- 4-(4,6-dimethoxy[1,3,5]triazin-2-yl)-4-methyl-morpholinium chloride (DMTMM): A valuable alternative to PyBOP for solid phase peptide synthesis
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The salt formed from 2-chloro-4,6-dimethoxy[1,3,5]triazine and N- methylmorpholine (DMTMM) is an effective coupling agent for solid phase peptide synthesis that can be used as economical alternative to PyBOP. Several oligopeptides were prepared on a Wang type resin using this reagent and the yields and purity of the products were always comparable with those obtained with PyBOP as the coupling agent.
- Falchi, Alessandro,Giacomelli, Giampaolo,Porcheddu, Andrea,Taddei, Maurizio
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Read Online
- Synthesis and Properties of Functional Glycomimetics through Click Grafting of Fucose onto Chondroitin Sulfates
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Fucosylated chondroitin sulfate (fCS), a representative marine polysaccharide isolated from sea cucumber, possesses diverse biological functions especially as a promising anticoagulant. However, its supply suffers from the challenges of high-cost materials, different species, and batch-to-batch variability. In the present study, we designed a concise route for the synthesis of functional glycomimetics by natural fCS as a template. 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride-mediated amidation was applied on chondroitin sulfates for site-selective alkynylation with controllable ratios between 0.15 and 0.78. A small library of 12 fCS glycomimetics with specific sulfation patterns and fucose branches was prepared through copper-catalyzed azide-alkyne cycloaddition, which was fully characterized by nuclear magnetic resonance spectroscopy and size-exclusion chromatography with multiangle light scattering and refractive index. Through screening of their biological activities, CSE-F1 and CSE-SF1 exhibited anticoagulant activities through intrinsic pathway and inhibition of factor Xa by antithrombin III. The concise approach developed herein supplies novel glycopolymers to mimic the distinct functions of natural polysaccharides and promote the development of marine carbohydrate-based drugs.
- Fan, Fei,Zhang, Ping,Wang, Lihao,Sun, Tiantian,Cai, Chao,Yu, Guangli
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Read Online
- Kinetically driven intra-and interchain association of hydrophobically and hydrophilically modified poly(acrylic acid) in dilute aqueous solutions
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Effects of pH, dodecyl, and PEO contents as well as the method of preparing the solution on the formation of the unimolecular micelles (unimer micelle) or aggregates made of poly(acrylic acid)-graftpoly( ethylene oxide)-graft-dodecyl (PAA-g-PEO-g-dodecyl) and PAA-g-dodecyl have been studied by a combination of static and dynamic laser light scattering (SLS and DLS). It revealed that: in most cases, these copolymers tend to form interchain associates; while low pH value, proper high dodecyl content and fast switch rate of solvent quality promote intrachain association. These phenomena of the system being trapped in a metastable state can be mainly attributed to its kinetic pathway: the factors mentioned earlier can enhance the initial intrachain contraction, leading to τc (interaction time) e (entanglement time) for the two interaction intrachain globules. So they behave like tiny "elastic balls" and their further merge/fusion become nearly impossible during their interaction time (τc). In this way, the copolymer system is trapped in the metastable, unimer micelle state. The interplay of τc and τe in the formation of metastable unimer micelles or stable aggregates has been discussed in detail.
- Hao, Jinkun,Li, Zhiyong,Cheng, He,Wu, Chi,Han, Charles C.
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Read Online
- Bifunctional copper(II) chelators from the coupling of the encapsulating ligand 1-methyl-8-amino-3,13,16-trithia-6,10,19-triazabicyclo[6.6.6]icosane (AMN3S3sar) with carboxylic acids; Applications of the coupling agent DMT-MM
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Reaction of 1-methyl-8-amino-3,13,16-trithia-6,10,19-triazabicyclo[6.6.6]icosane (AMN3S3sar) with the amide coupling agent 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) and 4-nitrobenzoic acid, the protected amine 4-(1,3-dioxoisoindolin-2-yl)benzoic acid and the tricarboxylic acid, benzene-1,3,5-tricarboxylic acid (trimesic acid) resulted in the three new ligands N3S3amideSarArNO2, N3S3amideSarAr, and (AMN3S3sar)3TMA. Two of the respective copper(II) complexes have been isolated and characterized.
