Peixue Cao

Synthesis and anti-hepatitis B virus activities of Matijing-Su derivatives.

A series of derivatives of Matijing-Su (MTS, N-(N-benzoyl-L-phenylalanyl)-O-acetyl-L-phenylalanol) was synthesized and evaluated for their anti-hepatitis B virus (HBV) activities in 2.2.15 cells. The IC(50) of compounds 9c (1.40 microM), 9g (2.33 microM) and 9n (2.36 microM), etc. and the selective index of 9n (45.93) of the inhibition on the replication of HBV DNA were higher than those of the positive control lamivudine [41.59, (IC(50): 82.42 microM)]. Compounds 11d, 12a and 12e also exhibited significant anti-HBV activities.

Synthesis and biological evaluation of Matijing-Su derivatives as potent anti-HBV agents.

A series of Matijing-Su (MTS, N-(N-benzoyl-l-phenylalanyl)-O-acetyl-L-phenylalanol) derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activity in 2.2.15 cells. The IC(50) of compounds 14a (0.71 μM), 13c (2.85 μM), 13b (4.37 μM), etc. and the selective index of 13g (161.01), 13c (90.45), 13a (85.09) etc. of the inhibition on the replication of HBV DNA were better than those of the positive control lamivudine (IC(50): 82.42 μM, SI: 41.59). Compounds 13o, 13p, and 16a also exhibited significant anti-HBV activity.

A novel iridoid from Torricellia angulata var intermedia

A new iridoid, named torricellate, was isolated from root bark of Torricellia angulata var intermedia, a Chinese folk medicinal plant used to treat bone fracture, tonsillitis and asthma. Its structure was elucidated by NMR, MS, IR and UV, and confirmed by X-ray diffraction studies.

Two new naturally occurring optical polyacetylene compounds from Torricellia angulata var intermedia and the determination of their absolute configurations

Four compounds were isolated from Torricellia angulata var intermedia (Harms.) Hu (Torricelliaceae), followed by formation of derivatives, which gave two new polyacetylene compounds 3 and 4 with respectively a chiral carbon center whose absolute configurations were determined unambiguously by the recently developed extended Moshers method. This is the first time to obtain natural polyacetylenes possessing a chiral hydroxyl group.

A new ecdysteroidal glycoside from Lepidogrammitis drymoglossoides (Bak.) Ching.

Lepidogrammitis drymoglossoides (Bak.) Ching is a medicinal plant that belongs to the family of Polypodiaceae. Previous phytochemical investigation on this genus had revealed the presence of flavonoids, sterols, and alkaloids. Here, further investigation on this medicinal plant led to the isolation of a new ecdysteroidal glycoside, ponasteroside B (1), along with a known steroidal compound, β-ecdysterone (2). The structure of 1 was determined on the basis of extensive spectroscopic analysis, including HR-MS and 1D and 2D NMR experiments, as well as a chemical hydrolysis study.

Synthesis and anti-tumor activity evaluation of Matijin-Su derivatives

A series of Matijin-Su (MTS, N-(N-benzoyl-l-phenylalanyl)-O-acetyl-l-phenylalanol) derivatives was synthesized and evaluated for their anti-tumor activities in hepatocellular carcinoma cells. The IC50 of compounds 1, 3, 4, 11, 13 were less than 20μM, and compound 1 and 3 showed an IC50 value of less than 9μM. Expansion inhibition could be found significantly in compound 1 and 3-treated human hepatoma cell HepG2 and PLC/PRF/5, while both compounds exhibit lower toxicity to human hepatocyte cell line L-02. Compound 1 and 3 could induce cell cycle arrest at G1/S phase. This may be attributed to increase level of intracellular reactive oxygen species (ROS). Up-regulation of p38 MAPK activity in responding the ROS stabilize p53 and activate p21 transcription, the critical regulatory in G1/S checkpoint. Observations in this study shed light on the potential of MTS derivatives compound 1 and 3 as novel suppressors to human liver cancer.

Process development of clinical anti-HBV drug Y101: identification and synthesis of novel impurities

Abstract Nine novel process impurities of N-[N-benzoyl-O-(2-dimethylaminoethyl)-l-tyrosyl]-l-phenylalaninol (Y101) observed during the laboratory optimization and later during its bulk synthesis are described in this article. The impurities were monitored by HPLC, and their structures were tentatively assigned on the basis of fragmentation patterns in LC−MS/MS and NMR spectroscopies. All of the impurities were synthesized, and their assigned constitutions were confirmed by co-injection in HPLC. In addition to the formation, synthesis, and characterization, the strategy for minimizing these impurities to a level accepted by the International Conference on Harmonisation (ICH) was also described.