Efficient DMTMM Promoted Nucleoside Loading of CPG Solid Support for Oligonucleotide Synthesis

Abstract

A simple and efficient process for the attachment of protected 2′‐deoxynucleosides to the solid support controlled pore glass (CPG) via succinyl linkage using the mild, non‐carbodiimide dehydrating agent 4‐(4,6‐dimethoxy‐1,3,5‐triazin‐2‐yl)‐4‐methylmorpholinium chloride (DMTMM) has been developed. The protocol is cost effective, does not require anhydrous conditions and is easy to implement.     

Derivatization of sialic acids for stabilization in matrix‐assisted laser desorption/ionization mass spectrometry and concomitant differentiation of α(2 → 3)‐ and α(2 → 6)‐isomers

Sialylated carbohydrates usually decompose by loss of sialic acid when ionized by matrix‐assisted laser desorption/ionization (MALDI) as the result of the labile carboxylic proton. Stabilization has previously been achieved by forming methyl esters with methyl iodide, a procedure that eliminates the labile proton. In this paper, we describe an alternative procedure for methyl ester formation that provides information on the sialic acid linkage directly from the MALDI spectrum. The sugars were desalted, dissolved in methanol, and treated with 4‐(4,6‐dimethoxy‐1,3,5‐triazin‐2‐yl)‐4‐methylmorpholinium chloride (DMT‐MM). After removal of the solvent, the products were transferred directly to the MALDI target and examined from 2,5‐dihydroxybenzoic acid. Small amounts of N‐glycans derived from biological sources benefited from an additional clean‐up stage involving Nafion 117. α(2 → 6)‐Linked sialic acid produced only methyl esters whereas α(2 → 3)‐linked sialic acids were converted into their lactones providing a 32 Da difference in mass. Negative ion collision‐induced decomposition (CID) mass spectra of these neutralized glycans provided information, in many cases, on the antenna of N‐linked glycans to which the variously linked sialic acids were attached. The method was applied to N‐linked glycans released from bovine fetuin and porcine thyroglobulin. Copyright © 2008 John Wiley & Sons, Ltd.     

Derivatization of chiral carboxylic acids with (S)‐anabasine for increasing detectability and enantiomeric separation in LC/ESI‐MS/MS

A simple and practical derivatization procedure for increasing the detectability and enantiomeric separation of chiral carboxylic acids in LC/ESI‐MS/MS has been developed. (S)‐Anabasine (ANA) was used as the derivatization reagent and rapidly reacted with carboxylic acids [3‐hydroxypalmitic acid (3‐OH‐PA), 2‐(β‐carboxyethyl)‐6‐hydroxy‐2,7,8‐trimethylchroman (γ‐CEHC), and etodolac] in the presence of 4‐(4,6‐dimethoxy‐1,3,5‐triazin‐2‐yl)‐4‐methylmorpholium chloride. The resulting ANA‐derivatives were highly responsive in ESI‐MS operating in the positive‐ion mode and gave characteristic product ions during MS/MS, which enabled sensitive detection using selected reaction monitoring; the detection responses of the ANA‐derivatives were increased by 20–160‐fold over those of the intact carboxylic acids and the limits of detection were in the low femtomole range (1.8–11 fmol on the column). The ANA‐derivatization was also effective for the enatiomeric separation of the chiral carboxylic acids; the resolution was 1.92, 1.75, and 2.03 for 3‐OH‐PA, γ‐CHEC, and etodolac, respectively. The derivatization procedure was successfully applied to a biological sample analysis; the derivatization followed by LC/ESI‐MS/MS enabled the separation and detection of trace amounts of 3‐OH‐PA in neonatal dried blood spot and γ‐CEHC in human saliva with a simple pretreatment and small sample volume.     

