Total synthesis of natural product (R)-4-phenyl-2-O-[beta-D-xylopyranosyl(1-->6)-beta-D-glucopyranosyl]butane and its epimer.

The new compound (R)-4-phenyl-2-O-[beta-d-xylopyranosyl(1 --> 6)-beta-D-glucopyranosyl]butane (1) and its epimer (2), together with (R)-4-phenyl-2-O-beta-D-glucopyranosyl butane (24) and (S)-4-phenyl-2-O-beta-D-glucopyranosyl butane (25) were firstly synthesized from 4-phenylbutan-2-one and glucose. The absolute configuration of C-2 for 1 was confirmed as R. Their anti-tumour activities were evaluated.

Synthesis of three natural diosgenyl glycosides.

Three well-known natural diosgenyl glycosides which have the same sugar chains but different sequence, ophipogonin C', polyphillin C and prosapogenin B, were synthesised by a facile approach. A method using the levulinyl group as a protecting group to selectively mask the C3-OH of diosgenyl 4,6-O-benzylidene-beta-D-glucopyranoside is described.

Total synthesis and biological evaluation of (+)- and (-)-Butyl ester of rosmarinic acid.

An efficient method for the synthesis of the natural product (+)-(R)-butyl ester of rosmarinic acid (+)-(R)-1 and its enantiomer ( - )-(S)-1 has been developed by chemical resolution of its phenyl lactic acid precursors 4 with ( - )-menthol. Their antioxidative and anti-tumor activities were evaluated.

Purification and characterization of a new peptide with analgesic effect from the scorpion Buthus martensi Karch.

Anew peptide, designated as Buthus martensi Karch (BmK) AngM1, with an isoelectric point (pI) of 5.8 was purified and characterized from the venom of Buthus martensi Karch. The molecular mass was calculated as 7040.5 Da from multiple-charged ions by elelctrospray ionization mass spectroscopy (ESI/MS). The complete amino acid sequence of BmK AngM1 of 64 amino acid residues was determined by automatic sequencing of N-terminal part of the native peptide and the fragments of reduced and S-carboxymethylated (RCM)-peptide degraded by Staphylococcus aureaus V(8) protease and TPCK(N-p-Tosyl-L-phenylalanine chloromethyl ketone)-treated trypsin. Bioactivity tested using mouse-twisting model showed an evident analgesic effect with 63.0% (P < 0.001) inhibition efficiency at the dose of 0.8 mg/kg, but the LD(50) was larger than 50 mg/kg. Electrophysiological studies showed that BmK AngM1 at the concentration of 1 microm obviously inhibit voltage-dependent Na(+) current (I(Na)) and voltage-dependent delayed rectifier K(+) current (I(K)) but had no effects on transient K(+) current.

Purification, characterization of two peptides from Buthus martensi Karch.

A new peptide named Martentoxin I and an analogue Martentoxin were purified and characterized from the venom of Buthus martensi Karch. Martentoxin I consisted of 36 amino acid residues with molecular mass as 3908.0 Da determined by matrix-assisted laser desorption ionization time-of-flight-MS. The amino acid sequence was determined as GLIDVKCFASSECWTACKKVTGSGQGKCQNNQCRCY by Edman degradation. Martentoxin consisted of 37 amino acid residues with a molecular mass as 4055.3 Da and it showed highly sequence identity to Martentoxin I as FGLIDVKCFASSECWTACKKVTGSGQGKCQNNQCRCY. Estimation from circular dichroism spectra indicated Martentoxin I owned 18.0% alpha-helix, 53.0% beta-sheet structure and 3.9% turn while Martentoxin contained 13.3% alpha-helix, 64.3% beta-sheet structure and 1.1% turn. The toxicity assay showed both peptides had no toxic effects on mice up to the dose of 10 mg/kg. Electrophysiological studies showed that Martentoxin I and Martentoxin at the concentration of 1 microm significantly inhibited voltage-dependent Na+ current (INa) and voltage-dependent delayed rectifier K+ current (IK) but had no effects on transient K+ current (IA). Both interactions with Na+ and K+ channels were irreversible.

