2,2-Dimethylchromenes from Eupatorium aschembornianum

Two new chromenes, eupatoriochromene B and C, and a new benzofuran derivative were isolated from the petrol-soluble fractions of the leaves and flowers of Eupatorium aschembornianum.     

2-Methyl-2-hydroxymethylchromenes from Artemisia campestris subsp. glutinosa

From the non volatile neutral part of a hexane extract from Artemisia campestris subsp. glutinosa, two new 2-methyl-2-hydroxymethyl chromenes h     

Chromenes from ageratina riparia

The reinvestigation of the roots and aerial parts of Ageratina riparia afforded ten new chromenes, their structures being determined by spectral data and chemical transfomrations.     

Distribution of chromenes and benzofurans in Encelia californica

Two populations of Encelia californica (Asteraceae) were analysed for chromenes and benzofurans on an organ specific basis using HPLC. Both classes of compounds were present in all parts of the plant studied including roots, stems, leaves, capitula and achenes. The distribution patterns were less complex in roots and achenes when compared to stems, leaves and capitula which yielded three chromenes and two benzofurans. In addition to the chromenes and benzofurans the capitula afforded a sesquiterpene lactone of the eudesmanolide type which was absent in the other parts of the plant.     

Guaianolides and chromenes from Calea species

Chemical analysis of Calea berteriana yielded, besides the known flavonoid acacetin and the sesquiterpene lactone calbertolide C, three new guaianolides, desacyl-8-tiglylsubcordatolide A and 8-epi-8-tiglylrupicolins A and B. C. prunifolia provided acacetin, calbertolide C, desacyl-8-tiglylsubcordatolide A, and two new chromenes, prunichromenes A and B. From C. solidaginea acacetin, heliangine, calbertolide C, 8-epi-8-tiglylrupicolin A and desacyl-8-tiglylsubcordatolide A were isolated. The structures of the new compounds were established by chemical and spectral methods.     

Quantitative variation of the sesquiterpene lactones and chromenes of encelia farinosa

The components of the two major classes of natural products of the composite Encelia farinosa, sesquiterpene lactones and benzopyrans/benzofurans (chromenes), were resolved and quantified by high performance liquid chromatography. Geographic variation was examined over a range of mesic and xeric populations from California and Arizona (USA). The concentration of farinosin, a sesquiterpene lactone, varies significantly between individuals and seasonally within individuals. Ontogenetic comparisons revealed interpopulation variations within sesquiterpene lactones and chromenes. A geographic survey suggests the presence of two putative chemical races which vary in the amounts of sesquiterpene lactones and chromenes present. The adaptive significance of this quantitative variation is discussed.     

Prenylated benzoic acid derivatives from Piper aduncum L. and P. hostmannianum C. DC. (Piperaceae)

The bioactivity-guided fractionation of the crude extracts from leaves of Brazilian species Piper aduncum and Piper hostmannianum by means of bioautography using the fungi Cladosporium cladosporioides and C. sphaerospermum afforded prenylated methyl benzoate, chromenes, and dihydrobenzopyran derivatives as antifungal compounds. The isolation and structural elucidation of a new compound methyl 4-hydroxy-3-(2′-hydroperoxy-3′-methyl-3′-butenyl)benzoate were performed by application of chromatographic techniques and spectroscopic analyses.     

Metabolism and bioconversion of chromene derivatives inAgeratina adenophora (Asteraceae)

Seedlings ofAgeratina adenophora accumulate the chromenes demethoxyencecalin, encecalin and demethylencecalin. More than 80% of the total chromenes within the seedling are confined to the leaves where they are stored within the mesophyll. Metabolism of the chromenes during development of the seedlings was subjected to analysis by high-performance liquid chromatography. The accumulation kinetics obtained, as well as feeding experiments with non-radioactive chromenes, showed the bioconversion of these compounds to proceed from demethoxyencecalin via hydroxylation yielding demethylencecalin, followed by methylation yielding encecalin. Inhibitor studies with glyphosate indicate that the chromenes arise from precursors derived from the shikimic-acid pathway.Abbreviation HPLC high-performance liquid chromatography     

