Bacopaside III,bacopasaponin G,and bacopasides A,B, and C from Bacopa monniera

Two new saponins, 3-O-[6-O-sulfonyl-beta-d-glucopyranosyl-(1-->3)]-alpha-l-arabinopyranosyl pseudojujubogenin (1) and 3-O-[alpha-l-arabinofuranosyl-(1-->2)]-alpha-l-arabinopyranosyl jujubogenin (2), a new matsutaka alcohol derivative, (3R)-1-octan-3-yl-(6-O-sulfonyl)-beta-d-glucopyranoside (3), a new phenylethanoid glycoside, 3,4-dihydroxyphenylethyl alcohol (2-O-feruloyl)-beta-d-glucopyranoside (4), and a new glycoside, phenylethyl alcohol [5-O-p-hydroxybenzoyl-beta-d-apiofuranosyl-(1-->2)]-beta-d-glucopyranoside (5), were isolated from Bacopa monniera. Their structures were established by NMR, MS, and chemical methods.     

Microbial O-demethylation, hydroxylation, sulfation, and ribosylation of a xanthone derivative from Halenia elliptica

1-Hydroxy-2,3,5-trimethoxyxanthone (1), one of the major xanthone derivatives isolated from Halenia elliptica, was biotransformed by two fungi, Trichothecium roseum and Paecilomyces marquandii. Transformation of 1 by T. roseumgave 1,5-dihydroxy-2,3-dimethoxyxanthone (2), 5-O-sulfate-1-hydroxy-2,3-dimethoxyxanthone (3), 5-O-sulfate-1-hydroxy-2,3,7-trimethoxyxanthone (4), 5-O-beta-ribofuranosyl-1-hydroxy-2,3-dimethoxyxanthone (5), and 1,5,6-trihydroxy-2,3-dimethoxyxanthone (6). Compound 2 was also formed by P. marquandii. The structures of the isolated compounds were elucidated by spectroscopic analyses. Among the five microbial-converted compounds, 3, 4, 5, and 6 are new compounds.     

Isolation and structure of homotemsirolimuses A, B, and C

Homotemsirolimuses A, B, and C (2a, 2b, 2c) were found to be minor components of a temsirolimus preparation made from rapamycin. These three temsirolimus analogues are derived from the corresponding rapamycin analogues, homorapamycins A, B, and C (1a, 1b, 1c) produced by the strain Streptomyces hygroscopicus. The structures of homotemsirolimuses A, B, and C were determined by spectroscopic methods. These compounds were tested for mTOR kinase inhibition and in two proliferation assays using LNCap prostate and MDA468 breast cancer cells. The results suggested that the mTOR inhibition and antiproliferation potencies for 2a, 2b, and 2c are comparable to those of rapamycin (1) and temsirolimus (2).     

Oumarone, bissaone, and aissatone, unusual prenylated polyketides from harrisonia abyssinica

Fractionation of the n-hexane extract of the leaves of Harrisonia abyssinica, collected in Guinea, afforded three novel and unusual prenylated polyketides, which were named oumarone (1), bissaone (2), and aissatone (3). Their structures were elucidated by spectroscopic methods, mainly 1D and 2D NMR spectroscopy.     

Stereochemical analysis of leubethanol, an anti-TB-active serrulatane, from Leucophyllum frutescens

Bioactivity-guided fractionation of the methanolic root bark extract of Leucophyllum frutescens led to the identification of leubethanol (1), a new serrulatane-type diterpene with activity against both multi-drug-resistant and drug-sensitive strains of virulent Mycobacterium tuberculosis. Leubethanol (1) was identified by 1D/2D NMR data, as a serrulatane closely related to erogorgiane (2), and exhibited anti-TB activity with minimum inhibitory concentrations in the range 6.25-12.50 μg/mL. Stereochemical evidence for 1 was gleaned from 1D and 2D NOE experiments, from 1H NMR full spin analysis, and by comparison of the experimental vibrational circular dichroism (VCD) spectrum to density functional theory calculated VCD spectra of two diastereomers.     

