Achillinin A,a Cytotoxic Guaianolide from the Flower of Yarrow,Achillea millefolium

Achillinin A (2β,3β-epoxy-1α,4β,10α-trihydroxyguai-11(13)-en-12,6α-olide, 1), a new guaianolide isolated from the flower of Achillea millefolium, exhibited potential antiproliferative activity to A549, RERF-LC-kj and QG-90 cells with 50% inhibitory concentration (IC₅₀) values of 5.8, 10 and 0.31 μM, respectively.     

Sesquiterpenoids from Curcuma wenyujin with anti-influenza viral activities

Five sesquiterpenoids, 1α,8α-epidioxy-4α-hydroxy- 5αH-guai-7(11),9-dien- 12,8-olide. (1), 8,9-seco-4β-hydroxy-1α,5βH-7(11)-guaen-8,10-olide (2), 8α-hydroxy-1α, 4β,7βH-guai-10(15)-en- 5β,8β-endoxide(3), 7β,8α-dihydroxy-1α,4αH-guai-10(15)-en-5β,8β-endoxide(4) and 7-hydroxy-5(10),6,8-cadinatriene-4-one(5), together with seven known analogs were isolated from the rhizomes of Curcuma wenyujin. Their structures and relative configurations were determined on the basis of spectroscopic methods including 2D NMR techniques, and the structures of 1 and 2 were confirmed by single-crystal X-ray diffraction experiment. Compounds 1–10 and 12 showed significant in vitro antiviral activity against the influenza virus A with IC₅₀ values ranged from 6.80 to 39.97 μM, and SI values ranged from 6.35 to 37.25.     

土壤真菌 Aspergillus fumigatus固体发酵产物的化学成分及抗氧化活性研究

为研究来源于哀牢山国家级自然保护区河谷的土壤真菌Aspergillus fumigatus固体发酵产物的化学成分及抗氧化活性研究,采用正相硅胶柱层析、反相硅胶柱层析和Sephadex LH-20分离纯化,借助核磁共振波谱等方法鉴定化合物结构,从中共得到13个化合物,分别鉴定为rubrofusarin B(1)、rubrofusarin A(2)、carbonarone A(3)、aspernigrin A(4)、flavasperone(5)、(22 E,24 R)-5α,8α-过氧麦角甾-6,22-二烯-3β-醇(6)、(22 E,24 R)-5α,8α-过氧麦角甾-6,9(11),22-三烯-3β-醇(7)、ourosperone A(8)、(22 E,24 R)-麦角甾-5,7,22-三烯-3β-醇(9)、stigmast-1,5-dien-3β-ol(10)、fonsecinones A(11)、asperpyrone C(12)、asperpyrones B(13)。其中,化合物1~5和7~13为从该菌种中首次分离。抗氧化活性结果显示,化合物8对DPPH(IC₅₀=3.453 mg/mL)、ABTS+(IC₅₀=0.155 mg/mL)、OH(IC₅₀=0.019 mg/mL)自由基都有一定的清除效果。     

Synthesis of stryphnoside A, a triterpene saponin isolated from the pericarps of Stryphnodendron fissuratum

Stryphnoside A, α-l-rhamnopyranosyl 3β-O-[α-l-arabinopyranosyl-(1→4)-β-d-xylopyranosyl-(1→2)-β-d-glucopyranosyl]-2α-hydroxyolean-12-en-28-oate, has been synthesized in 11 steps in 15% overall yield starting from the naturally abundant oleanolic acid. Condensation of a partially protected glucopyranosyl donor and 2α,3β-dihydroxyolean-12-en-28-oic acid derivative using inverse glycosylation procedure has significantly simplified the target saponin synthesis. Stryphnoside A exhibited weak cytotoxic activities against tumor cells HeLa, A549, and HepG2 with IC₅₀ at mM level.     