Synthesis and cytotoxicity evaluation of highly functionalized pyranochromenes and pyranopyrans

A series of fluorinated tetrahydropyrano[3,2-c]chromenes and dihydropyrano[3,2-b]pyran derivatives have been synthesized and their in vitro cytotoxic activities have been determined in cervical cancer cell line (HeLa), human breast adenocarcinoma cell line (MDA-MB-231 and MCF-7) and human alveolar adenocarcinoma cell line (A549). Compounds 4g, 4k, 4p showed a very potent activity against MDA-MB-231, and 4c, 4p showed promising activity against MCF-7, while compounds 4c, 4g, 4p showed moderate activity against HeLa.     

Synthesis and antibacterial activity of some new benzo[5,6]chromeno[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidines

The synthesis and antibacterial activity of some new benzo[5,6]chromeno[2,3-d]pyrimidine derivatives are described. The title compounds were obtained by the reaction of 1H-benzo[f]chromenes with aliphatic and aromatic amines. The structures of all newly synthesized compounds were confirmed by IR, ¹HNMR, ¹³C NMR, and NOESY experiments. The compounds exhibited potent antibacterial activity against gram-positive and gram-negative bacterial species. 10-Methyl-12-(4-hydroxyphenyl)-10,12-dihydro-11H-benzo[5,6]chromeno[2,3-d] pyrimidin-11-imine displayed greater antibacterial activity against gramnegative bacterial species than did ciprofloxacinandamoxicillin.     

Cis-Kolaveninsäure und weitere inhaltsstoffe aus vertretern der tribus eupatorieae

The investigation of further species of the tribe Eupatorieae afforded in addition to already known compounds two new diterpenic acids, three euparine derivatives, two chromenes and two guaianolides closely related to known structures. The results show again the complexity of the tribe; however, some chemotaxonomic lines are visible.     

Deterrent and insecticidal chromenes and benzofurans from Encelia (asteraceae)

Four analogous chromenes and benzofurans that are among the major natural products of the genus Encelia were bioassayed for deterrency and toxicity against pest insects. The chromene encecalin has both antifeedant and insecticidal properties towards larvae of the noctuid pests Peridroma saucia and Plusia gamma. In addition to reducing larval growth and decreasing survivorship of neonate larvae fed artificial diets containing encecalin, this chromene was directly insecticidal to neonate larvae after 4 hr using a residue contact bioassay. Topical application of encecalin to third instar larvae of Peridroma led to a reduction in dietary utilization, indicative of a metabolic cost of handling the compound. The demethyl analogue of encecalin is considerably less active, and the benzofurans euparin and methyleuparin, all common constituents of Encelia, were essentially inactive or only weakly active in all bioassays against the insects.     

Natural products from <Emphasis Type="Italic">Peperomia</Emphasis>: occurrence,biogenesis and bioactivity

The Peperomia is one of the giant genus among Angiosperms with approximately 1600 species spread in the tropics. Their species are valuable as ornamental and several medicinal uses were described but their phytochemistry is poorly investigated compared to Piper (2000 species). In spite of this scarcity, typical classes of secondary metabolites isolated from their species are characterized as polyketides, meroterpenes, chromenes, phenylpropanoids, lignans and amides, among which 2-acylcyclohexane-1,3-diones, orsellinic acid-based meroterpenes and secolignans (peperomins) are very specific to Peperomia. The bioactivities of several compounds indicated their potential as antiparasites, antimicrobial, antiviral, cytotoxic agents against several tumoral strains and also as herbicides.     