Five new diprenylated flavonols from the leaves of Broussonetia kazinoki.

Five new diprenylated flavonols, broussonol A (1), broussonol B (2), broussonol C (3), broussonol D (4), and broussonol E (5), along with two known compounds, were isolated from an ethanolic extract of the leaves of Broussonetia kazinoki. Their structures were elucidated by chemical and spectral methods. Cytotoxic activities were evaluated against several different cell lines.

New annonaceous acetogenins from the roots of Uvaria calamistrata.

Five new annonaceous acetogenins, calamistrins C-G (1-5), were isolated from an ethanolic extract of the roots of Uvaria calamistrata. Compounds 1-3 were mono-THF ring acetogenins; compounds 4 and 5 were bis-THF acetogenins, with the THF rings from C-18 to C-25. The absolute configurations of 3, 4, and 5 as well as the partial absolute configurations of 1 and 2 were determined by (13)C NMR spectroscopy and advanced Mosher methodology.

Calamistrins A and B, two new cytotoxic monotetrahydrofuran annonaceous acetogenins from Uvaria calamistrata.

Two new bioactive monotetrahydrofuran acetogenins, calamistrins A (1) and B (2), and two known compounds, uvarigrin (3) and uvarigranin (4), have been isolated from the roots of Uvaria calamistrata. The structures of the new compounds were elucidated by spectroscopic and chemical methods. The absolute stereochemistry of the stereogenic centers was established by Mosher ester methodology.

Styryllactones from the rhizomes of Goniothalamus griffithii.

Three new styryl-lactones 8-acetylgoniofufurone(1), 7-acetylgonio-pypyrone(3), and 5-acetylgoniopypyrone(4), along with ten known compounds, goniofufurone(2), goniopypyrone(5), goniothalamin, goniothalenol, (+)-isoaltholactone, goniodiol, 7-acetylgoniodiol, goniotriol, 8-acetylgoniotriol, 9-deoxygoniopypyrone were isolated from the rhizomes of Goniothalamus griffithii Hook f. et. Thoms. Their structures were elucidated by IR, MS, NMR spectra and chemical evidence. All compounds showed cytotoxic activities against human cancer cell lines.

Two linear acetogenins from Goniothalamus gardneri.

Two new acetogenins, gardnerilins A and B, have been isolated from the roots of Goniothalamus gardneri. Both are C35 acetogenins containing non-tetrahydrofuran rings. Their structures have been established on the basis of spectral evidence.

Linear acetogenins from Goniothalamus donnaiensis.

Four linear acetogenins, donhepocin (1), 34-epi-donhepocin (1'), donhexocin and donbutocin, have been isolated from the roots of Goniothalamus donnaiensis. 1 and 1', isolated as an epimeric pair, contain a rare gamma-hydroxymethyl-gamma-lactone. Their structures have been established on the basis of spectral and chemical evidence.

Two epimeric pairs of C-4-acetyl annonaceous acetogenins from Goniothalamus donnaiensis.

Further studies on the roots of Goniothalamus donnaiensis Finet et Gagnap (Annonaceae) led to the isolation of two pairs of Annonaceous acetogenins, donnaienin C ( 1) and 34- EPI-donnaienin C ( 1'), donnaienin D ( 2) and 34- EPI-donnaienin D ( 2'), containing a rare gamma-hydroxymethyl-gamma-lactone moiety and a C-4-acetoxy group. Their structures were elucidated by spectral data and chemical derivatization. Preliminary pharmacological tests showed that the mixture of donnaienin C( 1) and 34- EPI-donnaienin C ( 1') inhibited human hepatoma (Bel) cell lines in vitro (IC (50), 7.1 microg/ml).

[Studies on new cytotoxic annonaceous acetogenins from Uvaria grandiflora and absolute configurations].

