Antibacterial diterpenoids from Cedrus atlantica.

Four diterpene alcohols were isolated from the neutral hexane extract of the cones of Cedrus atlantica, and their structures were confirmed after comparing their spectral data with literature values. These products exhibited significant antibacterial activity against gram (+/-) bacteria.

Germacranolides from Anvillea radiata.

The aerial parts of Anvillea radiata yielded a new germacranolide, 8alpha,9alpha-epoxyparthenolide (3), together with two known compounds, 9alpha-hydroxyparthenolide (1) and parthenolid-9-one (2). The structures of the compounds were elucidated from IR, HRMS, 1H and 13C-NMR, COSY, HETCOR, HMBC and HOHAHA spectral data. The major component 1 was tested for its cytotoxicity and antibacterial activity.

Improved GA1 production by Fusarium fujikuroi.

Recent studies into gibberellin A(1) (GA(1)) showed it to be physiologically more active than GA(3) in plants of great agricultural interest, such as tomatoes, rice, peas, and sweet cherries. We describe here a simple procedure for obtaining large quantities of GA(1) (1,500 mg/l) by incubating the FKMC1995 strain of Fusarium fujikuroi in a standard complex medium (SCM). We also compare the GA production of this strain with that of two other wild-type strains of F. fujikuroi (IMI58289, m567) in SCM and low-nitrogen medium and discuss the possible biogenetic mechanisms involved in the over-accumulation of GA(1) by FKMC1995.

Atividade antibacteriana de furanoeliangólidos / Antibacterial activity of furanoeliangolides

As lactonas sesquiterpênicas licnofólido (1) e eremantólido C (2) e alguns derivados: 1 ,2 -epóxieremantólido C (3), 1 β -hidróxi-2,3-diidroeremantólido C (4), 3 - hidróxieremantólido C (5), cloreto de 4,5-diidroeremantólido-5-n-propilamônio (6) e 1 β -hidróxi- 2,3-diidrolicnofólido (7) foram testadas contra as bactérias Enterococus faecalis S48, Bacillus subtilis CECT 397, Staphylococus aureus ATCC 8, Salmonella typhymurium LT2, Escherichia coli U9 e Proteus sp. Os compostos 1, 4, 5 e 7 apresentaram atividade antibacteriana.

Sesquiterpene lactones lychnopholide (1) and eremantholide C (2) and some derivatives: 1 ,2 -epoxyeremantholide C (3), 1 β -hidroxy-2,3-dihydroeremantolide C (4), 3 -hydroxyeremantholide C (5), 5-n- propylamonium- 4,5-dihydroeremantholide C chloride (6) and 1 β -hydroxy-2,3- dihydrolychnopholide (7) were tested against Enterococus faecalis S48, Bacillus subtilis CECT 397, Staphylococus aureus ATCC 8, Salmonella typhymurium LT2, Escherichia coli U9 e Proteus sp. Compounds 1, 4, 5 and 7 showed activity.

Microbial transformation of ent-kaurenoic acid and its 15-hydroxy derivatives by the SG138 mutant of Gibberella fujikuroi.

Feeding experiments with ent-kaurenoic acid (4), 15 alpha-hydroxy-ent-kaurenoic acid (5), 15 beta-hydroxy-ent-kaurenoic acid (6), and mixtures of 4 plus 5 and 4 plus 6 were conducted using the SG138 mutant of Gibberella fujikuroi, to gain information about the phenotype of this unique strain. The biotransformation of 5 gave 7 beta,15 alpha-dihydroxykaurenolide (9) and 7 beta,15 alpha-dihydroxy-ent-kaurenoic acid (13). The incubation of 6 produced 7 beta,15 beta-dihydroxy-ent-kaurenoic acid (7) and 7 beta,15 beta-dihydroxykaurenolide (10). No 15-hydroxylated gibberellins were detected in any of these experiments. The results indicated that a hydroxy group at C-15 does not inhibit 7 beta-hydroxylase activity but in the SG138 strain obstructs the enzymatic ring-B contraction of ent-kaurenoids to gibberellins. Exogenous 4 stimulated both the excretion of ent-kaurene and the fungal metabolism of 5 and 6.

