Chenggen Zhu

Alkaloids from the Root of Isatis indigotica

Seventeen new alkaloids (1-17) and 14 known analogues have been isolated from an aqueous extract of the root of Isatis indigotica. The structures and absolute configurations of these compounds were determined by extensive spectroscopic data analysis, including 2D NMR, single-crystal X-ray crystallography using anomalous scattering of Cu Kα radiation, and electronic circular dichroism spectra calculations based on the quantum-mechanical time-dependent density functional theory. Compounds 1, 2, and 3 are the first examples of natural products with unique linkages between a molecule of 2-(4-methoxy-1H-indol-3-yl)acetonitrile and 2-(1H-indol-3-yl)acetonitrile, 2-(4-methoxy-1H-indol-3-yl)acetonitrile, and 4-hydroxyphenylethane, respectively. Compounds (-)-4 and (+)-4 represent the first natural products with the pyrrolo[2,3-b]indolo[5,5a,6-b,a]quinazoline skeleton. Some structural assignments for the new alkaloids suggest that the assignments made for certain previously reported alkaloids require revision. Compounds 1-3 and arvelexin (18) show antiviral activity against the influenza virus A/Hanfang/359/95 (H3N2), with IC(50) values of 3.70-12.35 μM, and 17 inhibits Coxsackie virus B3 replication with an IC(50) of 6.87 μM.

A minor diterpenoid with a new 6/5/7/3 fused-ring skeleton from Euphorbia micractina.

A novel diterpenoid with an unprecedented 6/5/7/3 fused-ring skeleton, euphorbactin (1), was isolated from an ethanol extract of the roots of Euphorbia micractina. The structure was determined by extensive spectroscopic studies, especially by 2D NMR and CD data analysis. A proposed biosynthetic pathway and preliminary investigations of the biological activity of compound 1 are also discussed.

Enantiomers of an indole alkaloid containing unusual dihydrothiopyran and 1,2,4-thiadiazole rings from the root of Isatis indigotica.

A pair of enantiomers (1a and 1b) of an indole alkaloid containing dihydrothiopyran and 1,2,4-thiadiazole rings was isolated from an aqueous extract of the root of Isatis indigotica. The structures and absolute configurations of the enantiomers were determined by extensive spectroscopic analysis, especially 2D NMR, modified Moshers method, and electronic CD (ECD). The proposed biosynthetic pathway and preliminary investigations of the biological activity of compounds 1a and 1b against influenza virus A/Hanfang/359/95 (H3N2) and HSV-1 are also discussed.

Bioactive neolignans and lignans from the bark of Machilus robusta.

Sixteen new neolignans and lignans (1-16), together with 12 known analogues, have been isolated from an ethanol extract of the bark of Machilus robusta. Compounds 1 and 2 showed activity against HIV-1 replication in vitro, with IC(50) values of 2.52 and 2.01 μM, respectively. At 10 μM, 6, 8, and 9 reduced dl-galactosamine-induced hepatocyte (WB-F344 cells) damage, and 9 could additionally attenuate rotenone-induced PC12 cell damage. The known compounds (-)-pinoresinol (17) and (+)-lyoniresinol (18) were active against serum deprivation induced PC12 cell damage.

Homo- and Heptanor-sterols and Tremulane Sesquiterpenes from Cultures of Phellinus igniarius

Four steroids, a homopregnene (1) and three heptanorergosterane derivatives (2-4), nine tremulane sesquiterpenes (5-13), and 18 known compounds have been isolated from cultures of the fungus Phellinus igniarius. Their structures and absolute configurations were elucidated by spectroscopic data analysis. In preliminary in vitro assays, at 10(-5) M, compounds 8, 9, 13, and 3beta-hydroxy-11,12-O-isopropyldrimene (14) showed significant vascular-relaxing activities against phenylephrine-induced vasoconstriction with relaxing rates of 35.7%, 45.4%, 46.6%, and 32.1%, respectively, as compared with the blank control.

Highly acylated diterpenoids with a new 3,4-secograyanane skeleton from the flower buds of Rhododendron molle.

Four highly acylated diterpenoids with a new 3,4-secograyanane skeleton, secorhodomollolides A-D (1-4), have been isolated from the flower buds of Rhododendron molle. Their structures including absolute configurations were determined on the basis of spectroscopic data interpretation and single-crystal X-ray crystallography. Compound 4 exhibited significant analgesic and sedative effects at a dose of 5 mg/kg, and compound 2 showed selective cytotoxic activity against human hepatoma carcinoma cell line (Bel-7402) with IC(50) 0.97 microM.

Diterpenoid alkaloids from the lateral root of Aconitum carmichaelii.