- Lee, Hui Hui,Lim, Peiying Alinia,Vu, Hoan,Poulsen, Sally-Ann,Gahan, Lawrence R.
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Read Online
- Synthesis and Antimicrobial Evaluation of Bis-morpholine Triazine Quaternary Ammonium Salts
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Efficient, environmentally and economically sustainable, and nontoxic antibacterial products are of global relevance in the fight against microorganism contamination. In this work, an easy and straightforward method for the synthesis of bis-morpholino triazine quaternary ammonium salts (bis-mTQAS) is reported, starting from 2,4,6-trichloro-1,3,5-triazine or 2,4-dichloro-6-methoxy-1,3,5-triazine and various N-alkylmorpholines. Bis-mTQAS were tested as antimicrobials against Gram-negative and Gram-positive bacterial strains. The best-performing bis-mTQAS were found to achieve total disinfection against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 at 50 and 400 μg/mL, respectively. Distinctively, bis-mTQAS with the highest antimicrobial efficiency had lowest cytotoxicity.
- Morandini, Andrea,Leonetti, Benedetta,Riello, Pietro,Sole, Roberto,Gatto, Vanessa,Caligiuri, Isabella,Rizzolio, Flavio,Beghetto, Valentina
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supporting information
p. 3172 - 3176
(2021/08/03)
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- Phosphorus-Based Organocatalysis for the Dehydrative Cyclization of N-(2-Hydroxyethyl)amides into 2-Oxazolines
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A metal-free, biomimetic catalytic protocol for the cyclization of N-(2-hydroxyethyl)amides to the corresponding 2-oxazolines (4,5-dihydrooxazoles), promoted by the 1,3,5,2,4,6-triazatriphosphorine (TAP)-derived organocatalyst tris(o-phenylenedioxy)cyclotriphosphazene (TAP-1) has been developed. This approach requires less precatalyst compared to the reported relevant systems, with respect to the phosphorus atom (the maximum turnover number (TON) ~30), and exhibits a broader substrate scope and higher functional-group tolerance, providing the functionalized 2-oxazolines with retention of the configuration at the C(4) stereogenic center of the 2-oxazolines. Widely accessible β-amino alcohols can be used in this approach, and the cyclization of N-(2-hydroxyethyl)amides provides the desired 2-oxazolines in up to 99% yield. The mechanism of the reaction was studied by monitoring the reaction using spectral and analytical methods, whereby an 18O-labeling experiment furnished valuable insights. The initial step involves a stoichiometric reaction between the substrate and TAP-1, which leads to the in situ generation of the catalyst, a catechol cyclic phosphate, as well as to a pyrocatechol phosphate and two possible active intermediates. The dehydrative cyclization was also successfully conducted on the gram scale.
- Foo, Siong Wan,Mori, Shogo,Ogawa, Saeko,Saito, Susumu,Soleymani Movahed, Farzaneh
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- Site-Selective Modification of Peptides and Proteins via Interception of Free-Radical-Mediated Dechalcogenation
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The development of site-selective chemistry targeting the canonical amino acids enables the controlled installation of desired functionalities into native peptides and proteins. Such techniques facilitate the development of polypeptide conjugates to advance therapeutics, diagnostics, and fundamental science. We report a versatile and selective method to functionalize peptides and proteins through free-radical-mediated dechalcogenation. By exploiting phosphine-induced homolysis of the C?Se and C?S bonds of selenocysteine and cysteine, respectively, we demonstrate the site-selective installation of groups appended to a persistent radical trap. The reaction is rapid, operationally simple, and chemoselective. The resulting aminooxy linker is stable under a variety of conditions and selectively cleavable in the presence of a low-oxidation-state transition metal. We have explored the full scope of this reaction using complex peptide systems and a recombinantly expressed protein.