Approach to the synthesis of antitumor quassinoids from labdane diterpenes: an efficient synthesis of a picrasane-related intermediate.

[structure: see text]. The tetracyclic ketal 24, a suitable intermediate for the synthesis of antitumor pentacyclic quassinoids, has been efficiently prepared from communic acids (5a-c), via methyl ketone 9. The synthetic sequence from 9 to 24 consists of 15 steps in 12% overall yield.

A novel alkaloid serantrypinone and the spiro azaphilone daldinin D from Penicillium thymicola.

The novel quinazoline metabolite serantrypinone (1) has been isolated from an isolate of the microfungus Penicillium thymicola together with daldinin D (2), a new peracetylated spiro azaphilone derivative. The structures of 1 and 2 were elucidated by analysis of spectroscopic data, including 2D NMR, and comparison with literature data.

Saikosaponins from roots of Bupleurum gibraltaricum and Bupleurum spinosum.

Two new saikosaponins have been identified in the butanolic fraction of the ethanol extract of the roots of Bupleurum spinosum: 3beta,16alpha,23,28-tetrahydroxyoleana-11,13(18)-dien- 30-oic acid 3-O-beta-D-glucopyranosyl-(1 --> 2)-beta-D-glucopyranosyl-(1 --> 3)-beta-D-fucopyranoside, and 3beta,16alpha,23,28,30-pentahydroxyoleana-11,13(18)-diene 3-O-beta-D-glucopyranosyl-(1 --> 2)-beta-D-glucopyranosyl-(1 --> 3)-beta-D-fucopyranoside. 3Beta,16beta,23-trihydroxy-13,28-epoxyolean-11-ene 3-O-beta-D-glucopyranosyl-(1 --> 2)-beta-D-glucopyranosyl-(1 --> 3)-beta-D-fucopyranoside was also isolated, and this structure agreed with the one proposed for bupleuroside I, but their spectroscopic data have not been described until now. From the same fraction of the roots of Bupleurum gibraltaricum, the known compound buddlejasaponin IV has been isolated as the predominant component (90%). Structures were elucidated using spectroscopic analysis, specially 2D-NMR experiments.

Natural and synthetic podolactones with potential use as natural herbicide models.

A collection of 11 natural and synthetic podolactones have been tested as allelochemicals in a range between 10(-4) and 10(-9) M, and their potential use as natural herbicide models is discussed. Their effects on the germination and growth of the dicots Lactuca sativa (cv. Nigra and cv. Roman), Lepidium sativum, and Lycopersicon esculentum and the monocots Allium cepa, Hordeum vulgare, and Triticum aestivum as standard target species have been studied. An important inhibitory effect on the germination and growth of all tested species (average = 90%) was produced by compounds 9-11 at 10(-4) M. The specific structural requirements related to their activities are studied. On the basis of these results, their use as potential natural herbicide models is proposed.

Microbial hydroxylation/functionalization of terpenoid synthons derived from communic acids.

Incubation of a communic acid-derived synthon with Cunninghamella elegans quantitatively affords 1 beta, 3 beta- and 7 beta- monohydroxylated derivatives.

Longipinene derivatives from Santolina viscosa.

The neutral fraction of the hexane extract of the aerial parts of Santolina viscosa afforded eight new longipinene derivatives (1-8), oblongifolidiol (9), and several other known compounds. The structures of 1-8 were established by spectroscopic methods and chemical transformations. The vulgarone A-type structure previously reported for oblongifolidiol has been reassigned as the longipinene derivative 9 using 2D NMR, chemical correlations, and X-ray diffraction.

Preparation, stereochemistry, and cytotoxic activity of the melampolides from Mikania minima.

The semisyntheses of melampolides 1 and 2, previously found in Mikania minima, were carried out in order to confirm their chemical structures and to establish their absolute configurations. Their conformational analyses, performed using molecular mechanics, experimental (1)H NMR coupling constants, and NOE experiments, showed a preferred DU conformer in solution at room temperature. The cytotoxic activities of 1 and 2 against three tumor cell lines were also determined. Conjugated aldehyde 2 showed higher activity than alcohol 1.