Detoxification of naturally occurring chromenes in larvae of the generalist herbivore Spodoptera littoralis (Noctuidae)

Five naturally occurring chromenes from the Asteraceae including the insecticidal compounds precocene II (1) and encecalin (2) were administered to last instar larvae of Spodoptera littoralis via the food or by topical contact. Metabolites formed and excreted via the frass were analysed by GC-MS and by direct comparison with reference compounds obtained by partial synthesis. In total 28 different metabolites were identified, many of them reported here for the first time. All metabolites detected originated from phase I reactions (most probably catalysed by Cytochrom P-450-dependent monooxygenases) by hydroxylation, demethylation or reduction of the parent chromenes. The resulting metabolites can be regarded as detoxification products based on previous structure-activity studies. The increased polarity of the metabolites will furthermore facilitate their excretion by the larvae compared to the more apolar parent chromenes. The largest number of metabolites (eight for each compound) was detected following oral treatment with precocene II and encecalin respectively. 3-Monool as well as 3,4-trans-diol derivatives predominated in the frass of larvae treated with the latter compounds whereas the 6-hydroxyethyl derivatives were the major metabolites of the other chromenes investigated. The patterns of metabolites originating from precocene II or encecalin were the same following oral application or topical treatment.     

Synthesis and antirhinovirus activity of new 3-benzyl chromene and chroman derivatives

A series of 3-benzyl chromenes and chromans were synthesized and tested in vitro against human rhinovirus (HRV) 1B and 14, two representative serotypes for rhinovirus group B and A, respectively. All the new compounds, with the exception of 3-benzyl-2H-chromene (3a), showed a potent activity against HRV serotype 1B within micro or submicromolar range (IC₅₀s from 0.11 to 6.62 μM). The low cytotoxicity of all the derivatives resulted in compounds with high therapeutic index (TI). On the contrary, HRV 14 infection was only weakly inhibited by the majority of these compounds. The 3-benzylidenechromans 2b and 2c showed the highest anti-HRV 1B activity (IC₅₀ 0.12 and 0.11 μM, respectively) coupled with remarkable TI (625.00 and 340.91, respectively). Mechanism of action studies on (Z)-3-(4-chlorobenzylidene)chroman (2b) suggest that the new compounds behave as capsid binders and interfere with very early stages of HRV 1B replication, similarly to related flavanoids.     

Benzopyrans from Hypericum polyanthemum.

From the aerial parts of Hypericum polyanthemum Klotzsch ex Reichardt (Guttiferae), three chromenes, 6-isobutyryl-5,7-dimethoxy-2,2-dimethyl-benzopyran; 7-hydroxy-6-isobutyryl-5-methoxy-2,2-dimethyl-benzopyran and 5-hydroxy-6-isobutyryl-7-methoxy-2,2-dimethyl-benzopyran were isolated. Their structures were determined by NMR spectroscopic analyses.     

Dynamics of the excited states of chromenes studied by fast and ultrafast spectroscopies.

In this paper, the photodynamics of three chromenes (2,2-spiro-adamantyl-7,8-benzo(2H)chromene, 2,2-diphenyl(2H)chromene and 2,2-diphenyl-5,6-benzo(2H)chromene) has been investigated by nano- and femtosecond time resolved techniques in hydrocarbon solutions at room temperature. Using pump-probe techniques, ultrafast steps of molecular dynamics characterizing the photoresponse of chromenes have been investigated: the breakage of the C-O bond was found to occur within a few hundred femtoseconds producing a short-lived transient that converts to the cisoid-cis open form in less than one picosecond and then to the metastable transoid-cis structure within a few picoseconds. The effect of different excitation wavelengths on the formation rate of the first shortest-lived transient of 5,6DPBC is in agreement with the model previously proposed to explain the wavelength dependence of the reaction and emission quantum yields in photostationary experiments. The results obtained in the nanosecond time domain show that the triplet marginally participates in the photoreaction for only one of the studied compounds (2,2-spiro-adamantyl-7,8-benzo(2H)chromene).     