Twenty-six new diterpenoid alkaloids, 1-26 (1-4: hetisan-type C(20)-diterpenoid alkaloids; 5-26: aconitane C(19)-diterpenoid alkaloids), and two known analogues, hypaconitine 27 and benzoylmesaconine 28, have been isolated from a water extract of the lateral root of Aconitum carmichaelii. Compounds 7 and 8 are rare examples of conformational isomers obtained from the same material. The conformation and conformational transformation of ring A in the C(19)-diterpenoid alkaloids are discussed on the basis of NMR data analysis in combination with single-crystal X-ray crystallography of 6 and 27 by anomalous scattering of Cu Kα radiation. In preliminary analgesic and toxicity assays, the isomer with ring A in the chair conformation (8 or 27) was found to be more active than that with ring A in the boat conformation (7 or 27a). In addition, 15, 16, and 19 showed neuroprotective activity.

Aromatic glycosides from the flower buds of Lonicera japonica

Six new glycosides (1–6) have been isolated from the flower buds of Lonicera japonica. Their structures including the absolute configurations were determined by spectroscopic and chemical methods as ( − )-2-hydroxy-5-methoxybenzoic acid 2-O-β-d-(6-O-benzoyl)-glucopyranoside (1), ( − )-4-hydroxy-3,5-dimethoxybenzoic acid 4-O-β-d-(6-O-benzoyl)-glucopyranoside (2), ( − )-(E)-3,5-dimethoxyphenylpropenoic acid 4-O-β-d-(6-O-benzoyl)-glucopyranoside (3), ( − )-(7S,8R)-(4-hydroxyphenylglycerol 9-O-β-d-[6-O-(E)-4-hydroxy-3,5-dimethoxyphenylpropenoyl]-glucopyranoside (4), ( − )-(7S,8R)-(4-hydroxy-3-methoxyphenylglycerol 9-O-β-d-[6-O-(E)-4-hydroxy-3,5-dimethoxyphenylpropenoyl]-glucopyranoside (5), and ( − )-4-hydroxy-3-methoxyphenol β-d-{6-O-[4-O-(7S,8R)-(4-hydroxy-3-methoxyphenylglycerol-8-yl)-3-methoxybenzoyl]}-glucopyranoside (6), respectively.

Chemical constituents of Heteroplexis micocephala.

Eleven new compounds including two sesquiterpenes with an unusual 2,2,5,9-tetramethylbicyclo[6.3.0]undecane carbon skeleton (1 and 2), five phytane-type diterpene dilactones (3-7), an ent-clerodane diterpene dilactone (8), and three phenylpropenol esters (9-11), together with a diacylphenol (12) and 38 known compounds, have been isolated from an ethanolic extract of Heteroplexis micocephala. Their structures including absolute configurations were elucidated by spectroscopic and chemical analyses. In the in vitro assays, compound 6 showed a selective cytotoxic activity against A2780 with an IC(50) value of 4.37 microM, while sinapyl diangelate (13) showed a potent activity inhibiting HIV-1 replication with an IC(50) value of 4.04 microM.

C14-Polyacetylene glucosides from Codonopsis pilosula

Seven new C14-polyacetylene glucosides codonopilodiynosides A–G (1–7) were isolated from an aqueous extract of the Codonopsis pilosula roots. Their structures were determined by spectroscopic and chemical methods as (–)-(5S,6E,12E)-tetradeca-6,12-dien-8,10-diyn-1,5,14-triol 5-O-β-d-glucopyranoside (1), (–)-(5S,6E,12E)-tetradeca-6,12-dien-8,10-diyn-1,5,14-triol 5-O-β-d-glucopyranosyl-(1″ → 2′)-β-d-glucopyranoside (2), (–)-(5S,6E,12E)-tetradeca-6,12-dien-8,10-diyn-1,5,14-triol 5,14-di-O-β-d-glucopyranoside (3), (–)-(5S,6E)-tetradeca-6-en-8,10-diyn-1,5,14-triol 5-O-β-d-glucopyranoside (4), (–)-(5S,6E,12E)-tetradeca-6,12-dien-8,10-diyn-1,5-diol 5-O-β-d-glucopyranosyl-(1″ → 2′)-β-d-glucopyranoside (5), (–)-(6S,4E,12E)-tetradeca-4,12-dien-8,10-diyn-1,6-diol 6-O-β-d-glucopyranosyl-(1″ → 2′)-β-d-glucopyranoside (6), and (–)-(5S,6E)-tetradeca-6-en-1,5-epoxy-8,10-diyn-14-ol 14-O-β-d-glucopyranosyl-(1″ → 2′)-β-d-glucopyranoside (7), respectively. The absolute configurations of 1–7 were assigned by enzymatic hydrolysis followed by isolation of glucose and aglycones (1a and 4a–7a), and subsequent comparison of specific rotation, TLC, and 1H NMR data of the glucose with an authentic sugar sample and application of modified Moshers method based on the MPA determination rule of ΔδRS values for 1a and 4a, and ΔδS values for 6a. The configuration of 7 was assigned by electronic circular dichroism calculations based on the quantum-mechanical time-dependent density functional theory.