Roodbeen, Renee published the artcileMicrowave Heating in the Solid-Phase Synthesis of N-Methylated Peptides: When Is Room Temperature Better?, Name: (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is European Journal of Organic Chemistry (2012), 2012(36), 7106-7111, database is CAplus.
The N-methylation of backbone amides in synthetic peptides is an important method for improving properties such as bioavailability, stability, as well as structural preferences, and is thus an attractive design strategy. However, the synthesis of N-methylated peptides can be challenging as the nucleophile in the acylation step is a sterically hindered secondary amine. In this study, the authors have systematically evaluated the use of microwave heating, different coupling conditions and the role of steric effects on coupling yields. First, the coupling reagent providing the highest yields was identified by a series of test N-acylation reactions on a selected peptide sequence. Secondly, a comparison of the coupling temperature, i.e., room temperature vs. microwave heating, with the optimal coupling reagent was performed. Finally, under the optimal conditions, a comprehensive study employing a set of sterically hindered N-methylated amino acids was conducted. Interestingly, incorporation of Fmoc-Arg(Pbf)-OH proceeded with higher yields at room temperature than at elevated temperature as a result of intramol. Arg lactam formation, which competes with intermol. amide bond formation. Fmoc-Arg(Boc)2-OH provided even lower coupling yields, due to the complete formation of the Arg lactam product. These studies have led to a robust, rapid, easy and high-yielding microwave-assisted method using COMU for the incorporation of Fmoc amino acids into challenging, sterically hindered N-methylated amino acid residues in a peptide sequence without the use of harsh reagents.
European Journal of Organic Chemistry published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C25H23NO4, Name: (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid.
Referemce:
https://en.wikipedia.org/wiki/Ether,
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