- Griffiths, Rhys C.,Smith, Frances R.,Long, Jed E.,Williams, Huw E. L.,Layfield, Robert,Mitchell, Nicholas J.
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supporting information
p. 23659 - 23667
(2020/10/21)
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- POLYPEPT(O)ID-BASED GRAFT COPOLYMERS FOR IN VIVO IMAGING BY TETRAZINE TRANSCYCLOOCTENE CLICK CHEMISTRY
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There is provided novel polypeptide-based carrier systems, which make it possible to label polymeric nanoparticles in the living organism. This enables new approaches in tumor diagnostics (high signal to background ratio) and radiotherapy (radiotherapy of solid tumors). The polypeptide-based carrier system comprises a polypept(o)idic comb (graft) copolymer, and one or more tetrazine bioorthogonal functional groups each linked to a diagnostic agent.
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Page/Page column 11
(2020/01/24)
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- Heparin alendronate sodium conjugate synthetic method and drugs
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The invention relates to a heparin alendronate sodium conjugate synthetic method and drugs in the field of medicine. The heparin alendronate sodium conjugate synthetic method comprises the steps: step1, firstly, dissolving 2-chloro-4,6-dimethoxy-1,3,5-triazine in tetrahydrofuran, adding 4-methylmorpholine, stirring for 1-2 h at room temperature, collecting by filtration and washing a precipitatefive times with THF, and thus then obtaining a DMT-MM condensation agent after 48 h of vacuum drying; and step 2, adding heparin and the condensation agent into ultra-pure water, stirring for 1 h, then adding an alendronate sodium solution into the mixed solution of heparin and the condensation agent, carrying out reaction for 24-48 h, pouring the solution into a dialysis bag, dialysing for 48-72h, changing water once every 4 h, finally, freeze-drying the product obtained from dialysis, and thus obtaining the heparin alendronate sodium conjugate drugs. In the method, alendronate sodium is modified by heparin, so the solubility of the drugs is increased, the bioavailability is improved, the cytotoxicity is reduced and the formation of osteoclasts is effectively inhibited.
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Paragraph 0009; 0030-0032
(2019/10/01)
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- Indole and quinoline derivatives and its preparation method and application
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The invention provides an indoloquinoline derivative, a preparation method and application thereof in preparing antitumor drugs and antiviral drugs. The chemical structure of the indoloquinoline derivative is shown as a formula I. Experiments show that a partly-boric-acid-modified indoloquinoline derivative and a non-boric-acid-modified indoloquinoline derivative have strong inhibition effect on various tumor cell strains, thereby being capable of being used for preparation of the antitumor drugs, and have strong antiviral activity, thereby being capable of being used for preparation of the antiviral drugs.
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Paragraph 0112; 0114
(2017/02/28)
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- An easy and convenient synthesis of β-lactams via a one-pot staudinger reaction with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride starting from substituted carboxylic acids
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An easy and convenient direct synthesis of 2-azetidinones is described. The [2+2] cycloaddition reaction of imines and carboxylic acids using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) has been employed to synthesize a variety of 2-azetidinones in high yields. The products were easily isolated because the byproducts are highly soluble in water.
- Zarei, Maaroof
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- Bifunctional copper(II) chelators from the coupling of the encapsulating ligand 1-methyl-8-amino-3,13,16-trithia-6,10,19-triazabicyclo[6.6.6]icosane (AMN3S3sar) with carboxylic acids; Applications of the coupling agent DMT-MM
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Reaction of 1-methyl-8-amino-3,13,16-trithia-6,10,19-triazabicyclo[6.6.6]icosane (AMN3S3sar) with the amide coupling agent 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) and 4-nitrobenzoic acid, the protected amine 4-(1,3-dioxoisoindolin-2-yl)benzoic acid and the tricarboxylic acid, benzene-1,3,5-tricarboxylic acid (trimesic acid) resulted in the three new ligands N3S3amideSarArNO2, N3S3amideSarAr, and (AMN3S3sar)3TMA. Two of the respective copper(II) complexes have been isolated and characterized.
