Synthesis and pyrolysis of ABC type miktoarm star copolymers with polystyrene,poly(lactic acid) and poly(ethylene glycol) arms

An ABC type miktoarm star copolymer possessing polystyrene (PS), poly(lactic acid) (PLA) and poly(ethylene glycol) (PEG) arms was synthesized by combining Atom Transfer Radical Polymerization (ATRP) and Ring Opening Polymerization (ROP) with two click chemistries, namely thiol–ene and copper catalyzed azide–alkyne cycloaddition (CuAAC). For this purpose, a core 1-(allyloxy)-3-azidopropan-2-ol with allyl and azide functionalities was synthesized in two steps. Then, clickable polymers, polystyrene with thiol functionality (PS–SH) and poly(ethylene glycol) with alkyne functionality (PEG–acetylene) were independently prepared. As the first step of the grafting onto process, PS–SH was thiol–ene clicked onto the core to yield PS–N₃–OH. The second arm was then incorporated onto the core by the Ring Opening Polymerization (ROP) of l-(?)-Lactide (LA) using as PS–N₃–OH initiator and tin(II) 2-ethylhexanoate as catalyst. Finally, alkyne–PEG–acetylene was bonded to the resulting PLA–PS–N₃ using CuAAC click reaction. All intermediates, related polymers at different stages and final PS–PLA–PEG miktoarm star copolymer were characterized by ¹H NMR, FT-IR, SEC and DP-MS analyses. Direct pyrolysis mass spectrometry, (DP-MS) analyses of PS–PLA–PEG and all intermediate polymers indicated that the decomposition of PS and PEG chains occurred almost independently, following the degradation mechanisms of the corresponding homopolymers. On the other hand, during the pyrolysis of PS–PLA–PEG, elimination of H₂O during the decomposition of PEG chains at the early stages of pyrolysis caused hydrolysis of PLA chains and increased the yields of CO₂, CO and units involving unsaturation and/or crosslinked structure.     

Ene-yne-ene and ene-yne-yne metathesis of norbornene derivatives

Norbornene derivatives 4 and 5 containing sidechains bearing an internal alkyne and either a terminal alkene or a terminal alkyne were found to undergo a cascade of metathesis reactions when treated with ruthenium based metathesis catalysts to form highly functionalised pentacyclic products. The reactions illustrate an interesting difference in reactivity between Grubbs’ catalyst and the second generation catalyst, with the former being more reactive for the early steps of the cascade.     

Click reactions in chitosan chemistry

The review provides the first generalized and systematized information on the use of click reactions in chitosan chemistry for the preparation of novel polymers with attractive physicochemical and biological properties. The reactions of copper-catalyzed azide—alkyne cycloaddition and the click reactions of chitosan derivatives occurring in the absence of salts or metal complexes are discussed in detail. The data on the pre-click modification of chito-san (i.e., the introduction of azide function, alkyne fragment, highly dipolarophilic moieties, and thiol group into the polymer) are reviewed. Special attention is given to the application of new chitosan derivatives obtained by click modification.     

Synthesis and functionalization of dendron‐polymer conjugate based hydrogels via sequential thiol‐ene “click” reactions

Fabrication and functionalization of hydrogels from well‐defined dendron‐polymer‐dendron conjugates is accomplished using sequential radical thiol‐ene “click” reactions. The dendron‐polymer conjugates were synthesized using an azide‐alkyne “click” reaction of alkene‐containing polyester dendrons bearing an alkyne group at their focal point with linear poly(ethylene glycol)‐bisazides. Thiol‐ene “click” reaction was used for crosslinking these alkene functionalized dendron‐polymer conjugates using a tetrathiol‐based crosslinker to provide clear and transparent hydrogels. Hydrogels with residual alkene groups at crosslinking sites were obtained by tuning the alkene‐thiol stoichiometry. The residual alkene groups allow efficient postfunctionalization of these hydrogel matrices with thiol‐containing molecules via a subsequent radical thiol‐ene reaction. The photochemical nature of radical thiol‐ene reaction was exploited to fabricate micropatterned hydrogels. Tunability of functionalization of these hydrogels, by varying dendron generation and polymer chain length was demonstrated by conjugation of a thiol‐containing fluorescent dye. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 926–934     

A photolabile protection strategy for terminal alkynes

We present a strategy for photolabile protection of terminal alkynes. Several photo-caged alcohols were synthesized via mild copper(II)-catalyzed substitution between tertiary propargylic alcohols and 2-nitrobenzyl alcohol to build up robust, base stable o-nitrobenzyl (NB) photo-cleavable compounds. We compare the new photolabile protecting group with the commonly used alkyne protecting group, 2-methyl-3-butyn-2-ol and the results show that NB ethers are stable under the cleaving conditions for the cleavage of methylbutynol protected alkynes. Additionally, we present the synthesis of photo-cleavable NB derivatives containing thiol groups that can serve as agents for photoinduced surface functionalization reactions.     

New insights into the water-solubilisation of fluorophores by post-synthetic "click" and Sonogashira reactions

New synthetic methodologies for the efficient chemical conversion of hydrophobic fluorescent dyes into bioconjugable and water-soluble derivatives are described. The combined use of an original sulfonated terminal alkyne and a metal-mediated reaction, namely the copper-catalysed Huisgen 1,3-dipolar cycloaddition ("click" reaction) or the Sonogashira cross-coupling, is the cornerstone of these novel post-synthetic sulfonation approaches.     

Straightforward synthesis of bioconjugatable azo dyes. Part 2: Black Hole Quencher-2 (BHQ-2) and BlackBerry Quencher 650 (BBQ-650) scaffolds

A further extension of the efficient synthetic methodology described in Part 1, to the aromatic bis-diazo scaffold of Black Hole Quencher-2 dye is presented. Bioconjugatable derivatives bearing either azido, terminal alkyne, or maleimide reactive group were easily obtained as well as the free-phenol form of BlackBerry® Quencher 650 (BBQ-650®) initially developed by Berry & Associates, Inc. Company. The efficient conjugation ability of azido- and maleimide-quenchers was demonstrated through the facile preparation of the first water-soluble and formylated BHQ-2 dyes and a FRET-based probe suitable for the in vitro/in cellulo detection of a cancer-associated protease namely urokinase-type plasminogen activator.     

Novel oxidizing properties of p-methoxybenzenetellurinic acid anhydride

The title compound has proved to be a mild oxidizing agent like the corresponding telluroxide or tellurone towards thiol, phosphine, thioamide, thiourea, thionoester, and benzylic alcohol. In addition, it serves as a selective catalyst for the hydration of terminal alkyne.     

Enhancing the Activity of Surface Immobilized Antimicrobial Peptides Using Thiol-Mediated Tethering to Poly(ethylene glycol)

Considering the need for versatile surface coatings that can display multiple bioactive signals and chemistries, the use of more novel surface modification methods is starting to emerge. Thiol-mediated conjugation of biomolecules is shown to be quite advantageous for such purposes due to the reactivity and chemoselectivity of thiol functional groups. Herein, the immobilization of poly(ethylene glycol) (PEG) and antimicrobial peptides (AMPs) to silica colloidal particles based on thiol-mediated conjugation techniques, along with an assessment of the antimicrobial potential of the functionalized particles against Pseudomonas aeruginosa and Staphylococcus aureus is investigated. Immobilization of PEG to thiolated Si particles is performed by either a two-step thiol–ene “photo-click” reaction or a “one-pot” thiol–maleimide type conjugation using terminal acrylate or maleimide functional groups, respectively. It is demonstrated that both immobilization methods result in a significant reduction in the number of viable bacterial cells compared to unmodified samples after the designated incubation periods with the PEG-AMP-modified colloidal suspensions. These findings provide a promising outlook for the fabrication of multifunctional surfaces based upon the tethering of PEG and AMPs to colloidal particles through thiol-mediated biocompatible chemistry, which has potential for use as implant coatings or as antibacterial formulations that can be incorporated into wound dressings to prevent or control bacterial infections.     

Cobalt-catalyzed intermolecular [2 + 2 + 2] cycloaddition for the synthesis of 1,3-cyclohexadienes

A cobalt(I)-catalyzed [2 + 2 + 2] cycloaddition reaction between an internal acceptor-substituted alkyne and a terminal alkene leads to the formation of regiochemically enriched polysubstituted 1,3-cyclohexadiene derivatives in acceptable yields when methyl butynoate is used, whereas regiochemically pure products are formed in good yields form phenyl propyonate. The concurrent cyclotrimerization reaction of the alkyne to the corresponding benzene derivative is dependent on the sterical bulk of the alkyne and is considerably reduced with the sterically more hindered alkyne.     

Cp*RuCl(COD) in catalysis: A unique role in the addition of diazoalkane carbene to alkynes

The catalytic transformations of functional alkynes with diazoalkanes in the presence of the catalyst precursor RuCl(COD)Cp* are presented. They show the unique role played by the Ru(X)Cp* moiety in catalysis and that the nature of the formed products strongly depends on the alkyne functionality. Simple alkynes generate dienes via double diazoalkane carbene addition to the triple bond. Enynes with terminal triple bond lead to alkenyl bicyclo[x.1.0]alkanes, including bicyclic aminoacid derivatives. 1,6-enynes with disubstituted propargylic carbon produce in priority alkenyl alkylidene cyclopentanes. 1,6-Allenynes offer the direct access to alkenyl alkylidene bicyclo[3.1.0]hexanes. Propargylic carboxylates lead to conjugated dienes by coupling of the diazoalkane carbene with the alkyne terminal carbon and 1,2-shift of the carboxylate. All catalytic reactions can be explained by the initial formation of the 16 electron RuCl(CHR)Cp* moiety giving first a 2+2 cycloaddition with the alkyne triple bond.     

Synthesis of tadpole polymers via triple click reactions: Copper‐catalyzed azide–alkyne cycloaddition,diels–alder,and nitroxide radical coupling reactions

We designed a trifunctional initiator ( 3 ) containing anthracene, bromide, and OH functionalities and subsequently used as an initiator in atom transfer radical Polymerization (ATRP) of styrene to yield linear polystyrene (PS) with α‐anthracene, OH, and ω‐bromide terminal groups, of which bromide is later transformed into azide to result in the linear anthracene‐, OH‐, and azide‐terminated PS (l‐α‐anthracene‐OH‐ω‐azide‐PS). The copper‐catalyzed azide–alkyne cycloaddition reaction between l‐α‐anthracene‐OH‐ω‐azide‐PS and α‐furan‐protected‐maleimide‐ω‐alkyne linkage, 4 afforded the linear anthracene‐, OH‐, and maleimide‐terminated PS. The cyclization via intramolecular Diels–Alder click reaction of this linear PS and the subsequent conversion of the hydroxyl into bromide resulted in the cyclic PS with one bromide located on the ring, (c‐PS)‐Br. Finally, the c‐PS‐Br was clicked with either well‐defined tetramethylpiperidine‐1‐oxyl‐terminated poly(ethylene glycol) (PEG) or poly(ε‐caprolactone) (PCL) yielding the tadpole polymer, (c‐PS)‐b‐PEG or (c‐PS)‐b‐PCL. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Facile synthesis of beta-organotellurobutenolides via electrophilic tellurolactonization of alpha-allenoic acids

We report a convenient and highly efficient method for the synthesis of beta-organotellurobutenolides by the aryltellurenyl halides-induced electrophilic tellurolactonization of alpha-allenoic acids under mild conditions. The resulting beta-organotellurobutenolides can be utilized as precursors for versatile butenolide derivatives through a substitution reaction with organocuprate reagent or Pd/Cu(I)-catalyzed cross-coupling with terminal alkyne.     

Synthesis of novel 1-benzyl/aryl-4-{[(1-aryl-1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazol-4-yl)methoxy]methyl}-1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazole derivatives and evaluation of their antimicrobial activity

A series of 1-benzyl/aryl-4-{[(1-aryl-1H-1,2,3-triazol-4-yl)methoxy]methyl}-1H-1,2,3-triazole derivatives were synthesized via Cu(I) catalyzed reaction between terminal alkyne and substituted aryl or benzyl azides. The synthesized triazoles were characterized by 1H NMR, 13C NMR, IR, and mass spectral techniques. All the synthesized compounds were screened for their antimicrobial activity.     

Formation of C-Glycosides by Ferrier Reaction

Peracetylated glycals were treated with terminal alkyne derivatives under Lewis acid catalysis to result in the formation of the pure α- or β- anomerically substituted hex-2-enopyranosides carrying 2(E)-halogenated olefins.     

Modular synthesis of a block copolymer with a cleavable linkage via “click” chemistry

A diblock copolymer poly(ethylene glycol)-block-polystyrene or PEG-b-PS with an olefinic double bond at the PEG and PS junction has been prepared by modular synthesis via “click” chemistry. This involved the synthesis of PS by atom transfer radical polymerization and the nucleophilic substitution of the terminal bromide group with azide to yield azide-terminated PS. PEG with an alkynyl terminal group was prepared from reacting carboxyl-end-functionalized PEG with 4-hydroxybut-2-enyl prop-2′-ynyl succinate, which contained an alkynyl group as well as an olefin group. The PS and PEG polymers were linked via the 1,3-dipolar cycloaddition of the end azide and alkyne groups. The obtained copolymer was characterized by ¹H NMR spectroscopy and size exclusion chromatography (SEC). SEC analysis indicated that the diblock copolymer produced could be readily cleaved by ozonolysis to regenerate the constituent homopolymers.     

An efficient reagent for 5′-azido oligonucleotide synthesis

A new bromohexyl phosphoramidite was synthesized and used for the introduction of an azide function at the 5′-end of oligonucleotides after a treatment on solid support with sodium azide and sodium iodide. The corresponding 5′-azido oligonucleotide could be further used for ‘Click’ conjugation with alkyne derivatives or by Staudinger ligation.     

Alkynylation of ferrocene by terminal alkynes. Part I. A simple one-step synthesis of ferrocenylacetylenes

Ferrocene reacts with terminal alkynes in the presence of copper and iron salts to give 1-ferrocenyl-2-R-alkynes (R - substituent). This direct cross-coupling of ferrocenyl and alkynyl moieties allows for the preparation of ferrocenyl substituted alkynes in one step directly from ferrocene and a terminal alkyne avoiding prior preparation of other derivatives of ferrocene. This new synthetic reaction does not require special conditions, is promoted by the action of common iron and copper salts, and tolerates the presence of functional groups in the alkyne.     

Ene-yne metathesis of polyunsaturated norbornene derivatives

Norbornene derivatives bearing endo-substituents in the 5- and 6-positions were studied as substrates for ene-yne metathesis cascades. Substrates which contained an internal alkyne and a terminal alkene or alkyne in each sidechain were found to undergo a metathesis cascade leading to pentacyclic bis-dienes and bis-trienes. Attempts to extend the chemistry further to sidechains containing two internal alkynes or two internal alkynes and a terminal alkene were not successful with the first generation Grubbs' catalyst. However, the substrate containing two internal alkynes did react with the second generation Grubbs' catalyst to give a tetra-diene containing product.