Studies On Chemical Constituents Of Psammosilene Tunicoides W. C. Wu Et C. Y. Wu

Psammosilene tunicoides W. C. Wu et. C. Y. Wu, a monotype genus plant of Caryophyllaceace family, is a well-known medicinal herb used as anodyne and haemastatic agent in southwest China. This dissertaion describes the chemical constituents and bioactivity study of P. tunicoides. In addition, some of compounds from the titled species were modified and tested for their bioactivities.1. The chemical constituents of Psammosilene tunicoides80 chemical constituents, including cyclic peptides (1~11), triterpenoid saponins (12~29), carbolines (30~35), maltol glycosides (36~51), lignans (52~58), and other compounds (59~80) were isolatied from P. tunicoides. The structures of 79 compounds were elucidated on the basis of spectroscopic studies. 44 compouds were indentified as new compouds. Compound 1 (tunicyclin A) is the first tricyclic cyclopeptide with a unique tricyclic ring cyclopeptide skeleton from higher plant. The structure of a diketopyrrolo[1,2-a]pyrazine in compound 1 (tunicyclin A) is totally new in the peptides area. Furthermore, both compound 4 (tunicyclin B) and compound 10 (tunicyclin I) contain unusualα,β-dehydrotryptophan (ΔZ-Trp) residues,previously reported only from marine sponge and bacteria.2. The conformation analysis of tunicyclin E (5) and the intramolecular catalysis of cis/trans isomerization of peptidyl-prolyl bondCompound 5 (tunicyclin E) exists in two conformations (5a, trans; 5b, cis) in solution that derive from restricted rotation of the Ser7-Pro1 peptide bond, while only trans Ser7-Pro1 conformation is found in crystal state. To explore the molecular basis of two conformations of 5 in solution and their interconversion mechanism, X-ray diffraction, NMR experiments, and theoretical calculations were performed. The kinetics study revealed an unexpected rate enhancement of peptidyl-prolyl bond isomerization which is proposed an intramolecular catalysis mechanism and solvent effect. Also, several unusual pseudo turns are first characterized in trans conformation.3. The modification of two triterpenoid saponins and a cyclic peptideSix derivatives of two triterpenoid saponins (compounds 12 and 16) were obtained by chemical modification. Two of them showed potent immunological adjuvant activities. In addition, we also modified a cyclic peptide tunicyclin E (5) to screen for HDACs inhibitors.4. One-step biomimetic synthesis of tunicyclin A (1) Further study disclosed that tunicyclin A (1) could be obtained from tunicyclin E (5) by photosensitized oxidation reaction. One reactive mechanism due to oxidative free-radical addion was proposed to interpret the synthesis from tunicyclin E to tunicyclin A. It is also the plausible biogenetic pathway for tunicyclin A.5. Bioactivities assay of cyclic peptides and triterpenoid saponinsA cyclic peptide tunicyclin D (2) showed broad-spectrum potent antifungal activity. In addition, the total saponin of P. tunicoides and their fractions were tested for inhibitory activity against LPS-induced NO production in RAW 264.7 macrophage and against NF-κB activities induced by TNF-α. The results showed the total saponin had anti-inflammatory effect.6. Review the anti-inflammation mechanism of chemical constituents of TCM...