- Lee, Hui Hui,Lim, Peiying Alinia,Vu, Hoan,Poulsen, Sally-Ann,Gahan, Lawrence R.
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p. 627 - 634
(2015/02/19)
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- PROCESSES FOR PREPARING ANTIVIRAL COMPOUNDS
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The present disclosure provides processes for the preparation of a compound of formula: which is useful as an antiviral agent. The disclosure also provides compounds that are synthetic intermediates.
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Paragraph 0600-0601
(2015/12/30)
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- Folate-appended β-cyclodextrin as a promising tumor targeting carrier for antitumor drugs in vitro and in vivo
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A large number of antitumor drug delivery carriers based on passive targeting and/or active targeting have been developed. However, encapsulation of antitumor drugs into these drug carriers is often complicated, and antitumor activities of these targeting systems are not satisfactory. In the present study, we first prepared heptakis-6-folic acid (FA)-appended β-cyclodextrin (β-CyD) possessing two caproic acids between FA and a β-CyD molecule as a spacer (Fol-c2-β-CyD) and evaluated the potential as a novel tumor targeting carrier for antitumor drugs through a complexation. Fol-c2-β-CyD formed an inclusion complex with doxorubicin (DOX) at a 1:1 molar ratio with a markedly high stability constant (>106 M-1). Cellular uptake of DOX was increased by the addition of Fol-c2-β-CyD in KB cells, a folate receptor-α (FR-α)-positive cell line. Additionally, Fol-c2-β-CyD increased in vitro antitumor activities of antitumor drugs such as DOX, vinblastine (VBL), and paclitaxel (PTX) in KB cells, but not in A549 cells, a FR-α-negative cell line. The complex of DOX with Fol-c2-β- CyD markedly increased antitumor activity of DOX, not only after intratumoral administration but also after intravenous administration to mice subcutaneously inoculated Colon-26 cells, a FR-α-positive cell line. These findings suggest that Fol-c2-β-CyD could be useful as a promising antitumor drug carrier.
- Okamatsu, Ayaka,Motoyama, Keiichi,Onodera, Risako,Higashi, Taishi,Koshigoe, Takahiro,Shimada, Yasutaka,Hattori, Kenjiro,Takeuchi, Tomoko,Arima, Hidetoshi
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p. 724 - 733
(2013/07/05)
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- Study on 1,3,5-triazine chemistry in dehydrocondensation: Gauche effect on the generation of active triazinylammonium species
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The reaction of 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) with various nitrogen-containing compounds, particularly tertiary amines (tert-amines), has been studied for the preparation of 2-(4,6-dimethoxy-1,3,5-triazinyl) trialkylammonium salts [DMT-Am(s)]. DMT-Ams derived from aliphatic tert-amines exhibited activity for the dehydrocondensation between a carboxylic acid and an amine to form an amide in a model reaction. Based on a conformational analysis of DMT-Ams and tert-amines by NMR and X-ray diffraction methods, we concluded that a β-alkyl group maintained in a gauche relationship with the nitrogen lone pair of tert-amines significantly hinders the approach of CDMT to the nitrogen. Thus, trimethylamine and quinuclidine without such alkyl groups readily react with CDMT whereas triethylamine, possessing two or three such gauche β-alkyl groups in the stable conformations, does not react at all. The theory of "gauche β-alkyl group effect" proposed here provides useful guidelines for the preparation of DMT-Ams possessing various tertiary amine moieties. An investigation of the dehydrocondensation activity of tert-amines in a CDMT/tert-amine system that involves in situ generation of DMT-Am, showed that the gauche effect of the β-alkyl group becomes quite pronounced; the yield of the amide decreases significantly with tert-amines possessing an unavoidable gauche β-alkyl group. Thus, the tert-amine/CDMT systems are useful for judging whether tert-amines can readily react with CDMT without isolation of DMT-Ams. The right approach! The structure-activity relationship of nitrogen-containing compounds including aliphatic tertiary amines in the reaction with 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) has been investigated (see scheme). The theory of "gauche β-alkyl group effect" proposed here provides useful guidelines for the preparation of triazine-based dehydrocondensation reagents (DMT-Ams) possessing various tertiary amine moieties. Copyright