Novel synthesis of N‐substituted polyacrylamides: Derivatization of poly(acrylic acid) with amines using a triazine‐based condensing reagent

Poly(acrylic acid) (PAA) was derivatized through the reaction of its pendant carboxylic acid (CO₂H) groups with a wide range of amine‐terminated molecules. These molecules contained alkyl, hydroxyl, sulfonic acid, or perfluoroalkyl groups. N‐substitution of PAA was carried out by the simple addition of 4‐(4,6‐dimethoxy‐1,3,5‐triazin‐2‐yl)‐4‐methylmorpholinium chloride (DMTMM), a triazine‐based condensing reagent, to a mixture of PAA and amine‐terminated molecules. From proton nuclear magnetic resonance and infrared spectroscopy, it was confirmed that these functional molecules were introduced into the PAA side chain via amide bonds. By the alteration of the synthetic conditions, functional side‐chain contents of greater than 95% were achieved for aqueous reactions with taurine, ethanol amine, and butyl amine. Side‐chain conversion was limited to ≤80% for reactions with perfluoroalkyl amines in methanol. Thus, DMTMM is an attractive replacement for carbodiimide condensing reagents such as 1,3‐dicyclohexylcarbodiimide and 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 126–136, 2006     

Similar sulfonamides with different crystal structures: sulfasymazine and sulfatriazine

The crystal structures of 4‐amino‐N‐(4,6‐diethyl‐1,3,5‐triazin‐2‐yl)benzenesulfonamide, C₁₃H₁₇N₅O₂S, and 4‐amino‐N‐(4,6‐dimethoxy‐1,3,5‐triazin‐2‐yl)benzenesulfonamide, C₁₁H₁₃N₅O₄S, also known as sulfasymazine and sulfatriazine, respectively, are dominated by hydrogen‐bond interactions. All three potential hydrogen‐bond donors are employed in each case, resulting in a three‐dimensional network for sulfasymazine, while an entirely different hydrogen‐bonded layer structure is obtained for sulfatriazine. This study demonstrates the versatile nature of the hydrogen‐bonding capabilities in sulfonamides, even in structurally very similar molecules.     

Facile synthesis of pH‐responsive glycopolypeptides with adjustable sugar density

Well‐defined pH‐responsive glycopolypeptides were prepared by polymer‐analogous aqueous amide coupling of d ‐glucosamine to poly(α,l ‐glutamic acid) (PGA) using the coupling agent 4‐(4,6‐dimethoxy‐1,3,5‐triazin‐2‐yl)‐4‐methylmorpholinium chloride (DMT‐MM) without any organic solvents, additives, or buffers. Degrees of substitution (DS) up to 80% can be achieved, and the DS is adjustable by the molar ratio of DMT‐MM to PGA repeating units. Successful glycosylation of both low MW and high MW PGA was confirmed by ¹H NMR and FTIR spectroscopy as well as by an enhanced solubility at low pH. CD spectroscopy revealed that glycosylated PGAs with a DS up to 0.63 are able to undergo a pH‐responsive and reversible helix‐coil transition. However, for polymers with higher DS no transition occurs. A comparison with PGAs functionalized with monoethanolamine showed that the low helicity at high DS is not a steric effect due to the bulky sugar moieties, but a solvation effect. Preliminary turbidimetric tests with the lectin Concanavalin A indicate a biological activity of these glycosylated polypeptides. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 3925–3931     

Mild and Efficient Synthesis of Carboxylic Acid Anhydrides from Carboxylic Acids and Triazine Coupling Reagents

Abstract

Anhydrides of carboxylic acids were obtained in 53%–95% yield by treatment of appropriate carboxylic acids with 2‐chloro‐4,6‐dimethoxy‐1,3,5‐triazine (CDMT) or 2,4‐dichloro‐6‐methoxy‐1,3,5‐triazine (DCMT) in the presence of N‐methylmorpholine. It has been proved that synthesis proceeds via triazine active esters 3a,b, which are able to acylate carboxylate anion but not less nucleophilic carboxylic acid.     

