Showing papers by "Gong Chen published in 2022"

Extendable stapling of unprotected peptides by crosslinking two amines with o-phthalaldehyde

Abstract: Peptide modification methods that do not rely on the cysteine residue are underdeveloped, and their development could greatly expand the current toolbox for peptide chemistry. During the course of preliminary investigations into the classical ortho-phthalaldehyde (OPA)-amine-thiol condensation reaction, we found that in the absence of thiol, OPA readily condenses with two primary alkyl amines to form a class of underexplored isoindolin-1-imine compounds under mild aqueous conditions. From the intramolecular version of this OPA-2amines reaction, an efficient and selective methodology using mild reaction conditions has been developed for stapling unprotected peptides via crosslinking of two amino groups in both an end-to-side and side-to-side fashion. The stapling method is superfast and broadly applicable for various peptide substrates with the reacting amino groups separated by a wide range of different amino acid units. The macrocyclization reactions of selected substrates are completed within 10 seconds at 5 mM concentration and within 2 minutes at 50 μM concentration. Importantly, the resulting cyclized peptides with an isoindolinimine linkage can be extended in a one-pot sequential addition manner with several different electron-deficient π electrophiles, thereby generating more complex structures.

Synthesis of N-acyl sulfenamides via copper catalysis and their use as S-sulfenylating reagents of thiols

Abstract: Abstract Sulfur–heteroatom bonds such as S–S and S–N are found in a variety of natural products and often play important roles in biological processes. Despite their widespread applications, the synthesis of sulfenamides, which feature S–N bonds that may be cleaved under mild conditions, remains underdeveloped. Here, we report a method for synthesis of N -acyl sulfenamides via copper-catalyzed nitrene-mediated S -amidation reaction of thiols with dioxazolones. This method is efficient, convenient, and broadly applicable. Moreover, the resulting N -acetyl sulfenamides are highly effective S -sulfenylation reagents for the synthesis of unsymmetrical disulfides under mild conditions. The S -sulfenylation protocol enables facile access to sterically demanding disulfides that are difficult to synthesize by other means.

Bioconjugation via Hetero-Selective Clamping of Two Different Amines with ortho-Phthalaldehyde.

Abstract: Amino groups are common in both natural and synthetic compounds and offer a very attractive class of endogenous handles for bioconjugation. However, the ability to differentiate two types of amino groups and join them with high hetero-selectivity and efficiency in a complex setting remains elusive. Herein, we report a new method for bioconjugation via one-pot chemoselective clamping of two different amine nucleophiles using a simple ortho-phthalaldehyde (OPA) reagent. Various α-amino acids, aryl amines, and secondary amines can be crosslinked to the ε-amino side chain of lysine on peptides or proteins with high efficiency and hetero-selectivity. This method offers a simple and powerful means to crosslink small molecule drugs, imaging probes, peptides, proteins, carbohydrates, and even virus particles without any pre-functionalization.

Construction of Complex Macromulticyclic Peptides via Stitching with Formaldehyde and Guanidine.

Abstract: There is a growing interest in constructing multicyclic peptide structures to expand the chemical space of peptides. Conventional strategies for constructing large peptide structures are limited by the typical reliance on the inflexible coupling between premade templates equipped with fixed reactive handles and peptide substrates via cysteine anchors. Herein, we report the development of a facile three-component condensation reaction of primary alkyl amine, formaldehyde, and guanidine for construction of complex macromulticyclic peptides with novel topologies via lysine anchors. Moreover, the reaction sequences can be orchestrated in different anchor combinations and spatial arrangements to generate various macrocyclic structures crosslinked by distinct fused tetrahydrotriazine linkages. The macrocyclization reactions are selective, efficient, versatile, and workable in both organic and aqueous media. Thus, the condensation reaction provides a smart tool for stitching native peptides in situ using simple methylene threads and guanidine joints in a flexible and programmable manner.

Ruthenium-Catalyzed Pyridine-Directed Aryl C-H Glycosylation with Glycosyl Chlorides.

