The Regiocontrollable Enantioselective Synthesis of Chiral Trifluoromethyl-Containing Spiro-Pyrrolidine-Pyrazolone Compounds via Amino-Regulated 1,3-Proton Migration Reaction.

An amino-controlled regiodivergent asymmetric synthesis of CF3-containing spiro-pyrrolidine-pyrazolone compounds is described. With alkaloid-derived squaramide as catalyst, the 1,3-dipolar cycloaddition of α,ß-unsaturated pyrazolone with diethyl 2-((2,2,2-trifluoroethyl)imino) malonate offered adducts in excellent yields, dr, and ee. While the cyclohexanediamine-derived squaramide was employed, the reaction afforded a series of structure isomers through a switched umpolung reaction.

The introduction of L-phenylalanine into antimicrobial peptide protonectin enhances the selective antibacterial activity of its derivative phe-Prt against Gram-positive bacteria.

Protonectin was a typical amphiphilic antimicrobial peptide with potent antimicrobial activity against Gram-positive and Gram-negative bacteria. In the present study, when its eleventh amino acid in the sequence was substituted by phenylalanine, the analog named phe-Prt showed potent antimicrobial activity against Gram-positive bacteria, but no antimicrobial activity against Gram-negative bacteria, indicating a significant selectivity between Gram-positive bacteria and Gram-negative bacteria. However, when Gram-negative bacteria were incubated with EDTA, the bacteria were susceptible to phe-Prt. Next, the binding effect of phe-Prt with LPS was determined. Our result showed that LPS could hamper the bactericidal activity of phe-Prt against Gram-positive bacteria. The result of zeta potential assay further confirmed the binding effect of phe-Prt with LPS for it could neutralize the surface charge of E. coli and LPS. Then, the effect of phe-Prt on the integrity of outer membrane of Gram-negative bacteria was determined. Our results showed that phe-Prt had a much weaker disturbance to the outer membrane of Gram-negative bacteria than the parent peptide protonectin. In summary, the introduction of L-phenylalanine into the sequence of antimicrobial peptide protonectin made phe-Prt show significant selectivity against Gram-positive bacteria, which could partly be attributed to the delay effect of LPS for phe-Prt to access to cell membrane. Although further study is still needed to clarify the exact mechanism of selectivity, the present study provided a strategy to develop antimicrobial peptides with selectivity toward Gram-positive and Gram-negative bacteria.

The catalytic asymmetric synthesis of CF3-containing spiro-oxindole-pyrrolidine-pyrazolone compounds through squaramide-catalyzed 1,3-dipolar cycloaddition.

Pharmaceutically important compounds were synthesized through the organocatalytic 1,3-dipolar cycloaddition reaction. In the presence of a cinchonine-derived squaramide catalyst, the cycloaddition of N-2,2,2-trifluoroethylisatin ketimines with α,ß-unsaturated pyrazolones gave a spiro-pyrrolidine-linked oxindole and pyrazolone compound bearing four consecutive stereocenters and two vicinal spiroquaternary chiral centers, in excellent yields and stereoselectivities.

The asymmetric construction of CF3-containing spiro-thiazolone-pyrrolidine compounds via [3 + 2] cycloaddition.

The first organocatalytic method for the asymmetric construction of CF3-containing spiro-thiazolone-pyrrolidine compounds has been developed. This is one of the very few methods to reach spiro-thiazolones, and afforded the products in excellent yields and stereoselectivities catalysed by only 1 mol% cinchona alkaloid-derived catalyst.