ABSTRACT
Despite the remarkable developments of the Ugi reaction and its variants, the use of ammonia in the Ugi reaction has long been recognized as impractical and unsuccessful. Indeed, the ammonia-Ugi reaction often requires harsh reaction conditions, such as heating and microwave irradiation, and competes with the Passerini reaction, thereby resulting in low yields. This study describes a robust and practical ammonia-Ugi reaction protocol. Using originally prepared ammonium carboxylates in trifluoroethanol, the ammonia-Ugi reaction proceeded at room temperature in high yields and showed a broad substrate scope, thus synthesizing a variety of α,α-disubstituted amino acid derivatives, including unnatural dipeptides. The reaction required no condensing agents and proceeded without racemization of the chiral stereocenter of α-amino acids. Furthermore, using this protocol, we quickly synthesized a novel dipeptide, D-Leu-Aic-NH-CH2Ph(p-F), which exhibited a potent inhibitory activity against α-chymotrypsin with a Ki value of 0.091 µM.
Subject(s)
Amino Acids , Ammonia , Dipeptides , Dipeptides/chemistry , Dipeptides/chemical synthesis , Ammonia/chemistry , Amino Acids/chemistry , Amino Acids/chemical synthesis , Carboxylic Acids/chemistry , Carboxylic Acids/chemical synthesis , Ammonium Compounds/chemistry , Chymotrypsin/antagonists & inhibitors , Chymotrypsin/chemistry , Molecular Structure , Chemistry Techniques, SyntheticABSTRACT
Myxomycetes are multinucleate unicellular organisms. They form a Plasmodium that moves by protoplasmic flow and prey on microorganisms. When encountering intraspecifics, the plasmodium has the capacity for 'fusion', actively approaching and fusing its cells, or 'avoidance', altering its direction to avoid the other individual. This is an allorecognition ability. However, it remains unclear whether the range of allorecognition extends to other species, and its ecological significance is also obscure. Here, we conducted a quantitative evaluation of contact responses from closely related species of plasmodium to clarify the range of allorecognition behaviors in Myxomycetes. Behavioral assays demonstrated that allorecognition behaviors are specifically observed within individuals of the same species, indicating that these behaviors are a phenomenon unique to intraspecies interactions. Myxomycetes allorecognition is an extremely narrow and inward-focused behavior, suggesting a highly specialized mechanism.