73346-74-4Relevant academic research and scientific papers
Combination of chemotherapy and oxidative stress to enhance cancer cell apoptosis
Fang, Jianguo,Hou, Yanan,Li, Jin,Li, Xinming,Wang, Song,Zhao, Jintao
, p. 3215 - 3222 (2020/04/08)
Cancer cells are vulnerable to reactive oxygen species (ROS) due to their abnormal redox environment. Accordingly, combination of chemotherapy and oxidative stress has gained increasing interest for the treatment of cancer. We report a novel seleno-prodrug of gemcitabine (Gem), Se-Gem, and evaluated its activation and biological effects in cancer cells. Se-Gem was prepared by introducing a 1,2-diselenolane (a five-membered cyclic diselenide) moiety into the parent drug Gemvia a carbamate linker. Se-Gem is preferably activated by glutathione (GSH) and displays a remarkably higher potency than Gem (up to a 6-fold increase) to a panel of cancer cell lines. The activation of Se-Gem by GSH releases Gem and a seleno-intermediate nearly quantitatively. Unlike the most ignored side products in prodrug activation, the seleno-intermediate further catalyzes a conversion of GSH and oxygen to GSSG (oxidized GSH) and ROS via redox cycling reactions. Thus Se-Gem may be considered as a suicide agent to deplete GSH and works by a combination of chemotherapy and oxidative stress. This is the first case that employs a cyclic diselenide in prodrug design, and the success of Se-Gem as well as its well-defined action mechanism demonstrates that the 1,2-diselenolane moiety may serve as a general scaffold to advance constructing novel therapeutic molecules with improved potency via a combination of chemotherapy and oxidative stress.
Novel protection of 1,2-diol for trans-dihydroxycyclopentene ring construction by the C[sbnd]H insertion of alkylidene carbene: Formal total synthesis of (+)-trehazolin
Ohira, Susumu,Kuboki, Atsuhito,Takimoto, Yoshimi,Matsuda, Kyosuke,Itasaki, Saori,Urushibata, Yuki,Takano, Yoshiyuki,Nakamura, Yuuki
, (2019/09/03)
The chiral vicinal diol was protected as 6-methylene-1,4-dioxepane to construct a cyclopentene ring by the C[sbnd]H insertion of alkylidene carbene. The removal of the protecting group was achieved in a few steps, affording the corresponding diol in a reasonable yield. Using these reactions, the known synthetic intermediate for (+)-trehazolin was synthesized from D-diethyl tartrate. In addition, a short route to the intermediate from a D-mannitol derivative was described.
Supramolecular gels from sugar-linked triazole amphiphiles for drug entrapment and release for topical application
Sharma, Komal,Joseph, Jojo P.,Sahu, Adarsh,Yadav, Narender,Tyagi, Mohit,Singh, Ashmeet,Pal, Asish,Kartha, K.P. Ravindranathan
, p. 19819 - 19827 (2019/07/05)
A simple molecular framework obtained by cross-linking a hydrophobic chain with S,S- and R,R-tetritol by the copper-catalysed azide-alkyne cycloaddition reaction is found to serve as an excellent bioisostere for self-assembly. The hexadecyl-linked triazolyl tetritol composite spontaneously self-assembles in n-hepane and methanol to form hierarchical organogels. Microscopic analyses and X-ray diffraction studies demonstrate eventual formation of nanotubes through lamellar assembly of the amphiphiles. A rheological investigation shows solvent-dictated mechanical properties that obey power law behavior similar to other low molecular weight gelators (LMOGs). The gel network was then utilized for the entrapment of drugs e.g. ibuprofen and 5-fluorouracil, with tunable mechanical behaviour under applied stress. The differential release profiles of the drugs over a period of a few hours as a result of the relative spatio-temporal location in the supramolecular network can be utilized for topical formulations.
Stereoselective synthesis of the lichen metabolite, (+) montagnetol and its congeners as antimicrobial agents
Mallavadhani, Uppuluri Venkata,Boddu, Ramakrishna,Rathod, Balaji B.,Reddy Setty, Prakasam
supporting information, p. 2992 - 2999 (2018/10/15)
In view of structural diversity, (+) montagnetol, the major metabolite of the fruticose lichen, Roccella montagnei was synthesized along with three of its congeners by employing highly efficient protocols. (+) Montagnetol (2 R, 3S; 11) and (-) montagnetol (2S, 3R; 5) were synthesized in 7 and 9 steps, respectively, from L-ascorbic acid. The two new congeners 3 (2 R, 3R) and 6 (2S, 3S), which differ in configuration at C-2 and C-3 positions of the (+) montagnetol, were synthesized from (?) diethyl D-tartrate and (+) diethyl L-tartrate, respectively. The synthesized compounds were evaluated in vitro for antimicrobial activity against two Gram-positive (S. aureus and E. coli) and two Gram-negative (S. typhi and P. aeruginosa) bacteria and one fungal strain Candida albicans. Interestingly, the congener 3 showed promising anti-bacterial activity (MIC: 0.062 μg/ml) against P. aeruginosa, whereas the congener 6 displayed potent anti-fungal activity (MIC: 0.062 μg/ml) against C. Albicans.