Sterols from a soft coral, Dendronephthya gigantea as farnesoid X-activated receptor antagonists

Three new steroids 3-oxocholest-1,22-dien-12β-ol (1), 3-oxocholest-1,4-dien-20β-ol (2), 3-oxocholest-1,4-dien-12β-ol (3), and three known steroids (20S)-20-Hydroxyergosta-1,4,24(28)-trien-3-one (4) [7a], 5α,8α-Epidioxycholesta-6,22-dien-3β-ol (5) [10] and 5-cholestene-3β,12β-diol (6) [11] were isolated from a soft coral Dendronephthya gigantea. Their chemical structures and relative stereochemistry were elucidated by the analysis of HRMS and 2-D NMR spectroscopic data. The steroids 1 and 2 showed notable inhibitory activity against farnesoid X-activated receptor (FXR) with IC(50)'s 14 and 15μM.     

Inhibition of sterol synthesis in L cells by 14alpha-ethyl-5alpha-cholest-7-en-15alpha-ol-3-one at nanomolar concentrations

14α-Ethyl-5α-cholest-7-en-15α-ol-3-one was prepared in 85% yield by selective oxidation of the 3β-hydroxyl function of 14α-ethyl-5α-cholest-7-en-3β,15α-diol by cholesterol oxidase. 14α-Ethyl-5α-cholest-7-en-15α-ol-3-one caused a 50% inhibition of the incorporation of [1-¹⁴C]-acetate into digitonin-precipitable sterols at a concentration of 6 × 10^?9M in L cells and a 50% reduction in level of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase activity in the same cells at a concentration of 4 × 10^?8 M.     

Synthesis and acetylcholinesterase inhibitory activity of 2β,3α-disulfoxy-5α-cholestan-6-one

Disodium 2β,3α-dihydroxy-5α-cholestan-6-one disulfate (8) has been synthesized using cholesterol (1) as starting material. Sulfation was performed using trimethylamine-sulfur trioxide complex in dimethylformamide as the sulfating agent. The acetylcholinesterase inhibitory activity of compound 8 was evaluated and compared to that of disodium 2β,3α-dihydroxy-5α-cholestane disulfate (10) and diols 7 and 9. Compounds 8 and 10 were active with IC(50) values of 14.59 and 59.65 μM, respectively. Diols 7 and 9 showed no inhibitory activity (IC(50)>500 μM).     

Chlorinated and diepoxy withanolides from Withania somnifera and their cytotoxic effects against human lung cancer cell line

Phytochemical studies on the aerial parts of Withania somnifera L. Dunal. (Solanaceae) led to the isolation of a chlorinated steroidal lactone (27-acetoxy-4β,6α-dihydroxy-5β-chloro-1-oxowitha-2,24-dienolide), a diepoxy withanolide (5β,6β,14α,15α-diepoxy-4β,27-dihydroxy-1-oxowitha-2,24-dienolide), and withaferin A. Their structures were elucidated by using spectroscopic techniques. All three compounds exhibited a growth inhibition and cytotoxic activity against human lung cancer cell line (NCI-H460), with withaferin A being the most potent (GI(50)=0.18 μg/mL and LC(50)=0.45 μg/mL) among three compounds tested.     

Two new cembranic diterpenoids from the flowers of Nicotiana tabacum L.

Two new cembranoids, together with fifteen known ones, were isolated from the flowers of Nicotiana tabacum L. The structures of the new compounds were established as (1βH,2E,4αOH,6αOH,7E,10αH,11αH,12βOH)-10,11-epoxy-2,7-cembradiene-4,6,12-triol (1) and (1βH,2E,4αOH,6αOH,7E,10βH,11βH,12αOH)-10,11-epoxy-2,7-cembradiene-4,6, 12-triol (2) by using spectroscopic analysis, including HRESIMS, IR, one- and two-dimensional NMR. A plausible biogenetic relationship of the isolated cembranoids was proposed. The antitumor activities of selected compounds against a panel of three human cancer HepG2, A549 and HCT-116 cell lines were evaluated by the MTT assay. Compound 5 exhibited moderate activity against Hep-G2 cell lines with an IC₅₀ value of 14.38 μM.     

