Linchpin-directed precise labeling of lysine in native proteins, purification, and analysis.

The proteins are critical building blocks of living systems and serve as a tool for their investigation and intervention. Their precision engineering enables its tuning and expands the functional landscape. Among various proteinogenic amino acids, high-frequency lysine offers a promising bioconjugation target. However, it is also among the most challenging candidates for homogeneous single-site modification. The linchpin-directed modification (LDM) addresses this concern by offering chemoselective, site-selective, and modular protein bioconjugation. The protocol outlines a general method for single-site modification of a native protein. At first, the selected LDM reagent constructs a stable bioconjugate through acylation of the Lys side chain. Subsequently, its chemically orthogonal handle creates an opportunity to install desired probes directly. Alternatively, the same group enables bioconjugate enrichment through ordered immobilization. The subsequent release, coupled with probe installation, renders analytically pure single-site tagged protein bioconjugate. The analysis of these constructs involves intact MS of protein bioconjugate, peptide mapping, and MS-MS for the site of modification and homogeneity.

Reported Catalytic Hydrofunctionalizations that Proceed in the Absence of Catalysts: The Importance of Control Experiments.

The enlarged landscape of catalysis lies in the heart of chemistry. As the journey has set a milestone in organic synthesis, its darker side has not entered into the limelight. Studies disclose that the reported reactions by using catalysts were also attainable in the absence of catalysts in many cases. This article presents a literature collection that includes the significance of control experiments in hydrofunctionalization reactions. Systematic analysis reveals that the catalysts are ambiguous and might be unessential in chemical reactions enlisted here.

Strategies to Control Hypervalent Iodine - Primary Amine Reactions.

The field of hypervalent iodine chemistry has been prevalent since 1886. Its journey from obscurity to coming into the limelight has witnessed many effective transformations which have benefited the synthetic community at large. The reactivity of primary amines with hypervalent iodine reagents causes difficulty in synthetic outcome or not feasible due to high exothermicity of amine iodine which is an acid base reaction. This minireview highlights the worthwhile reactivity of hypervalent iodine reagents with aromatic and aliphatic primary amines. Some recent literature has been discussed to make a clear understanding on how such high reactivity of primary amine is controlled by introducing modulation in either substrate or reaction conditions, most of which are carried out under ambient reaction conditions.

Iodine(III)-Enabled Distal C-H Functionalization of Biarylsulfonanilides.

Here we report a metal-free C-N coupling reaction for carbazole synthesis by distal (- meta) C-H bond functionalization. Nitrenium ion, a potential synthetic intermediate, was generated in situ from reactions of iodine(III) reagents and biarylsulfonanilides. Following, nitrenium ions were used for intramolecular dehydrogenative C-N coupling reactions via 1,2-alkyl (methyl or ethyl) migration by the expense of C-H bond functionalization at the distal position toward synthesis of 1,2,4-trialkyl-substituted carbazoles. The iodine(III) condition was either maintained by using a stoichiometric amount of phenyliodine diacetate (PIDA) or in-situ generated from iodobenzene (PhI)- meta-chloroperbenzoic acid ( mCPBA) combination.