- Kunishima, Munetaka,Ujigawa, Takae,Nagaoka, Yoshie,Kawachi, Chiho,Hioki, Kazuhito,Shiro, Motoo
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p. 15856 - 15867
(2013/01/16)
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- Synthesis and spectral characteristics of fluorescent dyes based on coumarin fluorophore and hindered amine stabilizer in solution and polymer matrices
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The spectral properties of novel bifunctional dyes based on - coumarin and diethylamino-coumarin and piperidine parent amine and N-oxyl and N-alkoxy derivatives were compared in cyclohexane, methanol, diethylene glycol, acetonitrile and chloroform solvents and in polystyrene, poly(methyl methacrylate) and poly(vinyl chloride) polymer matrices. The fluorescence of the derivatives excited at the longest-wavelength band around 295 nm is very low for coumarin-based dyes, whereas the fluorescence of the 7-diethylamino-3- carboxy coumarin dyes excited at 420 nm is as intense as that of anthracene in comparable conditions. Intramolecular quenching on the singlet level, monitored by fluorescence and expressed as the ratio of ΦNH/Φ NO for the parent amine and N-oxyl and ΦNOR/ ΦNO for N-alkyloxy and N-oxyl, is more efficient in polymer matrices than in solvents. The spectral properties of 7-diethylamino-3-carboxy coumarin fluorophores depend on the polarity and viscosity of the environment. Highest values of quantum yield ratio were observed for 7-diethylamino-3-carboxy coumarin dyes in polystyrene and poly(vinylchloride). Though the fluorescence intensity is higher in chloroform or in poly(vinyl chloride) matrices, the intramolecular quenching efficiency of a given fluorophore by nitroxide is higher in low polarity media, such as cyclohexane and polystyrene.
- Danko, Martin,Szabo, Erik,Hrdlovic, Pavol
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experimental part
p. 129 - 138
(2011/12/14)
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- The design, synthesis, and application of a chiral coupling reagent derived from strychnine for the enantioselective activation of a carboxylic group
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The concept of a chiral coupling reagent for the enantioselective synthesis of peptides with a predictable configuration and enantiomeric purity from racemic substrates is presented. The reagent was prepared by treatment of strychninium tetrafluoroborate with 2-chloro-4,6-dimethoxy-1,3,5-triazine in the presence of sodium bicarbonate yielding N-(4,6-dimethoxy-1,3,5-triazin-2-yl)strychninium tetrafluoroborate in high yield, which is stable at room temperature, and in a broad range of solvents gave enriched Z-Ala-Phe-OMe (dr from 95/5 to 60/40) in high yield with d-configuration on the alanine residue starting from rac-Z-Ala-OH.
- Kolesińska, Beata,Kasperowicz, Katarzyna,Sochacki, Marek,Mazur, Adam,Jankowski, Stefan,Kamiński, Zbigniew J.
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supporting information; experimental part
p. 20 - 22
(2010/03/03)
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- An improved process for the synthesis of DMTMM-based coupling reagents
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A simple, robust and high-yielding process for the preparation of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium tetrafluoroborate (DMTMM BF4) and hexafluorophosphate (DMTMM PF6) has been developed, which avoids the use of expensive or unusual reagents.
- Raw, Steven A.