朝鲜蓟叶中一个新的倍半萜内酯

从朝鲜蓟（Cynarascolyrnus）叶中分离得到2个倍半萜内酯,其中一个是新化合物,通过波谱学方法确定其结构为3β,8α,11α,13-四羟基-10（14）-愈创木烯-1α,4β,5α,6β氢-6α,12-内酯（1）。     

Azemiopsin from Azemiops feae viper venom, a novel polypeptide ligand of nicotinic acetylcholine receptor

Azemiopsin, a novel polypeptide, was isolated from the Azemiops feae viper venom by combination of gel filtration and reverse-phase HPLC. Its amino acid sequence (DNWWPKPPHQGPRPPRPRPKP) was determined by means of Edman degradation and mass spectrometry. It consists of 21 residues and, unlike similar venom isolates, does not contain cysteine residues. According to circular dichroism measurements, this peptide adopts a β-structure. Peptide synthesis was used to verify the determined sequence and to prepare peptide in sufficient amounts to study its biological activity. Azemiopsin efficiently competed with α-bungarotoxin for binding to Torpedo nicotinic acetylcholine receptor (nAChR) (IC(50) 0.18 ± 0.03 μm) and with lower efficiency to human α7 nAChR (IC(50) 22 ± 2 μm). It dose-dependently blocked acetylcholine-induced currents in Xenopus oocytes heterologously expressing human muscle-type nAChR and was more potent against the adult form (α1β1εδ) than the fetal form (α1β1γδ), EC(50) being 0.44 ± 0.1 μm and 1.56 ± 0.37 μm, respectively. The peptide had no effect on GABA(A) (α1β3γ2 or α2β3γ2) receptors at a concentration up to 100 μm or on 5-HT(3) receptors at a concentration up to 10 μm. Ala scanning showed that amino acid residues at positions 3-6, 8-11, and 13-14 are essential for binding to Torpedo nAChR. In biological activity azemiopsin resembles waglerin, a disulfide-containing peptide from the Tropidechis wagleri venom, shares with it a homologous C-terminal hexapeptide, but is the first natural toxin that blocks nAChRs and does not possess disulfide bridges.     

Two New Furanoeremophilanes from Senecio santelisis

From an Argentine collection of Senecio santelisis Phil ., the new furanoeremophilanoids, (10βH)‐6β‐acetoxy‐1α‐hydroxyfuranoeremophilan‐9‐one ( 1 ) and (10βH)‐1α‐hydroxy‐6β‐(propanoyloxy)furanoeremophilan‐9‐one ( 2 ), together with the known (10αH)‐6β‐acetoxy‐1α‐hydroxyfuranoeremophilan‐9‐one ( 3 ), (10αH)‐1α,6β‐diacetoxyfuranoeremophilan‐9‐one ( 4 ), and (10αH)‐1α‐hydroxy‐6β‐(propanoyloxy)furanoeremophilan‐9‐one ( 5 ) were isolated. Their structures and relative configurations were established on the basis of spectroscopic analysis. CHCl₃ Extract and pure compounds were evaluated for their antifungal activity. Compound 5 exhibited remarkable mycelial growth inhibition against B. cinerea with an IC₅₀ value of 21.4 μg/ml.     

9α,15-Dihydroxygermacra-1(10),4-dien-11β,13-dihydro-6α,12-olide,a germacranolide isolated from Centaurea aspera subsp. stenophylla

A new germacranolide, isolated from Centaurea aspera subsp. stenophylla, was identified as 9β,15-dihydroxygermacra-1 (10)4-dien-11β,l3-dihydro-6α,12-olide by spectroscopic evidence and partial synthesis.     