Abstract: Metal-catalyzed C-H glycosylation reactions with glycosyl chloride donors have emerged as a useful strategy for the synthesis of C-glycosides. Previously, palladium and nickel complexes were reported to catalyze C-H glycosylation reactions using amide-linked bidentate auxiliaries. Herein, a ruthenium-catalyzed ortho C-H glycosylation reaction of arenes with various glycosyl chloride donors using a monodentate pyridine directing group is developed. Preliminary mechanistic studies indicated that two-electron oxidative addition and reductive elimination of ruthenocycle intermediate led to the glycosylation products.

Laboratory investigation on quantitative effect of ladle filler sands on the cleanliness of a bearing steel

Abstract: Laboratory experiments were performed using two kinds of heating furnaces to investigate the quantitative effect of ladle filler sands (LFS) on the cleanliness of a bearing steel at the casting start of the first heat and non-first heats of a casting sequence. After the direct addition of LFS into the molten steel, which was the condition of the first heat, inclusions in steel changed from MgO · Al2O3 to Al2O3. As the LFS/steel ratio increased from 0 to 1:600, the number density of inclusions significantly increased from 5.3 #/mm2 to 14.5 #/mm2 and the area fraction of inclusions sharply increased from 7.8 ppm to 60.6 ppm, inducing the sharp increase of T.O to 16.1 ppm. After the reaction between the LFS contained tundish covering powder (TCP) and the molten steel, inclusions in steel were separated into a MgO-Al2O3 system and a CaO-Al2O3(-MgO) system. With the increase of LFS/TCP ratio to 1:12, the average MgO content in inclusions decreased to 19.1 wt% while the Al2O3 content increased to 77.0 wt%, meanwhile, the T.O content increased to 6.0 ppm and the [Al] content decreased to 50 ppm. Based on experimental results and the thermodynamic analysis, the detrimental effect of LFS on the steel cleanliness of non-first heats was much slighter than that of the first heat owing to the use of high-basicity TCP. Accordingly, more efforts should be made to prevent the LFS charging into the molten steel at the casting start of the first heat of a casting sequence during the industrial production.

Hypervalent-iodine Promoted Selective Cleavage of C(sp3)-C(sp3) Bonds in Ethers

Abstract: A visible-light-promoted and radical-mediated strategy for the site-specific cleavage of C(sp3)-C(sp3) bonds in ethers is reported. Different cyclic and linear alkyl ethers are converted into benzoylated acetals and aldehydes or...

Introduction to ‘Synthesis and chemical biology of macrocycles’

Abstract: Gong Chen, Monika Raj and Andrei Yudin introduce the RSC Chemical Biology themed collection on the ‘Synthesis and chemical biology of macrocycles’.

Effect of lining refractory and high-basicity slag on non-metallic inclusions in a high carbon Al-killed steel

Abstract: Laboratory experiments on the effect of lining refractory and high-basicity slag on non-metallic inclusions in a high carbon Al-killed steel were carried out. Alumina inclusions in the steel could hardly be affected by the Al2O3 refractory, however, would be transformed into MgO · Al2O3 when the MgO refractory was used. After the steel-slag-MgO lining-inclusion reaction, the high-basicity slag was saturated with MgO due to the dissolution of MgO from the refractory into the slag, meanwhile, original Al2O3 inclusions were transformed into MgO via MgO · Al2O3, regardless of the slag basicity. After the steel-slag-Al2O3 lining-inclusion reaction, the CaO/Al2O3 ratio of slag decreased significantly due to the dissolution of Al2O3 refractory into the slag, resulting in the slight increase of the magnesium content in steel and the transformation of Al2O3 inclusions into MgO · Al2O3. The reduction of the MgO in the lining refractory and top slag by the dissolved aluminum ([Al]) in molten steel occurred independently, and a higher CaO/Al2O3 ratio of slag would result in a higher activity of MgO, which was beneficial for the reduction of MgO. The CaO in the slag was hardly reduced by the [Al] in the molten steel, thus, it was proposed that CaO-Al2O3 type inclusions could hardly be generated from the steel-slag reaction during the production of high carbon Al-killed steels.