127903-20-2Relevant articles and documents
A facile synthesis of ω-aminoalkyl ammonium hydrogen phosphates
Kong, Wei Bo,Zhou, Xiao Yong,Yang, Yang,Xie, Xing Yi
, p. 923 - 926 (2012)
A series of ω-aminoalkyl ammonium hydrogen phosphates were synthesized through a simple and efficient three-step method. The starting materials, ω-aminoalkyl alcohols (AC-n, with carbon number n = 3, 4, 5, 6), were amino-protected with 9-fluorenylmethyl chloroformate (Fmoc-Cl), followed by phosphorylation with POCl3 and deprotection in piperidine/DMF. The structures of each intermediate and final product were confirmed by 1H NMR, FTIR and mass spectrum. The yield of each step was about 77-92%, with a total yield higher than 56%. This new method was superior in low-cost raw materials, mild reaction temperatures (0-25°C) and easy purification methods.
Amphotericin B covalent dimers forming sterol-dependent ion-permeable membrane channels
Matsumori, Nobuaki,Yamaji, Nahoko,Matsuoka, Shigeru,Oishi, Tohru,Murata, Michio
, p. 4180 - 4181 (2002)
Polyenemacrolides such as amphotericin B (AmB) were thought to assemble together and form an ion channel across plasma membranes. Their antimicrobial activity has been accounted for by this assemblage, whose stability and activity are dependent on sterol constituents of lipid bilayer membranes. The structure of this channel-like assemblage formed in biomembranes has been a target of extensive investigations for a long time. For the first step to this goal, we prepared several AmB dimers with various linkers and tested for their channel-forming activity. Among these, AmB dimers that bore an aminoalkyl-dicarboxylate tether covalently linked between amino groups of AmB showed potent hemolytic activity. Furthermore, K+ influx actions monitored by measuring the pH of the liposome lumen by 31P NMR revealed that the dimers formed the molecular assemblage similar to that of AmB in phospholipid membrane. Judging from changes in 31P NMR spectra, the dimers appeared to induce "all-or-none"-type ion flux across the liposome membrane in the presence of ergosterol, which suggested that the ion channel formed by ergosterol/dimer is similar to that of AmB. With these data in hand, we are now trying to elucidate the structure of the ion-channel complex by making the labeled conjugates of AmB for NMR measurements. Copyright
Preparation method of triphosphate compound and deoxynucleotide
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Paragraph 0055-0057; 0125, (2020/11/23)
The invention discloses a preparation method of a triphosphate compound and deoxynucleotide. In the preparation method of the triphosphate compound, tetrahydrofuran is used for replacing trimethyl phosphate/triethyl phosphate, tri-n-propylamine is used for replacing tri-n-butylamine, and acetonitrile is used for replacing N,N-dimethylformamide; so that the preparation method has the advantages that the yield is high, few byproducts are produced, a solvent is easy to remove, and the triphosphate compound is non-toxic, safe and the like. According to the preparation method of the deoxynucleotide, the morpholine dimethylformamide solution is used for replacing a triethylamine solution to remove the F-moc group, so that the reaction time is greatly shortened, the generation of byproducts is reduced, and the yield is improved.
Structure-Permeability Relationship of Semipeptidic Macrocycles - Understanding and Optimizing Passive Permeability and Efflux Ratio
Le Roux, Antoine,Blaise, émilie,Boudreault, Pierre-Luc,Comeau, Christian,Doucet, Annie,Giarrusso, Marilena,Collin, Marie-Pierre,Neubauer, Thomas,K?lling, Florian,G?ller, Andreas H.,Seep, Lea,Tshitenge, Dieudonné T.,Wittwer, Matthias,Kullmann, Maximilian,Hillisch, Alexander,Mittendorf, Joachim,Marsault, Eric
supporting information, p. 6774 - 6783 (2020/07/28)
We herein report the first thorough analysis of the structure-permeability relationship of semipeptidic macrocycles. In total, 47 macrocycles were synthesized using a hybrid solid-phase/solution strategy, and then their passive and cellular permeability was assessed using the parallel artificial membrane permeability assay (PAMPA) and Caco-2 assay, respectively. The results indicate that semipeptidic macrocycles generally possess high passive permeability based on the PAMPA, yet their cellular permeability is governed by efflux, as reported in the Caco-2 assay. Structural variations led to tractable structure-permeability and structure-efflux relationships, wherein the linker length, stereoinversion, N-methylation, and peptoids site-specifically impact the permeability and efflux. Extensive nuclear magnetic resonance, molecular dynamics, and ensemble-based three-dimensional polar surface area (3D-PSA) studies showed that ensemble-based 3D-PSA is a good predictor of passive permeability.
Extracellular targeted drug conjugates
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Page/Page column 90-92, (2016/09/26)
The present invention relates to, inter alia, extracellular drug conjugates (EDC) in which an antibody or other targeting agent (e.g. a targeting moiety) is linked to a drug through a linker (e.g. a non-cleavable linker). These conjugates are useful in the treatment of disease and/or as a tool in the evaluation of biological systems.
