Gui-Jie Zhang

Lycojaponicumins A-C, three alkaloids with an unprecedented skeleton from Lycopodium japonicum.

Lycojaponicumins A-C (1-3), three trace alkaloids isolated from Lycopodium japonicum, represent a unique heterocyclic skeleton formed by the new linkage C4-C9. Notably, lycojaponicumins A and B (1 and 2) are the first examples of natural products possessing a 5/5/5/5/6 pentacyclic ring system with a 1-aza-7-oxabicyclo[2.2.1]heptane moiety. These structures were elucidated by spectroscopic methods and X-ray diffraction analysis. A plausible biogenetic pathway was proposed.

Bioactive Quassinoids from the Seeds of Brucea javanica

Six new quassinoids (1-6) and eight known compounds of this type (7-14) were isolated from the seeds of Brucea javanica. Their structures were elucidated by analysis of their spectroscopic data and from chemical evidence. Compounds 1-5 were found to be unusual quassinoids with a 2,3-seco A ring. The configurations at C-4 in 4 and 5 were determined by a difference circular dichroism method. In in vitro bioassays, 8 and 10 showed inhibitory activities for nitric oxide production in LPS-activated macrophages, with IC(50) values of 1.9 and 5.0 μM, respectively, while compounds 6, 8-11, 13, and 14 exhibited cytotoxicity against five human tumor cell lines (HCT-8, HepG2, BGC-823, A549, and SKVO3), having IC(50) values in the range 0.12-9.3 μM.

Diterpenoids and sesquiterpenoids from the roots of Illicium majus.

Five new diterpenoids (1-5), five new sesquiterpenoids (6-10), and three known compounds (11-13) were isolated from the roots of Illicium majus. Their structures were elucidated by extensive spectroscopic analysis. The absolute configuration of 1 was assigned by X-ray crystallography, whereas those of the 1,2-diol moieties in 3 and 4 were determined using Snatzkes method. The abietane acids 1, 2, 11, 12, and 13 displayed antiviral activity against the Coxsackie B3 virus, with IC50 values of 3.3-51.7 μM/mL.

Prenylated C6-C3 compounds from the roots of Illicium henryi.

Eleven prenylated C(6)-C(3) compounds, illihenryifunones A, B (1, 2), illihenryifunol A (3), illihenryipyranol A (4), illihenryiones A-G (5-11), and three known prenylated C(6)-C(3) compounds (12-14), were isolated from the roots of Illicium henryi. Structures of 1-11 were elucidated by spectroscopic methods including NMR, HRESIMS, and CD. The absolute configuration of the 11,12-diol moiety in 5 was determined by observing its induced circular dichroism after addition of Mo(2)(OAc)(4) in DMSO. The absolute configuration of C-11 in 4 was determined as S based on the Rh(2)(OCOCF(3))(4)-induced CD data; the absolute configuration of 3 was determined as R by comparison of its experimental and calculated electronic circular dichroism (ECD). The antioxidant activities of compounds 1-14 were also evaluated. Compound 4 exhibited strong antioxidant activity with an IC(50) value of 2.97±1.30 μM, whereas compounds 3 and 8 showed antioxidant activities with IC(50) values of 44.36±0.30 and 48.00±2.01 μM, respectively.

Diterpenoids and Sesquiterpenoids from the Twigs and Leaves of Illicium majus

Four new abietane diterpenes (1-4) and two new cycloparvifloralone-type sesquiterpenoids (5-6) have been isolated from the twigs and leaves of Illicium majus, together with three known sesquiterpenoids and five known diterpenoids. Their structures were determined by spectroscopic analysis and chemical methods. The absolute configuration of the 15,16-diol moiety in 2 is confirmed by Snatzkes method, observing the induced circular dichroism after the addition of dimolybdenum tetraacetate in DMSO. Compound 2 exihibited significant anti-inflammatory activity with an IC50 value of 0.26 ± 0.03 µM, while compounds 10, 11, and 13 showed good anti-inflammatory activities with IC50 values ranging from 1.94 ± 0.56 to 2.60 ± 0.48 µM.

The antiviral effect of jiadifenoic acids C against coxsackievirus B3.

Coxsackievirus B type 3 (CVB3) is one of the major causative pathogens associated with viral meningitis and myocarditis, which are widespread in the human population and especially prevalent in neonates and children. These infections can result in dilated cardiomyopathy (DCM) and other severe clinical complications. There are no vaccines or drugs approved for the prevention or therapy of CVB3-induced diseases. During screening for anti-CVB3 candidates in our previous studies, we found that jiadifenoic acids C exhibited strong antiviral activities against CVB3 as well as other strains of Coxsackie B viruses (CVBs). The present studies were carried out to evaluate the antiviral activities of jiadifenoic acids C. Results showed that jiadifenoic acids C could reduce CVB3 RNA and proteins synthesis in a dose-dependent manner. Jiadifenoic acids C also had a similar antiviral effect on the pleconaril-resistant variant of CVB3. We further examined the impact of jiadifenoic acids C on the synthesis of viral structural and non-structural proteins, finding that jiadifenoic acids C could reduce VP1 and 3D protein production. A time-course study with Vero cells showed that jiadifenoic acids C displayed significant antiviral activities at 0–6 h after CVB3 inoculation, indicating that jiadifenoic acids C functioned at an early step of CVB3 replication. However, jiadifenoic acids C had no prophylactic effect against CVB3. Taken together, we show that jiadifenoic acids C exhibit strong antiviral activities against all strains of CVB, including the pleconaril-resistant variant. Our study could provide a significant lead for anti-CVB3 drug development.

Sesquiterpenes from the roots of Illicium jiadifengpi.

Two new sesquiterpenes (1, 2) and two new sesquiterpene glycosides (3, 4) with a seco-prezizaane skeleton, three new allo-cedrane sesquiterpene glycosides (5-7), and a new acorane sesquiterpene (8) as well as 15 known analogues were isolated from the roots of Illicium jiadifengpi used for the treatment of rheumatoid arthritis. The structures of these compounds were elucidated by extensive spectroscopic analysis and chemical methods. The absolute configurations of compounds 5-7 were confirmed by CD experiments. The configuration of compound 8 was assigned by single-crystal X-ray crystallographic analysis and CD experiments. Compounds 4, 6, 7, 14, and 23 showed moderate antiviral activities against Coxsackie virus B3, and all compounds were inactive when evaluated for their cytotoxic activities against five human tumor cell lines and neuroprotection.

Novel sesquiterpenoid glycosides and sesquiterpenes from the roots of Illicium henryi.

Seven new sesquiterpenoid glycosides, consisting of one thapsan-type (1), two capnellane-type (2 and 3), four floridanolide sesquiterpene glycosides (4-7), and one new azulene-type sesquiterpene (8), along with six known sesquiterpenes (9-14) were isolated from the roots of Illicium henryi. The structures of 1-8 were elucidated by extensive spectroscopic analyses and chemical methods. The absolute configurations of 1, 2, and 8 were determined based on Rh2(OCOCF3)4-induced CD, Mo2(OAc)4-induced CD data, and calculated electronic circular dichroism (ECD), respectively. Compound 1 was found to exhibit weak neurotoxicant activity.