Taxezopidines M and N, taxoids from the Japanese yew, Taxus cuspidata

Two new taxoids, taxezopidines M (1) and N (2), have been isolated from seeds of the Japanese yew, Taxus cuspidata, and new structures were elucidated on the basis of spectroscopic data. The absolute configuration of a 3-N,N-(dimethylamino)-3-phenylpropanoyl group in 1 and 2 was determined to be R in each case by chiral HPLC analysis. The effect of 1 and 2 on the CaCl(2)-induced depolymerization of microtubules was investigated.     

N-hydroxypyridones, phenylhydrazones, and a quinazolinone from Isaria farinosa

New N-hydroxypyridones, militarinones E (1) and F (2), phenylhydrazones, farylhydrazones A (3) and B (4), a quinazolinone, 2-(4-hydroxybenzyl)quinazolin-4(3H)-one (5), and the known militarinones A (6) and B (7) were isolated from cultures of the Cordyceps-colonizing fungus Isaria farinosa. The structures of 1-5 were elucidated by spectroscopic methods, and 3 was confirmed by X-ray crystallography. The absolute configuration of the C-4' secondary alcohol in 1 was deduced via the circular dichroism data of the in situ formed [Rh(2)(OCOCF(3))(4)] complex. Compounds 1 and 6 showed significant cytotoxicity against A549 cells, whereas 7 was active against Staphylococcus aureus, Streptococcus pneumoniae, and Candida albicans.     

Myxostiolide, myxostiol, and clavatoic acid, plant growth regulators from the fungus Myxotrichum stipitatum

New plant growth regulators, named myxostiolide (1), myxostiol (2), and clavatoic acid (3), have been isolated from Myxotrichum stipitatum, and their structures have been established by spectroscopic methods including 2D NMR. The biological activities of 1, 2, and 3 have been examined using tea pollen and lettuce seedling bioassay methods. With tea pollen, compound 1 inhibited the pollen tube growth to 14% of control at a concentration of 100 mg/L. With lettuce seedlings, compound 2 accelerated the root growth from 1 mg/L to 100 mg/L and compound 3 inhibited the root growth, to 52% of control, at a concentration of 100 mg/L.     

Vittatalactone, a beta-lactone from the striped cucumber beetle, Acalymma vittatum

A novel beta-lactone, vittatalactone (1), was isolated from collections of airborne volatile compounds from feeding male striped cucumber beetles, Acalymma vittatum. The structure of 1 was determined to be (3R,4R)-3-methyl-4-(1,3,5,7-tetramethyloctyl)oxetan-2-one by microderivatization, GC-MS, and NMR studies. The absolute configurations at C-2 and C-3 on the beta-lactone ring were assigned by use of the modified Mosher method, applied to the beta-hydroxy acid methyl ester resulting from methanolysis of 1. Biological activity of 1, possibly as an aggregation pheromone for A. vittatum, was indicated by electrophysiological studies using beetle antennae and by the production of 1 by feeding male, and not female, beetles.     

Dictyoquinazols A,B, and C,new neuroprotective compounds from the mushroom Dictyophora indusiata

In an effort to identify neuroprotective compounds against excitatory neurotoxins from edible and medicinal mushrooms, dictyoquinazols A (1), B (2), and C (3) have been isolated from the methanolic extract of the mushroom Dictyophora indusiata. On the basis of NMR studies, their structures have been assigned as unique quinazoline compounds, which are very rare in nature. 2 and 3 existed as mixtures of rotamers (2a, 2b and 3a, 3b) inseparable by HPLC because of fast interconversion. The E/Z isomers of these compounds were assigned by comparison of (1)H NMR, (13)C NMR, and NOESY spectra and by (3)J(C,H) coupling constants. Dictyoquinazols protected primary cultured mouse cortical neurons from glutamate- and NMDA-induced excitotoxicities in a dose-dependent manner.     

