10.1016/S0040-4039(00)84780-2
The research focuses on the stereoselective synthesis of the C-15 to C-20 segment of rifamycin-S, specifically targeting the construction of 5-substituted 2-methyl-2Z,4E-pentadienoic acid. The purpose of this study was to develop a new and stereoselective method for the synthesis of this key compound, which is part of the ansa chain of rifamycin-S. The researchers achieved this by using a series of chemical reactions starting with the alkylation of ethyl 2-selenophenyl propionate with substituted allylic chloride in the presence of LDA, followed by hydrolysis, iodolactonization, oxidative elimination of the selenophenyl group, and finally, treatment with zinc in refluxing ethanol to yield the desired dienoic acid. The study concluded that the methodology was successful in constructing the target molecule with the correct stereochemistry and could be valuable for a variety of synthetic approaches, including the construction of the ansa chain 2 of rifamycin-S.
10.1021/jm00181a015
The study investigates the synthesis and biological activity of two compounds, XIIIa and XIIIb, designed to inhibit ribosomal peptidyltransferase, an enzyme crucial for peptide bond formation during protein synthesis. The researchers used a series of chemical reactions involving starting materials like p-(2-amino-ethyl)adenosine (Ia) and methyl orthoacetate (II) to synthesize the target compounds. The synthesis process included steps such as cyclization, hydrolysis, and coupling reactions to form intermediates like III, VI, and XIa/b, ultimately leading to XIIIa and XIIIb. These compounds were tested for their ability to inhibit the puromycin reaction catalyzed by ribosomes. The study found that XIIIb, with a longer alkyl chain, was a more effective inhibitor than XIIIa, suggesting that the length of the alkyl chain significantly impacts the inhibitory activity. The results indicate that these compounds simulate the 3’ terminal of aminoacyl-tRNA rather than being transition state analogues of the enzyme-catalyzed reaction, providing insights into the mechanism of action of peptidyltransferase.