Two new cytotoxic annonaceous acetogenins, named uvarigrin(1) and uvarigrandin A(3), were obtained from the roots of Uvaria grandiflora Roxb(Annonaceae). Based on X-ray analysis and Mosher's methodology, the overall absolute configuration of 1 was established as 15S, 17R, 18R, 21R, 22R, 36S. The absolute configuration of 3 was also resolved by Mosher's methodology. The relative configuration of the previously reported uvarigranin (2) was revised. Compound 1 showed cytotoxicity against HCT-8, Bel7402 and A2780 human tumor cell lines at ED50 levels of 0.15, 0.21 and 0.41 microgram.ml-1, respectively.

[Studies on synthesis and pharmacological activities of cimicifugamide from Cimicifuga dahurica, and its analogues].

The total synthesis of cimicifugamide, a new natural compound isolated from the roots of Cimicifuga dahurica, was accomplished by a reaction sequence of seven steps in an overall yield of 31%. Trifluoroacetoxy was used as leaving group at the anomeric carbon. The target product was characterized by IR, MS, 1HNMR, 13CNMR and elemental analysis. In addition, seven analogues were synthesized and their preliminary pharmacological activities were tested.

Tonkinelin: a novel annonaceous acetogenin from Uvaria tonkinensis.

Further studies on the root bark of Uvaria tonkinensis Finet et Gagnep. (Annonacease) led to the isolation of a new Annonaceous acetogenin, tonkinelin (1). The structure of 1 was elucidated on the basis of spectral data and chemical evidence. This compound represents an unusual type of C37 Annonaceous acetogenin, having neither tetrahydrofuran (THF) nor epoxide rings and possessing only a vicinal diol in the hydrocarbon chain. Preliminary pharmacological tests showed that tonkinelin (1) inhibits human leukemia (HL-60) and human colon adenocarcinoma (HCT-8) cell lines in vitro.

Tonkinecin, a novel bioactive annonaceous acetogenin from Uvaria tonkinesis.

A novel bioactive monotetrahydrofuran acetogenin named tonkinecin (1) and two known compounds, uvariamicins I and II, have been isolated from the roots of Uvaria tonkinesis. The structure of 1 was elucidated using spectral methods and its absolute stereochemistry established by 1H-NMR experiments utilizing Mosher ester methodology.

[Studies on diterpenoids from leaves of Tripterygium wilfordii].

Tripterygium wilfordii Hook f. has been used as a medicinal herb in traditional Chinese medicine and as an insecticide by the Chinese for hundreds of years. Recently, this plant has been used to treat cancer, rheumatic arthritis and various skin diseases in some Chinese clinics. It is of interest to note that Tripterygium also showed significant antifertility activities. The active principles of the anti-inflammatory, immunosuppressive and antifertile actions in Tripterygium are diterpenoid containing triepoxides, but information on its chemistry is limited to the woody part of the root and the root bark. Recently, we have studies the leaves of Tripterygium (collected at Zhejiang province, China), and isolated two novel diterpenoids by chromatography named tripdioltonide (8) and 13,14-epoxide 9,11,12-trihydroxytriptolide (9), besides triptonide (1), triptolide (2), tripdiolide (3), triptolidenol (4), 16-hydroxyl-triptolide (5), tripchlorolide (6) and triptriolide (7). Their structures were established by chemical reactions, TLC, UV, MS, IR, 1H-1H COSY, 1H-13C COSY, DEPT spectrometric investigation. The structure of tripdioltonide was further confirmed by X-ray analysis.

[Application of 2d NMR techniques in the structure determination of ganosporelactone A and B].

Structure and stereochemistry of ganosporelactone A and B isolated from the spores of Ganoderma lucidum have been elucidated by the use of 1H-1H COSY, 1H-13C COSY, 1H-13C COLOC and NOESY 2D NMR spectroscopy. Ganosporelactone A and B are two novel pentacyclic triterpenoids which may be biogenetically derived from lanostane skeleton through the construction of C16 and C23 bond.