New sources and antifungal activity of sesquiterpene lactones.

In the search for new sources of sesquiterpene lactones, six Centaurea species have been analyzed. The activity against the fungus Cunninghamella echinulata of (+)-cnicin (1) and (+)-salonitenolide (2), isolated from the Centaurea plants, as well as that of (+)-costunolide (3), (-)-dehydrocostuslactone (4), (-)-lychnopholide (5) and (-)-eremantholide C (6), has been evaluated. Compounds 3 and 4 showed noticeable EC50 values, whilst more polar lactones were inactive. These results suggest that a relatively low polarity is one of the molecular requirements for the antifungal activity of sesquiterpene lactones.

Synthesis of 11,12-epoxydrim-8,12-en-11-ol, 11,12-diacetoxydrimane, and warburganal from (-)-sclareol.

The first syntheses are reported for recently isolated drimanes 11, 12-epoxydrim-8,12-en-11-ol (2) and 11,12-diacetoxydrimane (3), from (-)-sclareol (1). Furthermore, two efficient new routes to the potent bioactive warburganal (4) starting also from 1 are described.

Synthesis and antitumoral activities of marine ent-chromazonarol and related compounds.

Efficient syntheses of ent-isozonarol (6a), ent-isozonarone (7a) and ent-chromazonarol (8) from (-)-sclareol (12) are described. 6a and 7a show a significative antitumoral activity.

Bioactive sesquiterpenes from Santolina rosmarinifolia subsp. Canescens. A conformational analysis of the germacrane ring.

The hexane extract of aerial parts of Santolina rosmarinifolia subsp. canescens afforded eight new sesquiterpenes in addition to known compounds. Their structures were determined by spectroscopic methods and chemical transformations. The conformational analysis of the germacrane constituents was carried out by spectroscopic methods, including NMR at varying temperature and by molecular mechanics calculations. The antifeedant, antibacterial and antitumoral activity of selected compounds has been tested.

Phycomysterols and other sterols from the fungus Phycomyces blakesleeanus.

In the search for novel bioactive products from filamentous fungi, sterols and triterpenoids found in Phycomyces blakesleeanus were analyzed using semipreparative HPLC, GC-MS, and NMR techniques. Structures proposed for the three new compounds identified, phycomysterol A (1), phycomysterol B (2), and neoergosterol (3), were confirmed by chemical synthesis. Phycomysterols possess a new natural 19-norergostane skeleton with an aromatic B ring. Phycomysterol A showed anti-HIV activity.

Mutants of phycomyces with decreased gallic acid content.

Most plants and some fungi accumulate phenols. Two hydroxybenzoic acids, gallic and protocatechuic acids, are abundant in the giant sporangiophores of the zygomycete Phycomyces blakesleeanus, much more so than in the basal mycelium or the culture medium. The actual concentrations vary with illumination, age of the culture, and composition of the medium. We devised a simple screening procedure to isolate hba mutants whose sporangiophores contained less gallic acid than the wild type. The most useful mutant had very low concentrations of hydroxybenzoic acids in the sporangiophores, but about the same as the wild type in the basal mycelium and the medium. The mutant was only slightly different from the wild type in growth and morphology. Mutant and wild-type sporangiophores grew away from ultraviolet C sources (260 nm) equally well. Contrary to previous conjectures, ultraviolet tropism does not depend on the ultraviolet absorption of gallic acid or other free hydroxybenzoic acids in the sporangiophore. Against expectations, phenols did not impair DNA extraction: sporangiophores produced better DNA preparations than basal mycelia and the hba mutant only slightly better than the wild type.

Biomimetic cyclization of cnicin to malacitanolide, a cytotoxic eudesmanolide from Centaurea malacitana.

Malacitanolide (2), a new eudesmanolide isolated from the aerial parts of Centaurea malacitana, was characterized spectroscopically. The synthesis of 2 from cnicin (1), via the epoxide 3, confirmed the structure and stereochemistry of malacitanolide, as well as its biogenetic relationship with 1. Cytotoxic activity values for 2 are significantly higher than for 1.