Antiserum to 5alpha-dihydrotestosterone: production, characterization and use in radioimmunoassay

5α-Dihydrotestosterone (5α-DHT) was rendered antigenic by covalent attachment to bovine serum albumin (BSA) through position 1 of the steroid. Nucleophilic attack by β-mercaptopropionic acid on the 1,2-dehydro derivative of 5α-DHT yielded the corresponding 1α-thioether alkanoic acid which was coupled to bovine serum albumin by use of the carbodiimide reagent. The method should be generally applicable to 3-oxosteroids. Immunization of rabbits with 5α-DHT-1α-carboxyethyl-thioether-BSA gave rise to antisera of high affinity for 5α-DHT (K_a= 1.4 × 10⁹ 1/mol) that showed little cross reaction with 17β-hydroxy-5β-androstan-3-one (3%), and with a variety of 17-oxoandrostane compounds (≤0.5%). However the serum cross-reacted significantly with testosterone (10%) and with 5α-androstene-3α, 17β-diol (16%). A radioimmunoassay procedure for the determination of 5α-DHT in plasma is described. Chromatographic purification of the plasma extracts proved necessary for obtaining valid results. The plasma level of 5α-DHT(pg/ml; ean ± S.D.) was 364±79 (n = 7) in normal human adult males and 188 ± 62 (n = 5) in normal non-pregnant women.     

Chemical characterization of milk oligosaccharides of the polar bear, Ursus maritimus

Two trisaccharides, three tetrasaccharides, two pentasaccharides, one hexasaccharide, one heptasaccharide, one octasaccharide and one decasaccharide were isolated from polar bear milk samples by chloroform/methanol extraction, gel filtration, ion exchange chromatography and preparative thin-layer chromatography. The oligosaccharides were characterized by ¹H-NMR as follows: the saccharides from one animal: Gal(α1-3)Gal(β1-4)Glc (α3′-galactosyllactose), Fuc(α1-2)Gal(β1-4)Glc (2′-fucosyllactose), Gal(α1-3)[Fuc(α1-2)]Gal(β1-4)Glc (B-tetrasaccharide), GalNAc(α1-3)[Fuc(α1-2)]Gal(β1-4)Glc (A-tetrasaccharide), Gal(α1-3)Gal(β1-4)GlcNAc(β1-3)Gal(β1-4)Glc, Gal(α1-3)[Fuc(α1-2)]Gal(β1-4)GlcNAc(β1-3)Gal(β1-4)Glc, Gal(α1-3)Gal(β1-4)GlcNAc(β1-3)[Gal(α1-3)Gal(β1-4)GlcNAc(β1-6)]Gal(β1-4)Glc; the saccharides from another animal: α3′-galactosyllactose, Gal(α1-3)Gal(β1-4)[Fuc(α1-3)]Glc, A-tetrasaccharide, GalNAc(α1-3)[Fuc(α1-2)]Gal(β1-4)[Fuc(α1-3)]Glc (A-pentasaccharide), Gal(α1-3)Gal(β1-4)[Fuc(α1-3)]GlcNAc(β1-3)Gal(β1-4)Glc, Gal(α1-3)Gal(β1-4)[Fuc(α1-3)]GlcNAc(β1-3)Gal(β1-4)[Fuc(α1-3)]Glc (difucosylheptasaccharide) and Gal(α1-3)Gal(β1-4)[Fuc(α1-3)]GlcNAc(β1-3){Gal(α1-3)Gal(β1-4)[Fuc(α1-3)]GlcNAc(β1-6)}Gal(β1-4)Glc (difucosyldecasaccharide). Lactose was present only in small amounts. Some of the milk oligosaccharides of the polar bear had α-Gal epitopes similar to some oligosaccharides in milk from the Ezo brown bear and the Japanese black bear. Some milk oligosaccharides had human blood group A antigens as well as B antigens; these were different from the oligosaccharides in Ezo brown and Japanese black bears.     

Novel taxa-4(20),12-diene and 2(3→20)abeotaxane from needles of Taxus canadensis

A novel 6/8/6-membered taxane with a rare C-12(13)-double bond and rare 2(3→20)abeotaxane were isolated from the needles of Taxus canadensis. Their structures were characterized as 7β,9α,10β-triacetoxytaxa-4(20),12-diene-2α,5α,11β-triol (1) and 2α,7β,10β-triacetoxy-5α-hydroxy-2(3→20)abeotaxa-4(20),11-diene-9,13-dione (2) on the basis of 1D and 2D spectroscopic data. 1 is the first example of a natural taxane without substitution at both C-13 and C-14.     

