Difluoromethylation and Difluoroalkylation of (
            <scp>H</scp>
            etero)Arenes

Zhang, Xingang

doi:10.1002/9783527824342.ch1

Cited by 6 publications

(6 citation statements)

References 127 publications

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“…This allows site-specific quantification and dynamic studies of cell-surface glycoproteins. 38,43,44 Even though we globally analyzed surface glycoproteins in cultured cells, Spiciarich et al recently employed metabolic labeling with ManNAz for the identification of sialoglycoproteins from the proteomes of human prostate cancer and normal tissues. The authors identified 972 proteins from both samples with about 50% of the proteins localized on the plasma membrane.…”

Section: Resultsmentioning

confidence: 99%

Surface Glycoproteomic Analysis Reveals That Both Unique and Differential Expression of Surface Glycoproteins Determine the Cell Type

et al. 2019

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Proteins on the cell surface are frequently glycosylated, and they are essential for cells. Surface glycoproteins regulate nearly every extracellular event, but compared with global analysis of proteins, comprehensive and site-specific analysis of surface glycoproteins is much more challenging and dramatically understudied. Here, combining metabolic labeling, click-chemistry and enzymatic reactions, and mass spectrometry-based proteomics, we globally characterized surface glycoproteins from eight popular types of human cells. This integrative and effective method allowed for the identification of 2172 N-glycosylation sites and 1047 surface glycoproteins. The distribution and occurrence of N-glycosylation sites were systematically investigated, and protein secondary structures were found to have a dramatic influence on glycosylation sites. As expected, most sites are located on disordered regions. For the sites with the motif N-!P-C, about one-third of them are located on helix structures, while those with the motif N-!P-S/T prefer strand structures. There is almost no correlation between the number of glycosylation sites and protein length, but the number of sites corresponds well with the frequencies of the motif. Quantification results reveal that besides cell-specific glycoproteins, the uniqueness of each cell type further arises from differential expression of surface glycoproteins. The current research indicates that multiple surface glycoproteins including their abundances need to be considered for cell classification rather than a single cluster of differentiation (CD) protein normally used in conventional methods. These results provide valuable information to the *

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Section: Resultsmentioning

confidence: 99%

Surface Glycoproteomic Analysis Reveals That Both Unique and Differential Expression of Surface Glycoproteins Determine the Cell Type

et al. 2019

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“…For these alternative substrates, LiBr was found to benefit the reaction efficiency. Compared to aryl bromides, aryl triflates provided the difluoromethylated arenes in relatively lower yields (30)(31)(32)(33)(34). Although adapting phenol-based substrates exhibited relatively lower reaction efficiency, this strategy trades off the tedious synthetic steps of the previous procedure to prepare arylborons for difluoromethylation, [24] thus showing an overall advantage in terms of synthetic convenience.…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, the difluoromethyl (CF 2 H) group is a hydroxyl and thiol bioisostere, [29] and a lipophilic hydrogen bond donor. [30] As such, it is also of great interest to prepare bioactive relevant difluoromethylated arenes [31][32][33][34][35][36][37] through this palladium-catalyzed reductive difluorocarbene transfer process.…”

Section: Introductionmentioning

confidence: 99%

Reductive Catalytic Difluorocarbene Transfer via Palladium Catalysis

et al. 2023

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A palladium‐catalyzed reductive difluorocarbene transfer reaction that tames difluorocarbene to couple with two electrophiles has been developed, representing a new mode of difluorocarbene transfer reaction. The approach uses low‐cost and bulk industrial chemical chlorodifluoromethane (ClCF2H) as the difluorocarbene precursor. It produces a variety of difluoromethylated (hetero)arenes from widely available aryl halides/triflates and proton sources, featuring high functional group tolerance and synthetic convenience without preparing organometallic reagents. Experimental mechanistic studies reveal that an unexpected Pd0/II catalytic cycle is involved in this reductive reaction, wherein the oxidative addition of palladium(0) difluorocarbene ([Pd0(Ln)]=CF2) with aryl electrophile to generate the key intermediate aryldifluoromethylpalladium [ArCF2Pd(Ln)X], followed by reaction with hydroquinone, is responsible for the reductive difluorocarbene transfer.

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“…167 Xiao et al combined pulse-chase labeling and multiplexed proteomics using TMT with glycoprotein enrichment to simultaneously determine the synthesis and degradation rates of over 700 glycoproteins from MCF7 cells. 168 In the near future, with the development of higher-plexed reagents and approaches, simultaneous analysis of more samples will be achievable.…”

Section: Deciphering Glycoprotein Functions and Propertiesmentioning

confidence: 99%

Recent Advances in Glycoproteomic Analysis by Mass Spectrometry

2019

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Glycosylation is one of the most common protein modifications and is essential for cells. This modification is exceptionally complex because glycans are highly diverse and can be covalently bound to several amino acid residues in proteins through various configurations. There are two major types of protein glycosylation, i.e., N-linked glycosylation in which glycans are attached to the side chain of asparagine and O-linked glycosylation referring to glycans being bound to the side chains of serine and threonine. 1,2 Glycosylation plays vital roles in cells, including determination of protein folding, trafficking and stability, and regulation of nearly every extracellular activity such as cell-cell communication and cellmatrix interactions. 3,4 Aberrant protein glycosylation is directly related to multiple diseases, including cancer, neurodegenerative disorders, pulmonary diseases, blood disorders, and genetic diseases. 5,6 Due to the importance and complexity of protein glycosylation in biological systems, there is a longstanding interest to develop innovative methods to study glycoproteins and apply them for biomedical research. Investigation of protein glycosylation has become more popular with the development of modern instrumentation and computational methods. According to a PubMed search using the keyword "glycosylation", 16 publications were listed during 1960-1970 while over 20 000 studies were reported in the past 10 years. With the growing interests in protein glycosylation, this trend is expected to continue in the next decades.Mass spectrometry (MS)-based proteomics provides an excellent opportunity to globally analyze proteins and their modifications. [7][8][9][10][11][12][13][14][15][16][17][18][19] Nonetheless, it is still extremely challenging to comprehensively analyze protein glycosylation. 20 Unlike many other modifications with a fixed structure for the modified group, such as phosphorylation, the diversity of glycans makes it more challenging to employ the commonly used database searching methods such as SEQUEST and Mascot to identify glycopeptides in bottom-up proteomics. Lowabundance glycoproteins in complex biological samples are also hindered for detection by many high-abundance nonglycoproteins. Furthermore, glycans can interfere with the fragmentation of the peptide backbone. 20,21 Innovative and effective methods are critical to overcome these hurdles and to allow for comprehensive analysis of glycoproteins using MS.

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Difluoromethylation and Difluoroalkylation of ( H etero)Arenes

Cited by 6 publications

References 127 publications

Surface Glycoproteomic Analysis Reveals That Both Unique and Differential Expression of Surface Glycoproteins Determine the Cell Type

Surface Glycoproteomic Analysis Reveals That Both Unique and Differential Expression of Surface Glycoproteins Determine the Cell Type

Reductive Catalytic Difluorocarbene Transfer via Palladium Catalysis

Recent Advances in Glycoproteomic Analysis by Mass Spectrometry

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