Mild Amide‐Cleavage Reaction Mediated by Electrophilic Benzylation

An extremely mild method for amide‐cleavage by using the triazine‐based benzylating reagent 4‐(4,6‐diphenoxy‐1,3,5‐triazin‐2‐yl)‐4‐benzylmorpholinium trifluoromethanesulfonate (DPT‐BM), which spontaneously releases benzyl cation species when being dissolved at room temperature, has been developed. O‐Benzylation of the amide with DPT‐BM and the subsequent hydrolysis of the resulting intermediate benzyl imidate salt afford the corresponding amine and benzyl ester, which can be converted by hydrogenolysis into a carboxylic acid under neutral conditions. O‐Benzylation proceeds depending on both steric and electronic factors around the amide group. Thus, some amides have been selectively cleaved over other amides. Furthermore, intramolecular chemoselective cleavage of an amide group in the presence of an ester group was achieved. Such selective hydrolytic reactions cannot be performed with Meerwein reagents as well as under acidic or basic hydrolytic conditions.     

Development of a New Benzylating Reagent Spontaneously Releasing Benzyl Cation Equivalents at Room Temperature

A new O‐benzylating reagent, that is, 4‐(4,6‐diphenoxy‐1,3,5‐triazin‐2‐yl)‐4‐benzylmorpholinium trifluoromethanesulfonate (DPT‐BM), has been developed. Benzyl cation equivalents are generated from DPT‐BM by dissolving the compound in a solvent at room temperature under non‐acidic conditions. The benzylation of various alcohols by using a combination of DPT‐BM and magnesium oxide provided the benzyl ethers in good yields.     

4‐(4,6‐Dimethoxy‐1,3,5‐triazin‐2‐yl)‐4‐methylmorpholinium Toluene‐4‐sulfonate (DMT/NMM/TsO−) Universal Coupling Reagent for Synthesis in Solution

4‐(4,6‐Dimethoxy‐1,3,5‐triazin‐2‐yl)‐4‐methylmorpholinium toluene‐4‐sulfonate (DMT/NMM/TsO⁻), a representative member of the inexpensive and environmentally‐friendly N‐triazinylammonium family of sulfonates, has been found to be a very effective coupling reagent for the synthesis of amides, esters and peptides in solution. This study confirms the usefulness of DMT/NMM/TsO⁻ for peptide synthesis in solution, starting from Z‐, Fmoc‐, and Boc‐protected substrates as well as unnatural building blocks. Peptide synthesis with DMT/NMM/TsO⁻ produced high yields, with high crude product purity and low risk of racemization. In all cases, stoichiometric amounts of reagents were used and the standard synthetic procedure, without the need for time‐consuming optimization stages or expensive chromatographic purification. DMT/NMM/TsO⁻ was also found to be very useful for the synthesis of oligopeptides using a fragment coupling strategy.     

Synthesis of new 5‐acetyl(arylmethyliden)‐4‐thiazolidones

A new approach to the synthesis of new heterocyclic compounds with triazine and 4‐thiazolidone fragments in one molecule is developed. The synthesis methods comprise [2+3]‐cyclocondensation reactions essential in the preparative synthesis of 4‐thiazolidone derivatives. The reactions of S,N‐nucleophiles with C₂‐cyclization agents for the synthesis of a number of biologically active 2‐triazin‐4‐thiazolidones were investigated. The interaction of thiosemicarbazone of sym‐triazine with derivatives of α‐halogencarboxylic acids and maleic anhydride resulted in correspondent (2‐[2‐(4,6‐dichloro‐1,3,5‐triazin‐2‐yl)hydrazino]‐5‐(3,4,5‐ R‐p‐phenyl‐methyliden)‐1,3‐thiazol‐4‐ones obtained in the one‐step synthesis. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:392–396, 2010; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20631     

Synthesis of New Schiff Bases and Polycyclic Fused Thiopyranothiazoles Containing 4,6‐Dichloro‐1,3,5‐Triazine Moiety

New aromatic aldimines, isatine substituted ketimines based on (4,6‐dichloro‐1,3,5‐triazin‐2‐yl)‐hydrazine scaffold and polycyclic fused thiopyranothiazoles formed using hetero‐Diels‐Alder reactions starting from 4‐thioxo‐2‐thiazolidinones and 5‐norbornene‐2,3‐dicarboxylic acid triazino‐derivatives synthetic approach is described. The application of condensation and cyclocondensation reactions of N‐nucleophiles and carbonyl agents for synthesis a number of biologically active triazine derivatives is reported. Screening of anticancer activity in vitro yielded the most active compounds 3a , 8b , and 8f for different cell lines.     