Pendulaosides A and B. Two acylated triterpenoid saponins from Harpullia pendula seed extract

Two new acylated triterpenoid saponins named pendulaosides A and B as well as the known phenolic compounds methyl gallate, gallic acid, 1,2,3,6-tera-O-galloyl-β-d-glucose and 1,2,3,4,6-penta-O-galloyl-β-d-glucose, were isolated from the seeds of Harpullia pendula. The structures of pendulaosides A and B were determined using extensive 1D and 2D NMR analysis and mass spectrometry as well as acid hydrolysis, as 3-O-β-d-glucopyranosyl-(1→2)-[α-L-arabinofuranosyl-(1→3)]-β-d-glucuronopyranosyl-22-O-angeloyl-3β,16α,22α,24β,28-pentahydroxylolean-12-ene and 3-O-β-d-glucopyranosyl-(1→2)-[α-L-arabinofuranosyl-(1→3)]-β-d-glucuronopyranosyl-16-O-(2-methylbutyroyl)-3β,16α,22α,24β,28-pentahydroxylolean-12-ene, respectively. To the best of our knowledge the two triterpene parts 22-O-angeloyl-3β,16α,22α,24β,28-pentahydroxylolean-12-ene and16-O-(2-methylbutyroyl)-3β,16α,22α,24β,28-pentahydroxylolean-12-ene have never been characterized before. The two isolated saponins were assayed for their in-vitro cytotoxic activity against the three human tumor cell lines HepG2, MCF7 and PC3. The results showed that pendulaoside A exhibited moderate activity on PC3 cell line with IC50value equal to 13.0 μM and weak activity on HepG2 cell line with IC50 value equal to 41.0 μM. Pendulaoside B proved to be inactive against the three used cell lines.     

Glechomanolides and eudesmanolides from Smyrnium perfoliatum

In addition to five known sesquiterpenoids, six new compounds were isolated from Smyrnium perfoliatum. The new compounds were 1β-acetoxy-eudesma-3,7(11),8-trien-8,12-olide, 1β-acetoxyeudesma-4(15),7(11),8-trien-8,12-olide, 1β-10α;4α,5β-diepoxy-8β-isobutoxy-glechomanolide, 1β, 10α;4α,5β-diepoxy-8α-isobutoxy-glechomanolide, 1β,4α-dihydroxy-2α,3α-epoxy-eudesma-7(11),8-dien-8,12-olide, 1β,4α-dihydroxy-2α,3α-epoxy-8β-methoxy-eudesma-7(11)-en-8α,12-olide.     

Humirianthenolides,new degraded diterpenoids from Humirianthera rupestris

The tuber of Humirianthera rupestris (Icacinaceae) contains the degraded diterpenoids 3β,20-epoxy-30α- hydroxy- 14-oxo-9β-podocarpan-19,6β-olide (humirianthenolide A), 3β,20-epoxy-3α,14α-dihydroxy-9β-podocarpan-19,6β- olide (humirianthenolide B), 3β,20; 16,14-diepoxy-3α-hydroxy-17-nor-15-oxo-9β-abiet-13-en-19,6β-olide (humirianthenolide C), 3β,20-epoxy-3α,14-dihydroxy-13-oxo-9β-podocarp-8(14)-en-19,6β-olide (humirianthenolide D), 3β,20-epoxy-3α-hidroxy-14-oxo-8α,9β-podocarpan-19,6β-olide (humirianthenolide E) and 3β,20-epoxy-3α,14β- dihydroxy-8α,9β-podocarpan-19,6β-olide (humirianthenolide F). ¹H NMR and ¹³C NMR spectroscopy were efrective for the determination of the humirianthenolide structures.