Publications

Biotransformation of 8β-hydroxy-african-4(5)-en-3-one angelate by the fungus Mucor plumbeus afforded as main products 6α,8β-dihydroxy-african-4(5)-en-3-one 8β-angelate and 1α,8β-dihydroxy-african-4(5)-en-3-one 8β-angelate, which had been obtained, together with the substrate, from transformed root cultures of Bethencourtia hermosae. This fact shows that the enzyme system involved in these hydroxylations in both organisms, the fungus and the plant, acts with the same regio- and stereospecificity. In addition another twelve derivatives were isolated in the incubation of the substrate, which were identified as the (2′R,3′R)- and (2′S,3′S)-epoxy derivatives of the substrate and of the 6α- and 1α-hydroxy alcohols, the 8β-(2′R,3′R)- and 8β-(2′S,3′S)-epoxyangelate of 8β,15-dihydroxy-african-4(5)-en-3-one, the hydrolysis product of the substrate, and three isomers of 8β-hydroxy-african-4(5)-en-3-one 2ξ,3ξ-dihydroxy-2-methylbutanoate. The insect antifeedant effects of the pure compounds were tested against chewing and sucking insect species along with their selective cytotoxicity against insect (Sf9) and mammalian (CHO) cell lines.

A new series of hybrid dipeptide‐like organocatalysts based on pyranoid ϵ‐ or ζ‐amino acids and proline have been prepared for the asymmetric Michael addition of aldehydes to β‐nitrostyrenes. The reaction proceeds under mild conditions to afford a wide range of γ‐nitroaldehydes with up to 98% yield and up to 96% ee. These dipeptides are bifunctional organocatalysts, with a proline at the N‐terminus and a carboxylic acid at the C‐terminus. The tetrahydropyran unit embedded in the ϵ‐ or ζ‐amino acid induces a well‐defined conformation that is responsible for the catalysis. These dipeptides represent a new type of organocatalyst with a large number of possibilities to modulate their reactivity and selectivity.

Using a series of standardized sampling plots within forest ecosystems in remote oceanic islands, we reveal fundamental differences between the structuring of aboveground and belowground arthropod biodiversity that are likely due to large-scale species introductions by humans. Species of beetle and spider were sampled almost exclusively from single islands, while soil-dwelling Collembola exhibited more than tenfold higher species sharing among islands. Comparison of Collembola mitochondrial metagenomic data to a database of more than 80 000 Collembola barcode sequences revealed almost 30% of sampled island species are genetically identical, or near identical, to individuals sampled from often very distant geographic regions of the world. Patterns of mtDNA relatedness among Collembola implicate human-mediated species introductions, with minimum estimates for the proportion of introduced species on the sampled islands ranging from 45% to 88%. Our results call for more attention to soil mesofauna to understand the global extent and ecological consequences of species introductions.

In Alzheimer’s disease, the microtubule-associated protein tau forms intracellular neurofibrillary tangles (NFTs). A critical step in the formation of NFTs is the conversion of soluble tau into insoluble filaments. Accordingly, a current therapeutic strategy in clinical trials is aimed at preventing tau aggregation. Here, we assessed altenusin, a bioactive polyphenolic compound, for its potential to inhibit tau aggregation. Altenusin inhibits aggregation of tau protein into paired helical filaments in vitro. This was associated with stabilization of tau dimers and other oligomers into globular structures as revealed by atomic force microscopy. Moreover, altenusin reduced tau phosphorylation in cells expressing pathogenic tau, and prevented neuritic tau pathology induced by incubation of primary neurons with tau fibrils. However, treatment of tau transgenic mice did not improve neuropathology and functional deficits. Taken together, altenusin prevents tau fibrillization in vitro and induced tau pathology in neurons.

A phytochemical study of an extract from transformed root cultures of Nepeta teydea, induced by Agrobacterium rhizogenes, led to the isolation of the following new compounds: the sesquiterpene (-)-cinalbicol, the diterpene teydeadione (6,11,14-trihydroxy-12-methoxy-abieta-5,8,11,13,15-penten-7-one), a degraded C23-triterpene (teydealdehyde) and three fatty acid esters of lanosta-7,24-dien-3β-ol. The propyl ester of rosmarinic acid was also isolated for the first time from a natural source. In addition, two dehydroabietane diterpenes, eight triterpenes and eighteen known phenolic compounds were obtained. The antifeedant, cytotoxic and phytotoxic activities of the isolated compounds have also been investigated.

