Yun-Bao Ma

Synthesis and in vitro anti-hepatitis B virus activities of 4-aryl-6-chloro-quinolin-2-one and 5-aryl-7-chloro-1,4-benzodiazepine derivatives.

A series of 4-aryl-6-chloro-quinolin-2-ones and 5-aryl-7-chloro-1,4-benzodiazepine were synthesized and assayed for their in vitro anti-hepatitis B virus activities and cytotoxicities for the first time. Some of the tested compounds were active against HBsAg and HBeAg secretion in Hep G2.2.15 cells. Compound 5c showed IC(50) of 0.074 and 0.449 mM on HBsAg and HBeAg secretions, respectively, which were 10 times higher than that of its analog 4c and led to better selective index (SI) values (SI=23.2 and 3.4, respectively).

1-Aryl-tetrahydroisoquinoline analogs as active anti-HIV agents in vitro

A series of 1-aryl-6,7-dihydroxyl(methoxy)-1,2,3,4-tetrahydroisoquinolines (compounds 1-36) were synthesized via Pictet-Spengler cyclization. All the synthesized compounds were assayed for activities against HIV-1(IIIB) in C8166 cell cultures by MTT method for the first time. The results of the anti-HIV screening revealed that 6,7-dihydroxytetrahydroisoquinolines possessed higher selective index than 6,7-dimethoxyl analogs due to the significantly decreased cytotoxicities. Compounds 6, 24, and 36 showed potent anti-HIV activities with EC(50) values of 8.2, 4.6, and 5.3microM respectively, and the cytotoxicities (CC(50)) of these three compounds were 784.3, 727.3, and 687.3microM, which resulted in SI values larger than 95, 159, and 130 respectively.

Swerilactones A and B, Anti-HBV New Lactones from a Tradtional Chinese Herb: Swertia mileensis as a Treatment for Viral Hepatitis

Swerilactones A (1) and B (2), two novel lactones with an unprecedented 6/6/6/6/6 pentacyclic ring system, were isolated from the traditional Chinese herb of Swertia mileensis with activity against the hepatitis virus. Their structures and relative stereochemistry were elucidated based on spectroscopic methods and further confirmed by X-ray single crystal diffraction analysis. In vitro antihepatitis B virus (HBV) assay on Hep G 2.2.15 cell line showed that compound 1 inhibited HBsAg and HBeAg secretion with IC(50) values of 3.66 and 3.58 mM, respectively.

Anti-HBV agents. Part 1: Synthesis of alisol A derivatives: A new class of hepatitis B virus inhibitors

A series of alisol A derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activities and cytotoxicities in vitro. The preliminary investigation demonstrates that simple modifications of the parent structure of alisol A can produce a number of potentially important derivatives against HBV. The most active anti-HBV compound 6a showed high activities against the secretion of HBV surface antigen (IC(50)=0.024 mM), HBV e antigen (IC(50)=0.028 mM) and remarkable selective indices (SI(HBsAg)>108, SI(HBeAg)>93), which was selected for further evaluation as a novel HBV inhibitor.

Anti-HBV agents. Part 2: synthesis and in vitro anti-hepatitis B virus activities of alisol A derivatives.

Chemical modifications were performed on hydroxyl groups at C-11,23,24,25 positions and C-13(17) double bond of alisol A for structure-activity relationship study. Forty-one derivatives of alisol A were synthesized and assayed for their in vitro anti-hepatitis B virus (HBV) activities and cytotoxicities. Of them, 14 compounds were active against HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) secretion in HepG 2.2.15 cells, and the most promising compound 25 exhibited high activities against secretion of HBsAg (IC(50)=0.028 mM), HBeAg (IC(50)=0.027 mM) and remarkable selective indices (SI(HBsAg) >90, SI(HBeAg) >93).

LC-MS Guided Isolation of (+/-)-Sweriledugenin A, a Pair of Enantiomeric Lactones, from Swertia leducii

(±)-Sweriledugenin A, a pair of novel enantiomeric lactones, were isolated from Swertia leducii under the guidance of LC-MS investigation. The enantiomeric separation was achieved by HPLC on a chiral column. Their structures were determined by extensive NMR spectra, X-ray, and quantum calculations. (+)-Sweriledugenin A and (-)-sweriledugenin A showed activities inhibiting HBV DNA replication with the IC50 values of 36.86 and 26.55 μM on the HepG 2.2.15 cell line in vitro.

Swerilactones C and D, anti-HBV New Lactones from a Traditional Chinese Herb: Swertia mileensis

Swerilactones C (1) and D (2), two novel diastereomeric lactones with an unprecedented 6/6/6/6/6 pentacyclic ring system, were isolated from the traditional Chinese herb Swertia mileensis. Their structures and relative stereochemistry were elucidated on the basis of spectroscopic methods and further confirmed by X-ray single-crystal diffraction analysis. In vitro antihepatitis B virus (HBV) assay on the Hep G 2.2.15 cell line showed that both compounds 1 and 2 exhibited inhibitory activities against the secretion of HBsAg (IC(50) = 1.24 and 2.96 mM, respectively) and HBeAg (IC(50) = 0.77 and 1.47 mM, respectively).

Two new compounds from the roots of Ligusticum chuanxiong

Two new compounds, named ligusticoside A (1), a novel phthalide derivative with a lactone ring, and 4-pentylcyclohex-3-ene-1α,2β-diol (2), were isolated from the rhizomes of Ligusticum chuanxiong. Their structures were determined by spectral methods (MS, IR, UV, 1D and 2D NMR). An X-ray diffraction experiment was performed to confirm the structure of compound 1.

(±)-Paeoveitol, a Pair of New Norditerpene Enantiomers from Paeonia veitchii

(+)-Paeoveitol and (-)-paeoveitol, a pair of new norditerpene enantiomers, were isolated from the root of Paeonia veitchii. Their structures and absolute configurations were determined on the basis of extensive analysis of 1D and 2D NMR spectra, crystal X-ray diffraction, and electronic circular dichroism (ECD). A possible biogenesis involving two molecules of paeoniflorin was postulated.

Catalytic Asymmetric Total Synthesis of (+)- and (−)-Paeoveitol via a Hetero-Diels–Alder Reaction

The first catalytic asymmetric total synthesis of (+)- and (-)-paeoveitol has been accomplished in 42% overall yield via a biomimetic hetero-Diels-Alder reaction. The chiral phosphoric acid catalyzed hetero-Diels-Alder reaction showed excellent diastereo- and enantioselectivity (>99:1 dr and 90% ee); two rings and three stereocenters were constructed in a single step to produce (-)-paeoveitol on a scale of 452 mg. This strategy enabled us to selectively synthesize both paeoveitol enantiomers from the same substrates by simply changing the enantiomer of the catalyst.