The complestatins as HIV-1 integrase inhibitors. Efficient isolation, structure elucidation, and inhibitory activities of isocomplestatin, chloropeptin I, new complestatins, A and B, and acid-hydrolysis products of chloropeptin I

From the screening of a microbial extract library, isocomplestatin (1), a new axial-chiral isomer of complestatin (2) which is a known rigid bicyclic hexapeptide, was identified as a potent natural product inhibitor of HIV-1 integrase, a unique enzyme responsible for viral replication. Isocomplestatin showed inhibitory activities (IC(50)) in coupled 3'-end processing/strand transfer (200 nM), strand transfer (4 microM), and HIV-1 replication (200 nM) in virus-infected cells. Attempted large-scale isolation of 1 by the literature method, used for the isolation of complestatin, led to lower yield and limited availability. We have developed several new, two-step, high-yielding absorption/elution methods of isolation based on reverse-phase chromatography at pH 8 that are applicable to scales from one gram to potential industrial quantities. We have also discovered and determined the structure of two new congeners of 1, namely, complestatins A (4) and B (5), with almost equal HIV-1 integrase activity. They differ from 1 at C2' and C3' of the tryptophan moiety (residue F). Selective acid hydrolysis of chloropeptin I (3), itself a known acid-catalyzed rearranged isomer of 1 and 2 (8'- vs 7'-substitution in tryptophan residue F, respectively), an isomer of complestatin, and isocomplestatin resulted in a number of fragments (6-10) with retention of most of the HIV-1 integrase activity. The structure-activity relationship as revealed by these compounds could possibly lead to the design of better inhibitors or understanding of the HIV-1 integrase target.     

An efficient conversion of (3R,3'R,6'R)-lutein to (3R,3'S,6'R)-lutein (3'-epilutein) and (3R,3'R)-zeaxanthin

Two dietary carotenoids, (3R,3'R,6'R)-lutein (1) and (3R,3'R)-zeaxanthin (2), and their metabolite (3R,3'S,6'R)-lutein (3'-epilutein) (3) accumulate in human serum, milk, and ocular tissues. There is increasing evidence that compounds 1 and 2 play an important role in the prevention of age-related macular degeneration. Therefore, the availability of these carotenoids for metabolic studies and clinical trials is essential. Compound 1 is isolated from extracts of marigold flowers (Tagete erecta) and is commercially available, whereas 2 is only accessible by a lengthy total synthesis, and a viable method for synthesis of 3 has not yet been developed. This report describes an efficient conversion of technical grade 1 to 2 via 3. Acid-catalyzed epimerization of 1 yields an equimolar mixture of diastereomers 1 and 3. The mixture was separated by enzyme-mediated acylation with lipase AK from Pseudomonas fluorescens that preferentially esterified 3 and after alkaline hydrolysis yielded this carotenoid in 90% diastereomeric excess (de). Compound 3 was also separated from 1 in 56-88% de by solvent extraction and low-temperature crystallization, Soxhlet extraction, or supercritical fluid extraction. Base-catalyzed isomerization of 3 gave 2 in excellent yield, providing a convenient alternative to the total synthesis of this important dietary carotenoid.     

New decalin derivatives, eujavanoic acids A and B, from Eupenicillium javanicum

Two new decalin derivatives, eujavanoic acids A (1) and B (2), were isolated from Eupenicillium javanicum, along with several compactin derivatives. The structures of 1 and 2 were determined by spectroscopic methods and modified Mosher's method. The side chain (2-methylbutanoyloxy) and acid functionalities of compactin derivatives were necessary to show the antifungal activity.     