A highly efficient, diastereoselective, iron(III)‐catalyzed intramolecular hydroamination/cyclization reaction involving α‐substituted amino alkenes is described. Thus, enantiopure trans‐2,5‐disubstituted pyrrolidines and trans‐5‐substituted proline derivatives were synthesized by means of a combination of enantiopure starting materials, easily available from l‐α‐amino acids, with sustainable metal catalysts such as iron(III) salts. The scope of this methodology is highlighted in an enantiodivergent approach to the synthesis of both (+)‐ and (−)‐pyrrolidine 197B alkaloids from l‐glutamic acid. In addition, a computational study was carried out to gain insight into the complete diastereoselectivity of the transformation.

Observations that unequivocally link seismicity and wastewater injection are scarce. Here we show that wastewater injection in eastern Texas causes uplift, detectable in radar interferometric data up to >8 kilometers from the wells. Using measurements of uplift, reported injection data, and a poroelastic model, we computed the crustal strain and pore pressure. We infer that an increase of >1 megapascal in pore pressure in rocks with low compressibility triggers earthquakes, including the 4.8–moment magnitude event that occurred on 17 May 2012, the largest earthquake recorded in eastern Texas. Seismic activity increased even while injection rates declined, owing to diffusion of pore pressure from earlier periods with higher injection rates. Induced seismicity potential is suppressed where tight confining formations prevent pore pressure from propagating into crystalline basement rocks.

Resolving changes in topography through time using accurate high‐resolution digital elevation models (DEMs) is key to understanding active volcanic processes. For the first time in a volcanic environment, we utilize very high‐resolution tri‐stereo optical imagery acquired by the Pleiades‐1 satellite constellation and generate a 1 m resolution DEM of Fogo Volcano, Cape Verde—the most active volcano in the Eastern Atlantic region. Point cloud density is increased by a factor of 6.5 compared to conventional stereo imagery, and the number of 1 m2 pixels with no height measurements is reduced by 43%. We use the DEM to quantify topographic changes associated with the 2014–2015 eruption at Fogo. Height differences between the posteruptive Pleiades‐1 DEM and the preeruptive topography from TanDEM‐X give a lava flow volume of 45.83 ± 0.02 × 106 m3, emplaced over an area of 4.8 km2 at a mean rate of 6.8 m3 s−1.

Over the past twenty-five years, isothermal titration calorimetry (ITC) has become a potent tool for the study a great variety of molecular interactions. This technique is able to provide a complete thermodynamic profile of an interaction process in a single experiment, with a series of advantages in comparison to other comparable techniques, such as less amount of sample or no need of chemical modification or labelling. It is thus not surprising that ITC has been applied to study the manifold types of interactions of natural products to get new insights into the molecular key factors implied in the complexation process of this type of compounds. This review provides an overview over the applications of ITC as a potent tool to investigate interactions of natural products with proteins, nucleic acids, oligosaccharides, and other types of receptors. The examples have been selected depending on the impact that this technique had during the investigation and revision of the interactions involved in the bioactivity of a compound, lead optimization or technical applications.

Investigation of the aerial parts of two Spanish members of the Asteriscus alliance, Asteriscus graveolens subsp. stenophyllus and Asteriscus schultzii, afforded four new sesquiterpene lactones containing a humulene skeleton (1–4) and one new sesquiterpene lactone of the asteriscanolide type (5). Their chemical structures were determined on the basis of the HRMS and from 1D and 2D NMR spectroscopic studies. Both species showed different profiles of sesquiterpenoid constituents. A. schultzii did not show humulene or asteriscane sesquiterpenes, suggesting a resemblance to the genus Pallenis, another member of the Asteriscus alliance. A literature review on chemical isolates from the Asteriscus alliance supported the placement of A. schultzii in the genus Pallenis. The isolated components (1–5) were assessed for cytotoxicity against the HL-60 and MOLT-3 leukemia cell lines, with compound 1 showing activity in both biological assays (IC50 value range 4.1–5.4 μM).