New Natural Ring Octapeptide Clausenain Design And Synthesis Of B

Clausenain B is a new cyclopeptide isolated from Clausena anisum-olens, Clausenain B contains eight natural amino acid, contain four Phe, two Leu, one Ser, one Gly. The cyclic peptide has the same amino acid unit highly repetitive structural features, which is less common in nature.It’s almost unable to make further study of the structure to Clausenain B, not only because there is few content contained in nature, but also due to it’s repeating units of amino acids which lead to heavely overlapping NMR spectra. In the mean while, the lack of natural content limits further study to its biological activity. To solve those problems in the study of Clausenain B, we get Clausenain B by total synthesis and make a lot further study to its structure.By inverse synthetic analysis, this paper selected many differents cyclization points to synthesis a cyclic octapeptide compound that has an order of [-Phe1-Ser-Leul-Phe2-Phe4-Gly-Leu2-Phe3-]. By compared with the’H NMR and13C NMR spectra of natural cyclic octapeptide, Clausenain B, it is confirmed those two compounds share the same structure, this result has been confirmed again in further2D NMR experiments.Through in-depth analysis of the two NOE experimental data, we draw the following conclusions:First, constitutes the connection of the two amino acid take the following order:[-Phel-Ser-Leu1-Phe2-Phe4-Gly-Leu2-Phe3-]; Second, all of the amino acids has the structure of L configuration expect Gly. The cyclic peptide can offer multiple cyclization, we carry out some study in order to get the optimized cyclization site.This paper based on the characteristics of the compounds, selected four inverse synthetic analysis different cyclization sites:a, b, c, d (Figure2.2), drawn through the experimental study where a, b, d three sites cyclization yields were47.9%,20.1%,37.5%, The total yield were5.9%,1.5%and5.5%. This paper also introduces the selection for the classification of the cyclic peptide, cyclization sites, the choice of the cyclization reagents, liquid phase synthesis of cyclic peptides and solid-phase synthesis, and the nature of cyclic peptide.