1. Convergent Synthesis of Thioether Containing Peptides
Spyridon Mourtas, Christina Katakalou, Dimitrios Gatos, Kleomenis Barlos Molecules. 2020 Jan 5;25(1):218. doi: 10.3390/molecules25010218.
Thioether containing peptides were obtained following three synthetic routes. In route A, halo acids esterified on 2-chlorotrityl(Cltr) resin were reacted with N-fluorenylmethoxycarbonyl (Fmoc) aminothiols. These were either cleaved from the resin to the corresponding (Fmoc-aminothiol)carboxylic acids, which were used as key building blocks in solid phase peptide synthesis (SPPS), or the N-Fmoc group was deprotected and peptide chains were elongated by standard SPPS. The obtained N-Fmoc protected thioether containing peptides were then condensed either in solution, or on solid support, with the appropriate amino components of peptides. In route B, the thioether containing peptides were obtained by the reaction of N-Fmoc aminothiols with bromoacetylated peptides, which were synthesized on Cltr-resin, followed by removal of the N-Fmoc group and subsequent peptide elongation by standard SPPS. In route C, the thioether containing peptides were obtained by the condensation of a haloacylated peptide synthesized on Cltr-resin and a thiol-peptide synthesized either on 4-methoxytrityl(Mmt) or trityl(Trt) resin.
2. Parallel synthesis of 1,6-disubstituted-1,2,4-triazin-3-ones on solid-phase
Miao Hu, Wei Huang, Marc A Giulianotti, Richard A Houghten, Yongping Yu ACS Comb Sci. 2013 Jul 8;15(7):335-9. doi: 10.1021/co400064d. Epub 2013 Jun 13.
A parallel solid-phase synthesis of 1,6-disubstituted-1,2,4-triazin-3-ones from MBHA resin is described. The reduction of resin-bound nitrosamino acids provides hydrazines efficiently without affecting the amide bond. The trityl protected hydrazine is then reduced with borane, and cyclized with 1,1-carbonyldiimidazole. The desired products are cleaved from their solid support and obtained in good yield and purity. This methodology is of value for the rapid parallel preparation of these potentially bioactive molecules.
3. Solid-phase synthesis and bioactivity evaluation of cherimolacyclopeptide E
Yuka Yoshida, Minoru Inagaki, Yuichi Masuda J Pept Sci. 2021 Jun;27(6):e3308. doi: 10.1002/psc.3308. Epub 2021 Feb 15.
Cherimolacylopeptide E (1) is a cyclic hexapeptide isolated from the seeds of Annona cherimola. Peptide 1 reportedly exhibits potent cytotoxicity against KB cells (IC50 0.017 μM). To confirm the structure and bioactivity of 1, we conducted a total synthesis of its proposed structure. The synthesis was accomplished via solid-phase peptide elongation and macrocyclization by employing Fmoc/OAll-protected amino acids on 2-Cl-trityl resin. NMR analysis revealed that synthetic 1 exists in two conformations in pyridine-d5 . As the spectroscopic data of the major conformer of synthetic 1 were consistent with those of natural 1, the structure of cherimolacyclopeptide E was confirmed to be 1. However, our synthetic 1 exhibited low cytotoxicity against KB cells (IC50 > 100 μM). In contrast to previously-reported findings, our synthetic 1 exhibited little antibacterial activity against Escherichia coli.