Lignans from Phryma leptostachya L.

Three new lignans, haedoxan J ( 1 ), phrymarolin III ( 2 ), and phrymarolin IV ( 3 ), as well as eight known lignans, leptostachyol acetate, haedoxan A, 1‐(4,6‐dimethoxy‐1,3‐benzodioxol‐5‐yl)dihydro‐4‐(6‐methoxy‐1,3‐benzodioxol‐5‐yl)‐1H,3H‐furo[3,4‐c]furan‐3a(4H)‐yl acetate, 4‐(4,6‐dimethoxy‐1,3‐benzodioxol‐5‐yl)dihydro‐1‐(4‐methoxy‐1,3‐benzodioxol‐5‐yl)‐1H,3H‐furo[3,4‐c]furan‐3a(4H)‐yl acetate, 4‐[(4,6‐dimethoxy‐1,3‐benzodioxol‐5‐yl)oxy]dihydro‐1‐(6‐methoxy‐1,3‐benzodioxol‐5‐yl)‐1H,3H‐furo[3,4‐c]furan‐3a(4H)‐yl acetate, leptostachyol acetate C, 4‐(4,6‐dimethoxy‐1,3‐benzodioxol‐5‐yl)dihydro‐1‐(6‐methoxy‐1,3‐benzodioxol‐5‐yl)‐1H,3H‐furo[3,4‐c]furan‐3a(4H)‐yl acetate, and phrymarin II, were isolated from the plant Phryma leptostachya L. The structures of the new compounds were elucidated by analyzing their spectroscopic data and comparing with data reported in the literature.     

Study on side‐chain second‐order nonlinear optical polyimides based on novel chromophore‐containing diamines. II. Copolyimides possessing direct photolithographic features

Second‐order nonlinear optical copolyimides were prepared from a novel chromophore‐containing diamine, 4‐nitro‐4′‐[N‐(4,6‐di‐4‐aminophenylamino)‐1,3,5‐triazin‐2‐yl]aminoazobenzene, a codiamine, 4,4′‐diamino‐3,3′‐dimethyldiphenylmethane, and benzophenone‐3,3′,4,4′‐tetracarboxylic dianhydride by a traditional two‐step process, which includes a solution polycondensation followed by a chemical imidization. Some of the polyimides (PIs) obtained possessed direct photolithographic features, and good photolithographic patterns were easily obtained. All PIs exhibited high‐glass transition temperatures (235–246 °C) and high thermal‐decomposition temperatures. They were also soluble in strong polar aprotic solvents such as N‐methyl‐2‐pyrrolidone, dimethylacetamide, dimethylformamide, dimethyl sulfoxide, and γ‐butyrolactone. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 1419–1425, 2001     

C8N26H4: An Environmentally Friendly Primary Explosive with High Heat of Formation