Chromenes from Peperomia serpens (Sw.) Loudon (Piperaceae)

Chromatographic separation of the CH2Cl2 extract from leaves of Peperomia serpens yielded two chromenes [5-hydroxy-8-(3',7'-dimethylocta-2',6'-dienyl)-2,2,7-trimethyl-2H-1-chromene (1) and 5-hydroxy-8-(3'-methyl-2'-butenyl)-2,2,7-trimethyl-2H-1-chromene-6-carboxylic acid (2)], besides the known chromene [methyl 5-hydroxy-2,2,7-trimethyl-2H-1-chromene-6-carboxylate (3)] and the flavonoid, dihydrooroxylin (4). Their structural elucidation were achieved by spectroscopic analyses. The antifungal activities of the CH2Cl2 extract and the isolated chromenes were measured bioautographically against Cladosporium cladosporioides and C. sphaerospermum, when it was found that the crude extract showed higher activity as compared to the pure compounds.     

Chemical variation and defense of Encelia farinosa

Chemical analysis of leaves from 12 different localities of Encelia farinosa (including var. phenicodonta and var. radians) collected on the peninsula of Baja California (Mexico) revealed the presence of various chemotypes that differed with regard to the concentrations of chromenes and sesquiterpene lactones. Localities of E. farinosa collected in the northern part of Baja California were characterized by high concentrations of the chromene encecalin (up to 252 μmol g⁻¹ dry wt.), whereas the sesquiterpene lactone farinosin was not detected. Localities of E. farinosa collected at the southern tip of the peninsula lacked encecalin, but were shown to accumulate farinosin (up to 85 μmol g⁻¹ dry wt.) instead. On the mainland of Mexico, as well as in Arizona (U.S.A.), farinosin concentrations varied from 18 to 44 μmol g⁻¹ dry wt. for 10 different localities analyzed. Chromenes were not detected or present only in minor amounts (up to 13 μmol g⁻¹ dry wt.), when compared to the samples from northern Baja California. Chemical variation within localities was small when compared to variation between different localities. Accumulation of encecalin and aridity seem to coincide at least on the peninsula of Baja California, as localities of E. farinosa that receive the least amount of rainfall contained the largest amounts of encecalin in their leaves. Leaves of E. farinosa that contained sufficiently large amounts of either encecalin or farinosin were both detrimental to neonate larvae of the polyphagous pest insect Spodoptera littoralis as shown by addition of the respective crude leaf extracts to artificial diet. Possible advantages of the observed intraspecific chemical variability of E. farinosa with regard to adaptation by generalist insect herbivores are discussed.     

Chromenes of polyketide origin from Peperomia villipetiola

An extract of leaves and stems of Peperomia villipetiola has been found to contain myristicin (3-methoxy-4,5-methylenedioxy-allylbenzene) and seven chromenes, whose structures are methyl 5-hydroxy-7-methyl-2,2-dimethyl-2H-1-chromene-6-carboxylate (1), methyl 5-methoxy-7-methyl-2,2-dimethyl-2H-1-chromene-8-carboxylate (2), methyl 7-hydroxy-5-methyl-2,2-dimethyl-2H-1-chromene-6-carboxylate (3), methyl 7-methoxy-5-methyl-2,2-dimethyl-2H-1-chromene-6-carboxylate (4), 5-methanol-7-hydroxy-2,2-dimethyl-2H-1-chromene-6-carboxylic acid (5), 5-methanol-7-methoxy-2,2-dimethyl-2H-1-chromene-6-carboxylic acid (6), and methyl 5-acetoxymethanol-7-hydroxy-2,2-dimethyl-2H-1-chromene-6-carboxylate (7). A biosynthetic rationale for 1-7 suggests that orsellinic acid may be a common intermediate. The anti-fungal activities of the chromenes were measured bioautographically against Cladosporium cladosporioides and Cladosporium sphaerospermum: compounds 6 and 7 were found to be the most active.