Enantioselective synthesis of gabapentin analogues via organocatalytic asymmetric Michael addition of α-branched aldehydes to ß-nitroacrylates.

Michael addition reaction of α-branched aldehydes to ß-nitroacrylates was successfully carried out by using a mixed catalyst consisting of a primary amino acid, L-phenylalanine, and its lithium salt to give ß-formyl-ß'-nitroesters having a quaternary carbon centre in good yields (up to 85%) with high enantioselectivity (up to 98% ee). By using benzyl ß-nitroacrylates as Michael acceptors, the obtained ß-formyl-ß'-nitroesters were converted into various 4,4-disubstituted pyrrolidine-3-carboxylic acids including analogues of gabapentin (Neurotin(®)) in one step from the Michael adducts in high yields.

One-pot asymmetric synthesis of γ-nitroaldehydes from aldehydes and nitroalkanes through a catalytic tandem reaction using an amino acid lithium salt.

One-pot asymmetric synthesis of γ-nitroaldehydes from aldehydes and nitroalkanes was achieved by a catalytic tandem reaction using a primary amino acid lithium salt, O-tert-butyldiphenylsilyl l-tyrosine lithium salt, as a catalyst. Various aryl, alkenyl, and alkyl aldehydes were converted into γ-nitroaldehydes via in situ generation of nitroalkenes.

Defensive effects of human intestinal antimicrobial peptides against infectious diseases caused by Vibrio mimicus and V. vulnificus.

Of human pathogenic Vibrio species, V. mimicus causes gastroenteritis whereas V. vulnificus causes fatal septicemia after consumption of contaminated seafood. These two pathogens produce hemolytic toxins termed V. mimicus hemolysin (VMH) and V. vulnificus hemolysin (VVH), respectively. These toxins elicit the cytolysis of various eukaryotic cells, as well as erythrocytes. The human intestine secretes cationic antimicrobial peptides (AMPs) to prevent infectious diseases. Paneth cells in the small intestine secrete α-defensin 5 (HD-5) and epithelial cells in the large intestine produce LL-37. In the present study, we examined the bactericidal activities of AMPs against V. mimicus and V. vulnificus. Although HD-5 showed no bactericidal activity, LL-37 revealed significant activity against both Vibrio species, suggesting that neither V. mimicus nor V. vulnificus can multiply in the large intestine. We also tested whether AMPs had the ability to inactivate the hemolytic toxins. Only HD-5 was found to inactivate VMH, but not VVH, in a dose-dependent manner through the direct binding to VMH. Therefore, it is considered that V. mimicus cannot penetrate the small intestinal epithelium because the cytolytic action of VMH is inactivated by HD-5.