The synthesis and characterization of the metal‐free polyazido compounds 3,6‐bis‐(2‐(4,6‐diazido‐1,3,5‐triazin‐2‐yl)‐hydrazinyl)‐1,2,4,5‐tetrazine ( 2 ) and 3,6‐bis‐(2‐(4,6‐diazido‐1,3,5‐triazin‐2‐yl)‐diazenyl)‐1,2,4,5‐tetrazine ( 4 ) are presented. Two compounds were characterized by NMR spectra, IR spectroscopy, mass spectrometry, and differential scanning calorimetry (DSC). Additionally, the structure of 2 was confirmed by single‐crystal X‐ray diffraction. Compounds 2 and 4 exhibit measured densities (1.755 g cm^?3 and 1.763 g cm^?3), good thermal stabilities (194 °C and 189 °C), high heat of formation (2114 kJ mol^?1 and 2820 kJ mol^?1), and excellent detonation performance (D, 8365 m s^?1 and 8602 m s^?1; P, 26.8 GPa and 29.4 GPa). Furthermore, compounds 2 and 4 have been tested for their priming ability to detonate RDX. The results indicate that the title compound 2 is a potential environmentally friendly alternative candidate to lead‐based primary explosives.     

Synthesis of [1,2‐a] benzimidazolo‐1,3,5‐triazin‐2‐thione, [1,2‐a] benzimidazolo‐1,3,5‐thiadiazin‐2‐thione, [1,2‐a] benzimidazolo‐1,3,5‐triazin‐2‐amine,and [1,2‐a] benzimidazol‐2‐yl amidrazone

N‐benzimidazol‐2‐yl imidate type 1 reacts with thiourea, carbon disulfide, cyanamide, and hydrazide to give, respectively, [1,2‐a] benzimidazolo‐1,3,5‐triazin‐2‐thione 2 , [1,2‐a] benzimidazolo‐1,3,5‐thiadiazin‐2‐thione 3 , [1,2‐a] benzimidazolo‐1,3,5‐triazin‐2‐amine 4 , and [1,2‐a] benzimidazol‐2‐yl amidrazone 5 with good yields. Structures elucidation of all newly synthesized heterocyclic compounds was based on the data of IR, ¹H NMR, ¹³C NMR, elemental analysis, and MS of some products. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:279–283, 2010; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20618     

Triggering Thermally Activated Delayed Fluorescence by Managing the Heteroatom in Donor Scaffolds: Intriguing Photophysical and Electroluminescence Properties

Establishment of the structure–property relationships of thermally activated delayed fluorescence (TADF) materials has become a significant quest for the scientific community. Herein, two new donors, 10H‐benzofuro[3,2‐b]indole (BFI) and 10H‐benzo[4,5]thieno[3,2‐b]indole (BTI), have been developed and integrated with a aryltriazine acceptor to design the green TADF emitters benzofuro[3,2‐b]indol‐10‐yl)‐5‐(4,6‐diphenyl‐1,3,5‐triazin‐2‐yl)benzonitrile ( BFICNTrz ) and 2‐(10H‐benzo[4,5]thieno[3,2‐b]indol‐10‐yl)‐5‐(4,6‐diphenyl‐1,3,5‐triazin‐2‐yl)benzonitrile ( BTICNTrz ), respectively. The physicochemical and electroluminescence properties of the compounds were tuned by exchanging the heteroatom in the donor scaffold. Intriguingly, the electronegativity of the heteroatom and the ionization potential of the donor unit played vital roles in control of the singlet–triplet energy splitting and TADF mechanism of the compounds. Both compounds showed similar singlet excited states that originated from the charge transfer (CT) states (¹CT), whereas the triplet excited states were tuned by the heteroatom in the donor unit. The origin of phosphorescence in the BTICNTrz emitter was CT emission from the triplet state (³CT), whereas that in the BFICNTrz emitter stemmed from the local triplet excited state (³LE). Consequently, BTICNTrz showed a small singlet–triplet energy splitting of 0.08 eV, compared with 0.26 eV for BFICNTrz . Thus, BTICNTrz showed efficient delayed fluorescence with a high quantum yield and a short delayed exciton lifetime, whereas BFICNTrz displayed weak delayed fluorescence with a relatively long lifetime. Furthermore, a BTICNTrz ‐based device exhibited a maximum external quantum efficiency (EQE) of 15.2 % and reduced efficiency roll‐off (12 %) compared with its BFICNTrz ‐based counterpart, which showed a maximum EQE of 6.4 % and severe efficiency roll‐off (55 %) at a practical brightness range of 1000 cd m^?2. These results demonstrate that the choice of subunit plays a vital role in the design of efficient TADF emitters.     

