the key steps.
PROCESS FOR THE PREPARATION OF [(1 S,2R)-3-[[(4-AMINOPHENYL)SULFONYL] (2-METHYLPROPYL)AMINO]-2-HYDROXY-1 -(PHENYLMETHYL)PROPYL]-CARBAMIC ACID (3R,3AS,6AR)HEXAHYDRO FURO[2,3-B]FURAN-3-YL ESTER AND ITS AMORPHOUS FORM
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, (2017/04/21)
The present invention relates to an improved process for the preparation of [(1 S,2R)-3-[ [(4-aminophenyl)sulfonyl] (2-methylpropyl)amino]-2-hydroxy- 1 -(phenylmethyl)propyl] - carbamic acid (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl ester compound of formula- 1 represented by the following structural formula:
