Investigating Ugi/Passerini Multicomponent Reactions for the Site-Selective Conjugation of Native Trastuzumab**

Site-selective modification of proteins has been the object of intense studies over the past decades, especially in the therapeutic field. Prominent results have been obtained with recombinant proteins, for which site-specific conjugation is made possible by the incorporation of particular amino acid residues or peptide sequences. In parallel, methods for the site-selective and site-specific conjugation of native and natural proteins are starting to thrive, allowing the controlled functionalization of various types of amino acid residues. Pursuing the efforts in this field, we planned to develop a new type of site-selective method, aiming at the simultaneous conjugation of two amino acid residues. We reasoned that this should give higher chances of developing a site-selective strategy compared to the great majority of existing methods that solely target a single residue. We opted for the Ugi four-centre three-component reaction to implement this idea, with the aim of conjugating the side-chain amine and carboxylate groups of two neighbouring lysine and aspartate/glutamate. Herein, we show that this strategy can give access to valuable antibody conjugates bearing several different payloads; furthermore, the approach limits the potential conjugation sites to only six on the model antibody trastuzumab.     

Suzuki Cross-Coupling Reaction with Genetically Encoded Fluorosulfates for Fluorogenic Protein Labeling

A palladium-catalyzed cross-coupling reaction with aryl halide functionalities has recently emerged as a valuable tool for protein modification. Herein, a new fluorogenic modification methodology for proteins, with genetically encoded fluorosulfate-l -tyrosine, which exhibits high efficiency and biocompatibility in bacterial cells as well as in aqueous medium, is described. Furthermore, the cross-coupling of 4-cyanophenylboronic acid on green fluorescent protein was shown to possess a unique fluorogenic property, which could open up the possibility of a responsive “off/on” switch with great potential to enable spectroscopic imaging of proteins with minimal background noise. Taken together, a convenient and efficient catalytic system has been developed that may provide broad utilities in protein visualization and live-cell imaging.     

Streamlined access to 2,3-dihydropyrazino[1,2-a]indole-1,4-diones via Ugi reaction followed by microwave-assisted cyclization

An efficient method is developed to construct drug-like 2,3-dihydropyrazino[1,2-a]indole-1,4-diones from 1H-indole-2-carboxylic acids, ethyl pyruvate, isocyanides, and primary amines via a one-pot, two-step procedure involving Ugi reaction and microwave-assisted cyclization.     

An Azo Coupling Strategy for Protein 3-Nitrotyrosine Derivatization

Herein, a strategy for the selective derivatization of 3-nitrotyrosine-containing proteins using the classic azo coupling reaction as the key step is described. This novel approach featured multiple advantages and was successfully applied to detect picomole levels of protein tyrosine nitration in biological samples.     

An emerging post‐polymerization modification technique: The promise of thiol‐para‐fluoro click reaction

Post‐polymerization modification (PPM) of polymers is extremely beneficial in terms of designing brand new synthetic pathways toward functional complex polymers. Fortunately, the new developments in the field of organic chemistry along with controlled/living radical polymerization (CLRP) techniques have enabled scientists to readily design and synthesize the functionalized‐polymers for wide range of applications via the PPM. In this regard, the reactivity of para‐fluorine atom in the fluorinated aromatic structures toward the nucleophilic substitution reactions has made the polymers possessing this group to become a very strong candidate that can undergo efficient PPM. Besides, it has been proven that the thiol‐functionalized compounds react with the para‐fluorine atom of the pentafluorophenyl group more rapidly and efficiently than the amine‐ and the hydroxyl‐functionalized compounds. Furthermore, the milder experimental conditions to achieve quantitative conversions have led to the reaction between the thiol and the structures possessing pentafluorophenyl groups to be referred to as a click‐type reaction. Given this information, this review article aims to present the scientific developments regarding the thiol‐para‐fluoro “click” (TPF‐click) chemistry, and its impact on PPM to construct novel polymeric structures. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 1181–1198     

Affinity‐Labeling‐Based Introduction of a Reactive Handle for Natural Protein Modification