CYCLIC COMPOUND
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Paragraph 0320, (2018/04/13)
The present invention provides compounds having a Toll-like receptor 4 (TLR4) signaling inhibitory action useful as preventive and therapeutic drugs of autoimmune disease and/or inflammatory disease or diseases such as chemotherapy-induced peripheral neuropathy (CIPN), chemotherapy-induced neuropathic pain (CINP), liver injury, ischemia-reperfusion injury (IRI) and the like. The present invention relates to a compound represented by formula (I) and a salt thereof: (wherein, each symbol is explained in greater detail in the specification).
Stereocontrolled synthesis of four isomeric linoleate triols of relevance to skin barrier formation and function
Davis, Robert W.,Allweil, Alexander,Tian, Jianhua,Brash, Alan R.,Sulikowski, Gary A.
, p. 4571 - 4573 (2018/11/23)
Linoleate triol esters are intermediates along the pathway of formation of the mammalian skin permeability barrier. In connection with the study of their involvement in barrier formation we required access to isomerically pure and defined samples of four linoleate triol esters. A common synthetic strategy was developed starting from isomeric alkynols derived from D-tartaric acid and 2-deoxy-D-ribose.
Chiroptical properties of 2,2’-bioxirane
Daugey,De Rycke,Brotin,Buffeteau
supporting information, p. 342 - 350 (2018/01/15)
The two enantiomers of 2,2′-bioxirane were synthesized, and their chiroptical properties were thoroughly investigated in various solvents by polarimetry, vibrational circular dichroism (VCD), and Raman optical activity (ROA). Density functional theory (DFT) calculations at the B3LYP/aug-cc-pVTZ level revealed the presence of three conformers (G+, G?, and cis) with Gibbs populations of 51, 44, and 5% for the isolated molecule, respectively. The population ratios of the two main conformers were modified for solvents exhibiting higher dielectric constants (G? form decreases whereas G+ form increases). The behavior of the specific optical rotation values with the different solvents was correctly reproduced by time-dependent DFT calculations using the polarizable continuum model (PCM), except for the benzene for which explicit solvent model should be necessary. Finally, VCD and ROA spectra were perfectly reproduced by the DFT/PCM calculations for the Boltzmann-averaged G+ and G? conformers.
Hydrogen Bonding-Assisted Enhancement of the Reaction Rate and Selectivity in the Kinetic Resolution of d,l-1,2-Diols with Chiral Nucleophilic Catalysts
Fujii, Kazuki,Mitsudo, Koichi,Mandai, Hiroki,Suga, Seiji
supporting information, p. 2778 - 2788 (2017/08/23)
An extremely efficient acylative kinetic resolution of d,l-1,2-diols in the presence of only 0.5 mol% of binaphthyl-based chiral N,N-4-dimethylaminopyridine was developed (selectivity factor of up to 180). Several key experiments revealed that hydrogen bonding between the tert-alcohol unit(s) of the catalyst and the 1,2-diol unit of the substrate is critical for accelerating the rate of monoacylation and achieving high enantioselectivity. This catalytic system can be applied to a wide range of substrates involving racemic acyclic and cyclic 1,2-diols with high selectivity factors. The kinetic resolution of d,l-hydrobenzoin and trans-1,2-cyclohexanediol on a multigram scale (10 g) also proceeded with high selectivity and under moderate reaction conditions: (i) very low catalyst loading (0.1 mol%); (ii) an easily achievable low reaction temperature (0 °C); (iii) high substrate concentration (1.0 M); and (iv) short reaction time (30 min). (Figure presented.).
Formal Total Synthesis of Amphidinolide e
Bosch, Lluís,Mola, Laura,Petit, Elena,Saladrigas, Mar,Esteban, Jorge,Costa, Anna M.,Vilarrasa, Jaume
, p. 11021 - 11034 (2017/10/27)
A formal total synthesis of the cytotoxic macrolide amphidinolide E is reported. The strategic steps are three Julia-Kocienski reactions (J-K), for the formation of the C5-C6, C9-C10, and C17-C18 double bonds, a Suzuki-Molander C21-C22 bond formation reaction, and a Kita-Trost macrolactonization. The "instability" of the two dienic systems and of the stereocenter at C2 (allylic methine, α to the carboxy group) and the protecting groups at C17-OH and C18-OH have posed difficult challenges. Each Julia-Kocienski olefination has been systematically optimized to provide the highest possible E/Z ratios.
Stereoselective Synthesis of the C27-C35 Eribulin Fragment and Its Utilization in Building Structurally Diverse Macrocycles
Konda, Saidulu,Khatravath, Mahender,Mallurwar, Naveen Kumar,Rao, Pallavi,Sripelly, Shivashankar,Iqbal, Javed,Arya, Prabhat
, p. 1663 - 1683 (2016/05/24)
A practical and scalable stereoselective synthesis of the western substituted tetrahydrofuran ring C27-C35 fragment of eribulin was developed by using (2S,3S)-tartaric acid as a cheap starting material that was converted into an intermediate through a stereoselective vinylation and cross-metathesis as the key steps. A regio-and stero-selective intramolecular oxy-Michael cyclization or an iodocyclization reaction finally provided the required western tetrahydrofuran ring fragment and its related isomeric analogues. These key fragments were further utilized in obtaining several types of macrocyclic derivatives for exploration of their biological properties. The simplicity of our present approach has the potential to be considered for large-scale syntheses of key fragments of eribulin and related analogues.