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scheme or table
p. 946 - 948
(2009/05/27)
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- Synthesis of water-soluble large naturalised dyes through double glycoconjugation
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Recently we started to develop a new class of dyes based upon the glycoconjugation of disperse dyes with mono- or disaccharides. We used the term "naturalised" to describe these dyes because we used natural lactose in the glycoconjugation process, and also because they are similar to real natural dyes, the hydrosolubility of which is based upon the saccharidic moiety attached to the chromophore, as in carminic acid or carthamin. Synthetic dyes submitted to the process of naturalisation consist of small chromophoric molecules, prevalently azoic, whereas larger dye molecules with a higher mass did not show appreciable solubility in water when a single molecule of lactose was added through a bivalent spacer, which is in contrast to the smaller dyes. To overcome this difficulty, herein we present the first approach to the insertion of two lactose units by a double glycoconjugation process. The procedure here presented allows the successful insertion of a spacer, the malonic acid, which can be linked with two lactose units so that even large dyes become soluble. Wiley-VCH Verlag GmbH & Co. KGaA.
- Isaad, Jalal,Rolla, Massimo,Bianchini, Roberto
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body text
p. 2748 - 2764
(2009/08/16)
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- A PROCESS OF MAKING IMATINIB
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The invention relates to a process which comprises reacting, in a solvent, the compound of formula (2) with a compound of formula (3) or a salt thereof in the presence of a 1,3,5-triazine coupling agent, to form imatinib of formula (1) or a salt thereof, and to the use of 1, 3, 5-triazine compounds in making imatinib.
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Page/Page column 8-9
(2009/07/25)
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- Thixotropic twin-dendritic organogelators
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Twin-dendritic organogelators have been prepared through selective functionalization of N-(3-aminopropyl)-1,3-propanediamine (APPDA) with self-assembling dendrons by using 1,1′-carbonyldiimidazole (CDI). Subsequent modification of the APPDA linker provided an additional degree of structural diversity by which to tailor the gelator self-assembly in bulk or in the gel state. These compounds are able to gel cyclohexane, toluene, n-butyl acetate, ethyl acetate, dichloromethane, and tetrahydrofuran. 3,4-Disubstituted apical branching units provided the most efficient organogelators and show a propensity to form thixotropic gels, wherein the gel recovers its elasticity after being subjected to shear. Structural and retrostructural analysis of the twin-dendritic organogelators reveals the bulk structural characteristics to be indicative of the subsequent gel properties. Diverse self-organized arrays were identified in bulk and all are able to form gels, thus indicating the role of quasiequivalence in mediating self-assembly in the gel state. Furthermore, we have found that porous columnar mesophases provide a strategy by which to prepare thixotropic gels. We demonstrate the importance of weak lateral hydrogen bonding within a column stratum versus hydrogen bonding along the length of the column for forming porous columnar mesophases and, by extension, thixotropic gels.
- Percec, Virgil,Peterca, Mihai,Yurchenko, Michael E.,Rudick, Jonathan G.,Heiney, Paul A.
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p. 909 - 918
(2008/12/20)
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- Structural basis for superiority of N-methyl-N-(4,6-dimethoxy-1,3,5- triazin-2-yl)morpholinium tetrafluoroborate as modular coupling reagent crystal structures of N-methyl-N-(4,6-dimethoxy-1,3,5-triazin-2-yl)morpholinium and -piperidinium tetrafluoroborates and their demethylation products
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Structural characteristics of tetrafluoroborates of N-methylated N-(4,6-dialkoxy-1,3,5-triazin-2-yl)-morpholine and -piperidine, as determined by X-ray diffraction study, not only explain their good performance as modular coupling reagents in the peptide synthesis but also their higher stability than appropriate chlorides, which degrade easily through demethylation. Not expected axial orientation of 4,6-dialkoxy-1,3,5-triazinyl substituent at the quaternary N atom of the aliphatic ring observed in the crystal state has been confirmed in a solution by NMR technique. Quarternary triazinyl ammonium salts have been found as excellent modular coupling reagents, particularly in peptide syntheses. Crystal structure determination of N-methyltriazinylmorpholinium and -piperidinium tetrafluoroborates as well as their demethylated products provides a structural reason for the observed reaction. Namely, formation of very stable guanidine system around C(2) atom in 2-morpholine- and 2-piperidine-s-triazines is controlled thermodynamically, while the difference in stability of chlorides and tetrafluoroborates (being superior) of quarternary N-methyl-N- triazinylmorpholinium (or piperidinium) results from conservative conformation of their cations, which hinders an access of large and less nucleophilic tetrafluoroborate anion than Cl- to the methyl carbon atom.