Intermolecular Charge‐Transfer Transition Emitter Showing Thermally Activated Delayed Fluorescence for Efficient Non‐Doped OLEDs

A novel molecular model of connecting electron‐donating (D) and electron‐withdrawing (A) moieties via a space‐enough and conjugation‐forbidden linkage (D‐Spacer‐A) is proposed to develop efficient non‐doped thermally activated delayed fluorescence (TADF) emitters. 10‐(4‐(4‐(4,6‐diphenyl‐1,3,5‐triazin‐2‐yl) phenoxy) phenyl)‐9,9‐dimethyl‐9,10‐dihydroacridine (DMAC‐o‐TRZ) was designed and synthesized accordingly. As expected, it exhibits local excited properties in single‐molecule state as D‐Spacer‐A molecular backbone strongly suppress the intramolecular charge‐transfer (CT) transition. And intermolecular CT transition acted as the vital radiation channel for neat DMAC‐o‐TRZ film. As in return, the non‐doped device exhibits a remarkable maximum external quantum efficiency (EQE) of 14.7 %. These results prove the feasibility of D‐Spacer‐A molecules to develop intermolecular CT transition TADF emitters for efficient non‐doped OLEDs.     

A novel (4,6)‐connected double‐layered BaII coordination polymer based on the flexible tricarboxylate ligand 2,2′,2′′‐[1,3,5‐triazine‐2,4,6‐triyltris(sulfanediyl)]triacetic acid

In the title compound, poly[[triaqua{μ₄‐2‐[4,6‐bis(carboxymethylsulfanyl)‐1,3,5‐triazin‐2‐ylsulfanyl]acetato}{μ₂‐2‐[4,6‐bis(carboxymethylsulfanyl)‐1,3,5‐triazin‐2‐ylsulfanyl]acetato}barium(II)] monohydrate], {[Ba(C₉H₈N₃O₆S₃)₂(H₂O)₃]·H₂O}_n, each Ba^II atom is nine‐coordinated by six O atoms from carboxylate groups of four different 2‐[4,6‐bis(carboxymethylsulfanyl)‐1,3,5‐triazin‐2‐ylsulfanyl]acetate ligands and three O atoms from water molecules. The triazine ligand is partially deprotonated, as verified by intermolecular hydrogen‐bonding parameters, and adopts μ₂‐η¹:η¹ and μ₄‐η¹:η¹:η² coordination modes to connect the Ba^II centres, forming a novel double‐layered structure. Topological analysis indicates that the whole structure is a novel (4,6)‐connected net, considering the ligands and Ba^II centres as four‐ and six‐connected nodes, respectively.     

Synthesis of acrimarins from 1,3,5‐trioxygenated‐9‐acridone derivatives

1,3,5‐Trihydroxy‐9(10H)‐acridinone (1) was prepared from 3‐hydroxyanthranillic acid with phloroglucinol. 1,3‐Dihydroxy‐5‐methoxy‐9(10H)‐acridinone (2) was prepared from 3‐methoxyanthranillic acid and phloroglucinol. Methylation of 1 under different conditions gave 1‐hydroxy‐3,5‐dimethoxy (3), 1‐hydroxy‐3,5‐dimethoxy‐10‐methyl (4), 1‐hydroxy‐3,5‐dimethoxy‐4‐methyl (5), 1,3,5‐trimethoxy‐10‐methyl (6) and 1,3,5‐trimethoxy‐4,10‐dimethyl (7) analogues. Demethylation of 4 afforded the 1,3,5‐trihydroxy‐10‐methyl analogue 8. Condensation of acridones 1, 2, 3 and 4 individually with E‐suberenol (9) gave four novel acrimarins (acridone‐coumarin dimers) 10, 11, 12 and 13 respectively, while the acridone 8 gave previously reported acrimarin‐G (14).