A new chemical method to site‐specifically modify natural proteins without the need for genetic manipulation is described. Our strategy involves the affinity‐labeling‐based attachment of a unique reactive handle at the surface of the target protein, and the subsequent selective transformation of the reactive handle by a bioorthogonal reaction to introduce a variety of functional probes into the protein. To demonstrate this approach, we synthesized labeling reagents that contain: 1) a benzenesulfonamide ligand that directs specifically to bovine carbonic anhydrase II (bCA), 2) an electrophilic epoxide group for protein labeling, 3) an exchangeable hydrazone bond linking the ligand and the epoxide group, and 4) an iodophenyl or acetylene handle. By incubating the labeling reagent with bCA, the reactive handle was covalently attached at the surface of bCA through epoxide ring opening. Either after or before removing the ligand by a hydrazone/oxime‐exhange reaction, which restores the enzymatic activity, the reactive handle incorporated could be derivatized by Suzuki coupling or Huisgen cycloaddition reactions. This method is also applicable to the target‐specific multiple modification in a protein mixture. The availability of various (photo)affinity‐labeling reagents and bioorthogonal reactions should extend the flexibility of this strategy for the site‐selective incorporation of many functional molecules into proteins.     

Diversity-oriented pyrazol-3-one synthesis based on hydrazinodipeptide-like units prepared via the Ugi reaction

N-Cyanoacetyl-N′-trifluoroacetyl-N′-alkylhydrazines, prepared via hydrazino-Ugi reaction, provided different pyrazol-3-ones when exposed to mildly acidic and mildly basic conditions at 60 °C. These approaches offer a facile access to two different pyrazol-3-one-containing chemotypes in a diversity-oriented fashion, in only two chemical operations from simple precursors.     

Collision-induced reporter fragmentations for identification of covalently modified peptides

Collision-induced reporter fragmentations of the currently most important covalent peptide modifications as detected by tandem mass spectrometry are summarized. These fragmentations comprise the formation of reporter ions, which are preferentially immonium ions, immonium ion-derived fragments or side chain fragments. In addition, the reporter neutral loss reactions for covalently modified amino acid residues are summarized. For each individual covalent modification which can be recognized by a reporter fragmentation, the accurate mass shift and the gross formula shift of the modified amino acid residue are given. The same set of data is provided for the reporter fragmentations. Finally, an extensive accurate mass and gross formula list is presented as supplementary material, describing mostly regular and modified y₁ and dipeptide a and b ions, which are helpful for identification of the peptide ends of covalently modified peptides. Figure When modified peptides are fragmented by collision-induced dissociation in a tandem mass spectrometer, the modification is either lost as part of a charged fragment, so that a reporter ion for the modification is generated or it is lost as part of a neutral fragment, so that a modification-specific reporter neutral loss is observed in the fragment ion spectrum. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. Chien-Wen Hung and Andreas Schlosser contributed equally to this work.     

Analyse de la pyrolyse menagee du bois par un couplage TG-DSC-IRTF

This paper deals whith thermal degradation of wood at low pyrolysis temperature. Chemical modifications are investigated in order to explain the new properties of treated wood.

     

Ring‐Opening of Benzocyclobutenol with Mild Bases and Trapping with Dieneophiles

The treatment of benzocyclobutenol with a mild base has been investigated. This reaction results in an electrocyclic opening of the cyclobutene to the corresponding o‐quinodimethane, which has been successfully treated with aldehydes and electron‐deficient alkenes to form benzolactols and benzocyclohexenes respectively.     

Carbyne — the third allotropic form of carbon

The history of the discovery of carbyne, the chemical and physical methods used to obtain it, the analysis of its structure, and some of its properties are briefly considered. The prospects for its practical applications are discussedThis publication is based on a number of works on carbyne submitted for the Russian State Prize in the field of science and technology in 1993; performed at the A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences and the M. V. Lomonosov Moscow State University.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 450–463, March, 1993.     

Convenient ‘one-pot’ synthesis of 3,4-substituted tetrahydrothiophenes through tandem Michael-Henry and Michael-Michael reactions

In situ generated nitro alkenes underwent tandem Michael-Henry and Michael-Michael sequences leading to the ‘one-pot’ formation of 3,4-substituted tetrahydrothiophenes using the commercially available 1,4-dithiane-2,5-diol (the dimer of mercaptoacetaldehyde) or its 4-mercapto-2-butenoates derivatives as suitable bifunctional partners, respectively.     

Catalytic Isofunctional Reactions—Expanding the Repertoire of Shuttle and Metathesis Reactions

Transfer hydrogenation, alkene metathesis, and alkyne metathesis possess great value to the synthetic chemistry community. One of the key features of these processes is their reversibility, which can be attributed to the presence of the same number and type of functional groups in both the reactants and products, making these reactions isofunctional. These classic reactions have recently inspired the development of novel shuttle and metathesis reactions that offer great promise for synthetic chemistry. This Review describes and systematically categorizes both recent and older examples of shuttle and metathesis reactions other than transfer hydrogenation and alkene/alkyne metathesis.