Bond reactivity indices approach analysis of the [2+2] cycloaddition of jatrophane skeleton diterpenoids from Euphorbia gaditana Coss to tetracyclic gaditanone.

The reaction mechanism of the intramolecular [2 + 2] cycloaddition from a jatrophane precursor to the gaditanane skeleton, an unprecedented 5/6/4/6-fused tetracyclic ring framework recently isolated from Euphorbia spp., was studied using the bond reactivity indices approach. Furthermore, six diterpenoids, including three undescribed jatrophanes isolated from E. gaditana Coss, were described. The structures of these compounds were deduced by a combination of 2D NMR spectroscopy and ECD data analysis.

Phytotoxic activity and metabolism of Botrytis cinerea and structure-activity relationships of isocaryolane derivatives.

Research has been conducted on the biotransformation of (8S,9R)-isocaryolan-9-ol (4a) and (1S,2S,5R,8S)-8-methylene-1,4,4-trimethyltricyclo[6.2.1.0(2,5)]undecan-12-ol (5a) by the fungal phytopathogen Botrytis cinerea. The biotransformation of compound 4a yielded compounds 6-9, while the biotransformation of compound 5a yielded compounds 10-13. The activity of compounds 4a and 5a against B. cinerea has been evaluated. (8R,9R)-Isocaryolane-8,9-diol (6), a major metabolite of compound 4a, shows activity compared to its parent compound 4a, which is inactive. The effect of isocaryolanes 3, 4a, and 5a, together with their biotransformation products 6-8, 10, and 14-17, on the germination and radicle and shoot growth of Lactuca sativa (lettuce) has also been determined. Compounds 7-13 are described for the first time.

Biotransformation of clovane derivatives. Whole cell fungi mediated domino synthesis of rumphellclovane A.

Here we describe the biotransformation of clovane derivatives by filamentary fungi Pestalotiopsis palustris and Penicillium minioluteum, and the application of the latter to the synthesis and determination of the absolute configuration of rumphellclovane A (2). Methoxyclovanol (1), a growth inhibitor of the phytopathogen Botrytis cinerea, is metabolised by P. palustris to yield rumphellclovane A (2), a natural compound recently isolated from the gorgonian coral Rumphella antipathies, two new compounds, (1R,2S,5S,8R,9S,10R)-2-methoxyclovane-9,10-diol (5) and (1S,2S,5S,7R,8R,9R)-2-methoxyclovane-7,9-diol (6), hydroxylated in positions not easily accessed by classic synthetic chemistry, and clovanodiols 3 and 4. P. minioluteum is able to selectively transform methoxyclovanol (1) into clovanodiols 3 and 4 and, in turn, lactone 8, the putative intermediate in the above mentioned synthesis of rumphellclovane A (2), into compound 2 via a domino process. The ability of P. minioluteum to carry out the cleavage of ethers on clovane derivatives is also evaluated.

Biotransformation of bioactive isocaryolanes by Botrytis cinerea.

The metabolism of the fungistatic agent (8R,9R)-8-methoxyisocaryolan-9-ol (4) by the fungus Botrytis cinerea has been investigated. Biotransformation of compound 4 yielded compounds 5 and 6-9. No dihydrobotrydial is observed after 4 days of incubation of compound 4. Separate biotransformation of (8R,9R)-isocaryolane-8,9-diol (5) yielded compounds 7-11. The evaluation of the fungistatic activity against B. cinerea of compounds 4, 5, and 6 is reported. (4R,8R,9R)-8-Methoxyisocaryolane-9,15-diol (6), a major metabolite of (8R,9R)-8-methoxyisocaryolan-9-ol (4), shows a much reduced biological activity when compared with the parent compound. Isocaryolane derivatives 6-11 are described for the first time.

Effects of diterpenes from latex of Euphorbia lactea and Euphorbia laurifolia on human immunodeficiency virus type 1 reactivation.

The persistence of latent HIV-infected cellular reservoirs represents the major hurdle to virus eradication in patients treated with highly active antiretroviral therapy, referred to as HAART. HIV-1 reservoirs are long-lived resting CD4+ memory cells containing the virus latently integrated. Since the HIV-1 reservoirs are not targeted by HAART, reactivation therapy has been suggested to purge viral latency. Bioassay-guided study of an ethyl acetate extract of Euphorbia laurifolia afforded two isomeric diterpenes that showed differential activity over HIV-1 reactivation. A previously reported compound was isolated too from Euphorbia lactea. This compound showed a potent HIV-1 reactivating effect. Bioassays results showed that HIV-1 reactivation activity is influenced by distinct structural characteristics.

