10.1016/j.bmcl.2010.10.122
The research focuses on the development of novel gratisin (GR) derivatives with high antimicrobial activity and low hemolytic activity. The study investigates the impact of substituting each constituent amino acid residue of GR with alanine (Ala) and identifies that modifications at the Pro5,5 residues significantly influence both antibiotic and hemolytic activities. Specifically, replacing Pro residues at positions 5 and 5 with cationic amino acids like lysine (Lys) and arginine (Arg) enhances antibiotic activity while reducing toxicity to human blood cells. The researchers synthesized various GR analogues using Boc-solid phase peptide synthesis and characterized their structures and biological activities. Key chemicals involved in the synthesis include Boc-amino acids, BOP (benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate), HOBt (1-hydroxybenzotriazole), NEt3 (triethylamine), and thioanisole. The study also utilized reagents such as acetic acid and trifluoroacetic acid (TFA) for cyclization and deprotection steps. The findings suggest that these modified GR derivatives could serve as potential drug candidates to combat multidrug-resistant bacteria while minimizing adverse effects on human cells.
10.1021/jo025889b
The research presents a study on the synthesis of cyclic peptidomimetics from aldol building blocks, aiming to create selective small molecules for disease treatment. The researchers used aldol products with allyl-protected hydroxy groups, which were converted to amino alcohols through Curtius rearrangement. These amino alcohols were then combined with carboxylic acids to form amides, and ring-closing metathesis was employed to produce 12-membered lactams as mixtures of E/Z-isomers. Benzotriazole-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) was used as a coupling reagent for the formation of amides from carboxylic acids and amines. The process was also adapted to solid-phase synthesis, resulting in macrolactams via cyclorelease. The solution conformation of a pair of E/Z-isomers was determined using ROESY spectroscopy. The reactants included various aldol products, amino alcohols, carboxylic acids, and the Grubbs catalyst for ring-closing metathesis. Analyses used in the study comprised NMR spectroscopy for structural determination and ATR-FT-IR spectroscopy for monitoring the formation of intermediates on the resin.
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