Photoredox removal of p-methoxybenzyl ether protecting group with hydrogen peroxide as terminal oxidant
Liu, Zheng,Zhang, Yi,Cai, Zheren,Sun, Hao,Cheng, Xu
, p. 589 - 593 (2015/03/05)
We report a mild protocol for removal of the p-methoxybenzyl ether protecting group under acidic conditions with eosin Y combined with LEDs as a photoredox catalysis system and hydrogen peroxide as the terminal oxidant. This protocol is compatible with ethers derived from primary, secondary, and tertiary alcohols, as well as with various functional groups. The protocol showed unusual selectivity for a tertiary ether over a primary ether. The scale up to gram scale is also explored and identical reactivity is observed.
Elucidation of the active conformation of vancomycin dimers with antibacterial activity against vancomycin-resistant bacteria
Nakamura, Jun,Yamashiro, Hidenori,Hayashi, Sayaka,Yamamoto, Mami,Miura, Kenji,Xu, Shu,Doi, Takayuki,Maki, Hideki,Yoshida, Osamu,Arimoto, Hirokazu
supporting information, p. 12681 - 12689 (2012/11/07)
Covalently linked vancomycin dimers have attracted a great deal of attention among researchers because of their enhanced antibacterial activity against vancomycin-resistant strains. However, the lack of a clear insight into the mechanisms of action of these dimers hampers rational optimization of their antibacterial potency. Here, we describe the synthesis and antibacterial activity of novel vancomycin dimers with a constrained molecular conformation achieved by two tethers between vancomycin units. Conformational restriction is a useful strategy for studying the relationship between the molecular topology and biological activity of compounds. In this study, two vancomycin units were linked at three distinct positions of the glycopeptide (vancosamine residue (V), C terminus (C), and N terminus (N)) to form two types of novel vancomycin cyclic dimers. Active NC-VV-linked dimers with a stable conformation as indicated by molecular mechanics calculations selectively suppressed the peptidoglycan polymerization reaction of vancomycin-resistant Staphylococcus aureus in vitro. In addition, double-disk diffusion tests indicated that the antibacterial activity of these dimers against vancomycin-resistant enterococci might arise from the inhibition of enzymes responsible for peptidoglycan polymerization. These findings provide a new insight into the biological targets of vancomycin dimers and the conformational requirements for efficient antibacterial activity against vancomycin-resistant strains. Squashing superbugs: Conformationally constrained vancomycin dimers that inhibit the peptidoglycan synthesis of vancomycin-resistant bacteria were prepared (see scheme). The potent antibacterial activity of the dimers was suggested to arise from their direct action on transglycosylase enzymes. Copyright
Oxidative photoredox catalysis: Mild and selective deprotection of PMB ethers mediated by visible light
Tucker, Joseph W.,Narayanam, Jagan M. R.,Shah, Pinkey S.,Stephenson, Corey R. J.
, p. 5040 - 5042 (2011/06/10)
Herein we report an advancement in the application of visible light photoredox catalysts in the oxidation of electron-rich arenes resulting in the selective deprotection of para-methoxybenzyl (PMB) ethers. This method is highlighted by excellent functional group tolerance, protecting group orthogonality, mild reaction conditions and avoidance of stoichiometric redox byproducts.
A versatile annulation protocol toward novel constrained phosphinic peptidomimetics
Nasopoulou, Magdalini,Georgiadis, Dimitris,Matziari, Magdalini,Dive, Vincent,Yiotakis, Athanasios
, p. 7222 - 7228 (2008/02/12)
(Chemical Equation Presented) The development of a novel 3-center 2-component annulation reaction between α,ω-carbamoylaldehydes and suitably monoalkylated phosphinic acids is reported. Depending on the starting α,ω-carbamoylaldehyde, diverse phosphinic scaffolds varying in the size of their rigidity element, the nature and stereochemistry of substituents, and the participation of heteroatoms in the azacyclic ring system can be obtained in one synthetic step and in high yield. In addition, this methodology allows the synthesis of Fmoc-protected constrained aminophosphinic acids that can be easily converted to suitable pseudodipeptide building blocks compatible with the requirements of peptide synthesis on the solid phase. Finally, the careful choice of both substituents and protecting groups can provide functionally diverse, orthogonally protected constrained scaffolds for extended derivatization of the target phosphinic peptidomimetic structrures.
Design and synthesis of indole-based peptoids as potent noncompetitive antagonists of transient receptor potential vanilloid 1
Quintanar-Audelo, Martina,Fernández-Carvajal, Asia,Van Den Nest, Wim,Carre?o, Cristina,Ferrer-Montiel, Antonio,Albericio, Fernando
, p. 6133 - 6143 (2008/09/16)
The vanilloid receptor subunit 1, or transient receptor potential vanilloid 1 (TRPV1), integrates physical and chemical stimuli in the peripheral nervous system, playing a key role in inflammatory pain. Identification of potent TRPV1 antagonists is thus an important goal of current neuropharmacology. Herein, we describe the solid-phase synthesis of a series of indole-based peptoids (N-alkylglycines) and the biological activity of the peptoids as novel TRPV1 antagonists. The potency and selectivity of the compounds were determined by electrophysiological recordings in Xenopus oocytes. The most potent and selective noncompetitive TRPV1 antagonist of the series, compound 7, represents an interesting pharmacophoric structure for analgesic lead optimization.