- Olczak,Blaszczyk M,Glowka,Kolesinska,Kaminski
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p. 1413 - 1423
(2008/12/20)
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- Chemoselective activation of nucleoside 3′-O-methylphosphonothioates with 1,3,5-triazinyl morpholinium salts
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(Chemical Equation Presented) Chemoselective and stereospecific O-activation of 2′-deoxy-nucleoside 3′-O-methylphosphonothioates 5 with N-methyl-N-4,6-dimethoxy-1,3,5-triazin-2-yl morpholinium salts results in formation with retention of configuration of 5′-O-DMT-2′- deoxynucleoside 3′-O-(4,6 dimethoxy-1,3,5-triazin-2-yl methylphosphonothioates (7). Active esters 7 are convenient intermediates for hydrolytic interconversion of Rp-5 into Sp-5 and can be used as monomers for stereoselective synthesis of dinucleoside (3′,5′)-methyl phosphonothioates.
- Wozniak, Lucyna A.,Gora, Marcin,Stec, Wojciech J.
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p. 8584 - 8587
(2008/03/12)
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- N-triazinylammonium tetrafluoroborates. A new generation of efficient coupling reagents useful for peptide synthesis
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A new generation of triazine-based coupling reagents (TBCRs), designed according to the concept of "superactive esters", was obtained by treatment of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium (DMTMM) chloride with lithium or silver tetrafluoroborate. The structure of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium tetrafluoroborate was confirmed by X-ray diffraction. Activation of carboxylic acids by using this reagent proceeds via triazine "superactive ester". The coupling reagent was successfully used for the synthesis of Z-, Boc-, and Fmoc-protected dipeptides derived from natural and unnatural sterically hindered amino acids and for fragment condensation, in 80-100% yield and with high enantiomeric purity. The manual SPPS of the ACP(65-74) peptide fragment (H-Val-Gln-Ala-Ala- lle-Asp-Tyr-Ile-Asn-Gly-OH) proceeded significantly faster than with TBTU or HATU, as well as the automated SPPS of the same fragment gave a purer product than by using TBTU or PyBOP. The reagent was also demonstrated to be efficient in on-resin head-to-tail cyclization of constrained cyclopeptides, in SPPS synthesis of Aib peptides, and in the synthesis of esters from appropriate acids, alcohols, and phenols. The high efficiency and versatility of this new generation of TBCRs confirm, for the first time, the usefulness of the concept of "superactive esters" in rational design of the structure of coupling reagents.
- Kaminski, Zbigniew J.,Kolesinska, Beata,Kolesinska, Justyna,Sabatino, Giuseppina,Chelli, Mario,Rovero, Paolo,Blaszczyk, Michal,Glowka, Marek L.,Papini, Anna Maria
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p. 16912 - 16920
(2007/10/03)
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- METHODS AND COMPOUNDS PRODUCING DIPEPTIDYL PEPTIDASE IV INHIBITORS AND INTERMEDIATES THEREOF
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Methods and compounds for production of cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV are provided
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- Method for preserving quaternary ammonium salt
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A method of improving the stability of a quaternary ammonium salt and a method of efficiently preparing the quaternary ammonium salt having improved stability.
