Avoiding Undesired Intramolecular Diketopiperazine Formation during Peptoid Chain Elongation Using a Microflow Reactor.

Avoiding undesired intramolecular reactions during desired intermolecular reactions is an important challenge in synthetic organic chemistry. We successfully avoided undesired intramolecular diketopiperazine formation during desired N-alkylation in the synthesis of peptoids using a microflow reactor. Fifteen peptoids were synthesized in good to high yields, and a cyclic peptoid was synthesized on the gram scale using the developed microflow approach.

Step-by-Step Protocol to Generate Hi-C Contact Maps Using the rfy_hic2 Pipeline.

The Hi-C method has emerged as an indispensable tool for analyzing the 3D organization of the genome, becoming increasingly accessible and frequently utilized in chromatin research. To effectively leverage 3D genomics data obtained through advanced technologies, it is crucial to understand what processes are undertaken and what aspects require special attention within the bioinformatics pipeline. This protocol aims to demystify the Hi-C data analysis process for field newcomers.

One-step syntheses of diaza-dioxa-fenestranes via the sequential (3 + 2) cycloadditions of linear precursors and their structural analyses.

Fenestranes, in which four rings share one carbon atom, have garnered much attention because of their flattened quaternary carbon centers. In addition, the rigid and nonplanar structures of heteroatom-containing fenestranes are attractive scaffolds for pharmaceutical applications. We report one-step syntheses of diaza-dioxa-fenestranes via the sequential (3 + 2) cycloadditions.

Effects of hypernatremia on the microglia.

Signs and symptoms of hypernatremia largely indicate central nervous system dysfunction. Acute hypernatremia can cause demyelinating lesions similar to that observed in osmotic demyelination syndrome (ODS). We have previously demonstrated that microglia accumulate in ODS lesions and minocycline protects against ODS by inhibiting microglial activation.

Effect of Brønsted Acids on the Activation of Mixed Anhydride/Mixed Carbonic Anhydride and C-Terminal-Free N-Methylated Peptide Synthesis in a Micro-Flow Reactor.

Amidations employing mixed (carbonic) anhydrides have long been favoured in peptide synthesis because of their cost-effectiveness and less waste generation. Despite their long history, no study has compared the effects of additives on the activation of mixed anhydrides and carbonic anhydrides. In this study, we investigated the amidation of mixed (carbonic) anhydride in the presence of a base and/or Brønsted acids.

Rapid generation of 2-(halomethyl)-5-phenylfuran and nucleophilic addition in a microflow reactor.

2,5-Disubstituted furans are frequently found in pharmaceuticals and bioactive natural products. Nucleophilic substitution reactions on the carbon atom adjacent to the furan ring are useful for producing various furan derivatives. However, the formation of 5-substituted 2-halomethylfuran and the subsequent nucleophilic substitution reactions are often limited by severe undesired reactions caused by the highly reactive halomethylfurans.

Microflow, Sequential Coupling and Cyclization Approach for Synthesis of Cyclic Phosphotriesters from PCl.

An approach for the synthesis of cyclic phosphotriesters with various ring sizes (5- to 8-membered rings) from phosphorus trichloride and diols was developed. The major challenge in developing this approach is the suppression of the undesired reactions caused by substrates containing multiple highly reactive sites. These undesired reactions were successfully suppressed by microflow technology, which can precisely control the reaction time and temperature.

Correction: Micro-flow heteroatom alkylation TfOH-mediated rapid generation of carbocations and subsequent nucleophile addition.

Correction for 'Micro-flow heteroatom alkylation TfOH-mediated rapid generation of carbocations and subsequent nucleophile addition' by Yuma Matsuura , , 2024, https://doi.org/10.1039/D3CC06308A.

Micro-flow heteroatom alkylation TfOH-mediated rapid generation of carbocations and subsequent nucleophile addition.

A rapid nucleophilic substitution reaction was developed using carbocations generated from diarylmethanol and trifluoromethanesulfonic acid. Undesired reactions caused by the carbocations were suppressed, presumably due to the rapid and uniform generation of carbocations and the subsequent rapid and uniform distribution of nucleophiles by the micro-flow technology.

