Biomimetic Peptide Catalytic Bond-Forming Utilizing a Mild Brønsted Acid.

Since the global peptide drug market demand has been predicted to increase, highly efficient and inexpensive mass scale peptides are required. However, the production process raises questions about the cost of energy input, scale-up production, raw materials, and solvents treatment. This paper introduces 2 methods for the 2-4 mer oligopeptides bond formation for batch reaction utilizing 50-100 mol% of a mild Brønsted acid under the mild condition. One of the methods has been capably adapted to flow synthesis at room temperature using organic solvents with boiling points below 100 °C. The method applies the tert-butoxycarbonyl amino methoxy group, forming the desired dipeptide without solvent at mild temperatures. Furthermore, the conversion of the carboxylic acid leaving the group to phenyl ester promotes peptide bond formation, and the reaction were applied to di, tri, and tetrapeptide bond formation in excellent yield without notable racemization at ambient temperature (up to >99 % yield and 99 : 1 dr). Finally, this study proposes this new production method to overcome the limited scale-up production by reaction device scale: liquid phase biomimetic catalytic peptide flow synthesis utilizing a mild Brønsted acid.

Process Catalyst Mass Efficiency by Using Proline Tetrazole Column-Flow System.

Generally, organocatalysts are not decomposed during chemical transformation, which is different from traditional metal catalysts. To improve catalytic processes efficiency, various studies have been applied to flow synthesis for organocatalysis. Furthermore, many immobilized organocatalysts have been used for heterogeneous flow synthesis, which requires huge amounts of immobilized catalyst and requires several steps to prepare. We took advantage of organocatalysts with low-polarity organic solvent and developed a flow system through a packed-bed column with simply proline tetrazole (5-(2-pyrrolidinyl)-1H-tetrazole) for heterogeneous organocatalytic synthesis. Under ambient temperature, this heterogeneous organocatalyst continuous flow-column system with ketones as a donor provides aldol, Mannich, and o-nitroso aldol reactions in up to quantitative yields with excellent enantio- and chemoselectivity values. Our heterogeneous-flow synthesis provides extremely low process catalyst mass efficiency and continuous production without changing the packed-bed catalyst column.

Asymmetric Aldol Synthesis: Choice of Organocatalyst and Conditions.

This is the first report of a successful asymmetric aldol reaction of acetone and 4-nitrobenzaldehyde catalyzed by only 0.01 mol % of proline tetrazole (5-pyrrolidin-2-yltetrazole). Amazingly, 3 mol % of water as an additive has significantly improved the efficiency of the aldol reaction in terms of yield and enantioselectivity, up to a 0.1-mol-scale production (up to 99 % isolated yield, 84 % ee).

Continuous flow of nitroso Diels-Alder reaction.

Our flow reaction systems have provided quantitative yields of nitroso Diels-Alder products with no byproducts in cases of cyclic dienes without temperature and pressure controls. Additionally, the reaction times were significantly shortened by using homogeneous catalyst (CuCl) or heterogeneous reagent (MnO2) in comparison with batch reaction.

Detection of calprotectin and apoptotic activity in the colon of marmosets with chronic diarrhea.

The common marmoset (Callithrix jacchus) is used as a non-human primate laboratory animal. Marmoset wasting syndrome (MWS) is a disease endemic to captive colonies, and the pathogenesis is unclear. In the present study, marmosets with chronic bloody high-viscosity diarrhea, which is a contributing factor to MWS, were evaluated, and inflammation in the colon was found. Calprotectin is a surrogate marker of intestinal inflammation and induces apoptosis. Marmosets with chronic diarrhea exhibited higher levels of fecal calprotectin. Histochemical analyses showed high expression of calprotectin in the extravascular neutrophils and apoptosis in the chronic colitis lesions. No internal microbiological diseases were identified. Although the cause of chronic colitis was not identified, the marmoset could be a useful model of inflammatory bowel disease.

Simple multilevel halftoning excelled in gradation reproducibility.

A simple multilevel halftoning method, which is based on the conventional error diffusion method and realizes halftoning excelled in the distribution of dots, is proposed. The proposed method consists of three steps, e.g., the image decomposition, the generation of binary halftone images by the error diffusion, and the synthesis of a multilevel halftone image, and each step does not require a complicated algorithm. The effectiveness of the proposed method is indicated by applying it to three- and four-level halftoning of gray-tone and natural images.