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- Processes for preparing triazine compounds and quaternary ammonium salts
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In the process of the invention to prepare 4,6-dialkoxy-1,3,5-triazine-2-halide by reacting a cyanuric halide with an alcohol compound such as methanol in the presence of an alkali such as sodium hydrogencarbonate, the water content present in the reaction system at the beginning of the reaction is controlled to not more than 0.5 mol based on 1 mol of the cyanuric halide or the water content present in the reaction system during the period of the reaction is controlled to not more than 2.5 mol based on 1 mol of the cyanuric halide. According to the invention, 4,6-dialkoxy-1,3,5-triazine-2-halide can be prepared in a high yield.
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- Approach to green chemistry of DMT-MM: Recovery and recycle of coproduct to chloromethane-free DMT-MM
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A simple procedure for the isolation of 2-hydroxy-4,6-dimethoxy-1,3,5-triazine (HO-DMT), a coproduct arising from dehydrating condensation using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) has been established. HO-DMT can be recycled by treatment with POCl3 to give 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT), which is further converted to DMT-MM. Alternatively, reaction with triflic anhydride followed by addition of N-methylmorpholine gives DMT-MM triflate.
- Kunishima, Munetaka,Hioki, Kazuhito,Wada, Ayako,Kobayashi, Hiroko,Tani, Shohei
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p. 3323 - 3326
(2007/10/03)
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- METHOD FOR STORING QUATERNARY AMMONIUM SALT
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A method of improving the stability of a quaternary ammonium salt and a method of efficiently preparing the quaternary ammonium salt having improved stability.
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- 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride: An efficient condensing agent leading to the formation of amides and esters
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4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) was quantitatively synthesized by the coupling of 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) and N- methylmorpholine (NMM) in THF, and characterized. Condensation of carboxylic acids and amines by DMTMM proceeded effectively in THF to give the corresponding amides in good yields. The corresponding esters can be obtained by esterification of carboxylic acids with DMTMM in methanol, ethanol, isopropyl alcohol, or t-butyl alcohol in the presence of NMM. The amount of alcohols can be reduced to a stoichiometric amount by conducting the reaction in THF. Since the reactions proceed under atmospheric conditions without drying of the solvent, and the co- product (4,6-dimethoxy-1,3,5-triazin-2(1H)-one) arising from DMTMM after condensation can be readily removed by extraction, this method is a very practical one.
- Kunishima, Munetaka,Kawachi, Chiho,Morita, Jun,Terao, Keiji,Iwasaki, Fumiaki,Tani, Shohei
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p. 13159 - 13170
(2007/10/03)
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- Synthesis and characterization of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)- 4-methylmorpholinium chloride
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4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) was quantitatively synthesized by the coupling of 2-chloro-4,6- dimethoxy-1,3,5-triazine and N-methylmorpholine in THF, and fully characterized. Condensation of carboxylic acids and amines by DMTMM proceeded effectively in THF to give the corresponding amides in good yield.
- Kunishima, Munetaka,Kawachi, Chiho,Iwasaki, Fumiaki,Terao, Keiji,Tani, Shohei
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p. 5327 - 5330
(2007/10/03)
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- A Study on the Activation of Carboxylic Acids by Means of 2-Chloro-4,6-dimethoxy-1,3,5-triazine and 2-Chloro-4,6-diphenoxy-1,3,5-triazine
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Activation of carboxylic function by means of 2-chloro-4,6-disubstituted-1,3,5-triazines 1 and 2 leading to triazine esters was found to be a multistep process with participation of quarternary triazinylammonium salts 3-6 as the intermediates, with the rate of reaction strongly dependent on the structure of the tertiary amine. The studies on alkylation of tertiary amines with CDMT revealed the two-step process AN + DN, and zwitterionic addition product 9 was identified by 1H NMR spectroscopy. Semiempirical modeling of the reaction as well as measured nitrogen and chlorine isotope effects also support this mechanism.
- Kaminski,Paneth,Rudzinski
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p. 4248 - 4255
(2007/10/03)
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