Microflow Synthesis of Unsymmetrical -Phosphonates via Sequential and Direct Substitution of Chlorine Atoms in Phosphorus Trichloride with Alkoxy Groups.

Unsymmetrical -phosphonates were synthesized by a rapid (<15 s) and mild (20 °C) process in a microflow reactor as the first example of the sequential direct substitution of the chlorine atoms in PCl with alkoxyl/aryloxy groups using equivalent amounts of PCl and alcohols. The optimal base concentration differed in each step, presumably attributed to differences in the Brønsted basicity of the electrophilic intermediates. Phosphite hydrolysis was observed, and the structure-hydrolysis relationship was quantitatively evaluated.

One-Flow Synthesis of Substituted Indoles via Sequential 1,2-Addition/Nucleophilic Substitution of Indolyl-3-Carbaldehydes.

Substituted indoles are important as drugs. A number of valuable indoles have been synthesized via nucleophilic substitution at the 3'-position of indoles. However, the preparation of an indolylmethyl electrophile containing a tertiary carbon at the 3'-position and its subsequent nucleophilic substitution are challenging owing to the instability of the electrophile.

Rapid and column-chromatography-free peptide chain elongation a one-flow, three-component coupling approach.

Short peptides are extremely important as drugs and building blocks for the syntheses of longer peptides. Both solid- and liquid-phase peptide syntheses suffer from a large number of synthetic steps, high cost, and/or tedious purification. Here, we developed a rapid, mild, inexpensive, and column-chromatography-free peptide chain elongation a one-flow, three-component coupling (3CC) approach that is the first to use α-amino acid -carboxy anhydrides (α-NCAs) both as electrophiles and nucleophiles.

One-Flow Syntheses of Unsymmetrical Sulfamides and -Substituted Sulfamate Esters.

We developed one-flow syntheses of unsymmetrical sulfamides and -substituted sulfamate esters by changing a nucleophile and a tertiary amine from inexpensive and commercially available chlorosulfonic acid. In the synthesis of -substituted sulfamate esters, unexpected symmetrical sulfite formation was suppressed by changing the tertiary amine. The effect of tertiary amines was proposed using linear regression.

Continuous-/Micro-Flow Reactions Using Highly Electrophilic PCl and POCl.

PCl and POCl are the most important sources of phosphorus-containing compounds. They are also used for large-scale industrial productions. However, chemical reactions using the highly reactive PCl and POCl tend to result in overreactions.

Peptide Cyclization by the Use of Acylammonium Species.

Although cyclic peptides have become increasingly important as drugs, the most conventional peptide cyclization method using moderately active coupling agents suffers from a lot of waste and high cost as well as long reaction times and burdensome purification. Herein, we report an unconventional approach to peptide cyclization that uses acylammonium species generated from inexpensive and less wasteful Me NBn and ClCO i-Pr. Using this approach, we observed the desired rapid activation of the C-terminus of cyclization precursors by an acylammonium ion for rapid and epimerization/dimerization-free cyclization of synthetically challenging peptides, including a difficult cyclization involving N-methyl amide bond formation.

Verification of preparations of (1H-indol-3-yl)methyl electrophiles and development of their microflow rapid generation and substitution.

Although highly reactive (1H-indol-3-yl)methyl electrophiles such as (1H-indol-3-yl)methyl halides are potential precursors for the synthesis of various indole derivatives, some researchers have reported difficulties in their preparation due to concomitant undesired dimerization/oligomerization. Nevertheless, there have been some reports on the preparation of (1H-indol-3-yl)methyl halides. To resolve this contradiction, all the previously reported preparations of (1H-indol-3-yl)methyl halides were examined.

Complementary Effect of Transcutaneous Cervical Stimulation by Interferential Current on Functional Dysphonia.

Objectives: Functional dysphonia (FD) varies in terms of vocal behavior and treatment efficacy. So-called hypofunctional dysphonia is characterized by insufficient subglottal pressure which causes a lack of driving power needed to vibrate the vocal folds leading to weak voice or aphonia in severe cases. While voice therapy is the initial treatment, some patients fail to respond to it.