Sesquiterpenes from the wood of Juniperus lucayana.

Bioassay-guided fractionation of ethanolic extract from the wood of Juniperus lucayana afforded three sesquiterpenes named 3-hydroxypseudowiddran-6(7)-en-4-ol (1), 15-hydroxyallo-cedrol (2) and 12-hydroxywiddrol (3) together with six known sesquiterpenes (4-9) and two known flavonoids (10 and 11). Their structures were established on the basis of comprehensive spectroscopic analyses, including 2D NMR spectroscopy and mass spectrometry. The structures of compounds were identified as 1alpha,4beta,11alpha,11beta-tetramethylbicyclo[5,4,0]undec-6(7)-en-3alpha, 4alpha-diol (1), 4beta-hydroxymethyl-5,5,9beta-trimethyltricyclo[4.3.0.2(1.4)]undecan-3alpha-ol (2) and 4beta-hydroxymethyl-7alpha,11alpha,11beta-trimethylbicyclo [5.4.0]undec-1-en-4alpha-ol (3). The major compounds isolated were evaluated for their antifungal activity against Botrytis cinerea. Widdrol (7) was the most active, reaching the 71% inhibition level on mycelial growth after 6 days.

Quantitative structure-activity relationship studies for the prediction of antifungal activity of N-arylbenzenesulfonamides against Botrytis cinerea.

The Botrytis cinerea is one of the most interesting fungal pathogens. It can infect almost every plant and plant part and cause early latent infections which damage the fruit before ripening. The QSAR is an alternative method for the research of new and better fungicides against B. cinerea. This paper describes the results of applying a topological sub-structural molecular design (TOPS-MODE) approach for predicting the antifungal activity of 28 N-arylbenzenesulfonamides. The model described 86.1% of the experimental variance, with a standard deviation of 0.223. Leave-one-out and leave-group-out cross validation was carried out with the aim of evaluating the predictive power of the model. The values of their respective squared correlations coefficients were 0.754 and 0.741. The TOPS-MODE approach was compared with three other predictive models, but none of these could explain more than 72.8% of the variance with the same number of variables. In addition, this approach enabled the assessment of the contribution of different bonds to antifungal activity, thereby making the relationships between structure and biological activity more transparent. It was found that the fungicidal activity of the chemicals analyzed was increased by the presence of a sulfonamide group bonded to two aromatics rings, making this group the most important of the molecule. The majority of the substituents present in the aromatic rings have an electron withdrawing effect and they contribute to a smaller degree than the sulfonamide group to the property under study. The aromatic moiety plays an important role in this activity; its contribution changes with different substituents. Generally, the nitro group has a positive and great contribution to the biological property but when this group is involved in some compounds in ortho effect with the SO2 moiety of the sulfonamide group a lower value of contribution is observed for both groups.

The antifungal activity of widdrol and its biotransformation by Colletotrichum gloeosporioides (penz.) Penz. & Sacc. and Botrytis cinerea Pers.: Fr.

Widdrol (1) was tested against the necrotrophic plant pathogens Botrytis cinerea and Colletotrichum gloeosporioides. While 1 was found to be inactive against C. gloeosporioides, it showed a selective and effective control of B. cinerea, significantly inhibiting the mycelial growth of the fungus at concentrations of 100 ppm and above. In addition, the biotransformation of 1 by both fungi was studied. Incubation with C. gloeosporioides and B. cinerea afforded four and one biotransformation products (2-6), respectively. Biotransformation with C. gloeosporioides was highly regioselective, yielding for the most part oxidation products at C-10: 10-oxowiddrol (2), 10beta-hydroxywiddrol (3), 10alpha-hydroxywiddrol (4), and 14alpha-hydroxywiddrol (5). The structures of all products were determined on the basis of their spectroscopic data, including coupling constants, two-dimensional NMR analysis (heteronuclear multiple quantum coherence, heteronuclear multiple bond correlation, and nuclear Overhauser enhancement spectroscopy), and nuclear Overhauser effect. The biotransformation products were then tested against B. cinerea and found to be inactive. These results shed further light on the structural modifications, which may be necessary to develop selective fungal control agents against B. cinerea.