Intermolecular C-H silylations of arenes and heteroarenes with mono-, bis-, and tris(trimethylsiloxy)hydrosilanes: control of silane redistribution under operationally diverse approaches.

Efficient catalytic protocols for C-H silylations of arenes and heteroarenes with sterically and electronically different hydrosiloxysilanes are disclosed. The silylations are catalyzed by a well-defined Rh-complex (1 mol%), derived from [Rh(1,5-hexadiene)Cl]2 and a bulky BINAP type ligand. This catalyst not only promotes C-Si bond formation affording the desired products in up to 95% isolated yield, but also can suppress the silane redistribution side reactions of HSiMe2(OTMS). The protocol can also be applied for the C-H silylations of more reactive HSiMe(OTMS)2 with a much lower catalyst loading (0.25 mol%) and even with sterically demanding HSi(OTMS)3. The steric bulk of the arene substituent and hydrosiloxysilane is a major factor in determining the regioselectivity and electronic effect as secondary. The current method can be performed under operationally diverse conditions: with/without a hydrogen scavenger or solvent.

Detection of Aberrant Glycosylation of Serum Haptoglobin for Gastric Cancer Diagnosis Using a Middle-Up-Down Glycoproteome Platform.

Gastric cancer is a frequently occurring cancer and is the leading cause of cancer-related deaths. Recent studies have shown that aberrant glycosylation of serum haptoglobin is closely related to gastric cancer and has enormous potential for use in diagnosis. However, there is no platform with high reliability and high reproducibility to comprehensively analyze haptoglobin glycosylation covering microheterogeneity to macroheterogeneity for clinical applications. In this study, we developed a middle-up-down glycoproteome platform for fast and accurate monitoring of haptoglobin glycosylation. This platform utilizes an online purification of LC for sample desalting, and an in silico haptoglobin glycopeptide library constructed by combining peptides and N-glycans to readily identify glycopeptides. In addition, site-specific glycosylation with glycan heterogeneity can be obtained through only a single MS analysis. Haptoglobin glycosylation in clinical samples consisting of healthy controls (n = 47) and gastric cancer patients (n = 43) was extensively investigated using three groups of tryptic glycopeptides: GP1 (including Asn184), GP2 (including Asn207 and Asn211), and GP3 (including Asn241). A total of 23 individual glycopeptides were determined as potential biomarkers (p < 0.00001). In addition, to improve diagnostic efficacy, we derived representative group biomarkers with high AUC values (0.929 to 0.977) through logistic regression analysis for each GP group. It has been found that glycosylation of haptoglobin is highly associated with gastric cancer, especially the glycosite Asn241. Our assay not only allows to quickly and easily obtain information on glycosylation heterogeneity of a target glycoprotein but also makes it an efficient tool for biomarker discovery and clinical diagnosis.