ABSTRACT
A full account on the synthesis of the antibiotic natural product biphenomycin B and several derivatives is reported, which employs a Suzuki coupling reaction of a free carboxylic acid and macrolactam formation as key transformations. Liberal exchange of the central amino acid was demonstrated. This procedure gave derivatives to study the influence of the polar side chain of the central amino acids on translation inhibition.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Peptides, Cyclic/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Escherichia coli/metabolism , Peptides, Cyclic/chemistry , Peptides, Cyclic/pharmacology , Protein Biosynthesis/drug effects , Ribosomes/drug effectsABSTRACT
A total synthesis of the biaryl antibiotic biphenomycin B is reported which makes use of three independent building blocks (key steps were a clean Suzuki-Miyaura coupling of a free acid iodide, a novel 4-hydroxyornithine synthesis, and a high-yielding macrolactamization); a practical deprotection protocol allowed isolation of the target compound with excellent recovery and purity.
Subject(s)
Peptides, Cyclic/chemical synthesis , Molecular Structure , Peptides, Cyclic/chemistry , StereoisomerismABSTRACT
In the course of studies directed toward the discovery of novel scaffolds for medicinal application, we synthesized a series of 3-substituted indolizine-1-carbonitrile derivatives. Some of them displayed activity against MPtpA/MPtpB phosphatases which are involved in infectious diseases. We report here the solid-phase synthesis and antiphosphatase activity of a series of indolizines.