复方七芍降压片对SHR大鼠P2Y6、MEK1/2、ERK1/2及血管重塑标志物MMP-9、TIMP-1蛋白表达的影响

目的研究复方七芍降压片对自发性高血压大鼠(SHR)肠系膜动脉中G蛋白偶联受体P2Y6、酪氨酸激酶受体(MEK1/2)、丝裂原活化蛋白激酶(ERK1/2)及血管重塑标志物基质金属蛋白酶-9(MMP-9)、组织基质金属蛋白酶抑制剂-1(TIMP-1)等蛋白表达的影响,探讨复方七芍降压片干预血管重塑的作用机制。方法将雄性SHR大鼠随机分为模型组、厄贝沙坦片组(13.5 mg·kg^-1)、复方七芍降压片组(8.73 g·kg^-1),每组10只,另设10只WKY大鼠为正常对照组;灌胃给药,每日1次,连续给药6周。采用无创血压仪测定每周大鼠尾动脉血压;ELISA法检测大鼠血清中白细胞介素-1β(IL-1β)水平;免疫组化法检测肠系膜动脉中P2Y6、MEK1/2、ERK1/2、MMP-9及TIMP-1蛋白的表达;肠系膜动脉组织HE染色后进行体视学分析,测量肠系膜动脉血管中膜厚度及相同位置的管腔直径,计算两者比值作为动脉壁厚度(WT)值。结果与正常对照组比较,模型组大鼠各周血压明显上升(P<0.01);肠系膜动脉P2Y6、MEK1/2、ERK1/2、MMP-9蛋白表达及MMP-9/TIMP-1比值、WT值明显升高(P<0.05,P<0.01),TIMP-1表达明显降低(P<0.01);血清中IL-1β水平明显升高(P<0.01)。药物干预后,与模型组比较,复方七芍降压片组各周血压均明显降低(P<0.01);肠系膜动脉P2Y6、MEK1/2、ERK1/2、MMP-9蛋白表达及MMP-9/TIMP-1比值、WT值均明显降低(P<0.05,P<0.01),TIMP-1表达明显升高(P<0.05);血清中IL-1β水平明显降低(P<0.05)。结论复方七芍降压片能够显著降低SHR大鼠血压,改善血管重塑,可能与调控肠系膜动脉中P2Y6、MEK1/2、ERK1/2蛋白表达,减轻炎症反应有关。     

Flavonoid, iridoid, and lignan glycosides from Putoria calabrica

From the aerial parts of Putoria calabrica, two new flavonol triglycosides were isolated and their structures were elucidated as quercetin-3-O-[alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside]-7-O-beta-D-glucopyranoside (1, calabricoside A) and quercetin-3-O-[4' "-O-caffeoyl-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside]-7-O-beta-D-glucopyranoside (2, calabricoside B). Additionally, seven iridoid and three lignan glycosides were isolated and characterized. Radical scavenging activities of all compounds were determined by quantifying their effects on luminol-enhanced chemiluminescence in formyl-methionyl-leucyl-phenylalanine (FMLP) stimulated human polymorphonuclear neutrophils (PMNs). Calabricoside A and B showed strong radical scavenging activity with IC(50) values of 0.25 and 0.3 microM, respectively.     

Isolation, structure, and synthesis of novel 4-quinolinone alkaloids from Esenbeckia leiocarpa

Two new biocidal quinolinone alkaloids, 3-methoxy-1-methyl-2-propyl-4-quinolone [1] and 2(1'-ethylpropyl)-1-methyl-4-quinolone [2], were efficiently isolated using reversed-phase recycling hplc from the leaves of Esenbeckia leiocarpa. The structures were determined through spectroscopic data and confirmed by total synthesis. These alkaloids have antifeedant activities against the pink bollworm, Pectinophora gossypiella.     

Sesterterpenoids, terretonins A-D, and an alkaloid, asterrelenin, from Aspergillus terreus

Four new sesterterpenoids, terretonins A-D (1-4), and a new alkaloid, asterrelenin (5), together with five known compounds, were isolated from the ethyl acetate extract of a solid-state fermented culture of Aspergillus terreus. Their structures were elucidated on the basis of spectroscopic analysis. The structures of 1, 2, and 5 were confirmed by X-ray crystallographic analysis.     

Cyclic depsipeptides, ichthyopeptins A and B, from Microcystis ichthyoblabe

Bioassay-guided isolation of antiviral compounds from the cultured cyanobacterium Microcystis ichthyoblabe provided two novel cyclic depsipeptides, ichthyopeptins A (1) and B (2). Their structures were determined by 1D (1H and 13C) and 2D (COSY, TOCSY, ROESY, HMQC, and HMBC) NMR spectra, ESIMS-MS, and amino acid analysis. The fraction containing both cyclic depsipeptides exhibited antiviral activity against influenza A virus with an IC50 value of 12.5 microg/mL.