Computational Approaches and Use of Chiroptical Probes in the Absolute Configuration Assignment to Natural Products by ECD Spectroscopy: A 1,2,3-Trihydroxy-p-menthane as a Case Study

In this study, the computational analysis of electronic circular dichroism (ECD) spectra and the employment of biphenyl chiroptical probes were compared in the absolute configuration assignment of (-)-1 proportional to,2 proportional to,3 beta-trihydroxy-p-menthane (1), taken as a representative example of a UV-transparent chiral natural product. The usefulness of chiroptical probes in the configurational assignments of natural products and their complementarity to the computational protocols is herein highlighted. The biphenyl probe approach proves to be straightforward, reliable, and suitable for conformationally mobile and ECD silent compounds, not treatable by computational analysis of chiroptical data

Diplofuranoxin, a disubstituted dihydrofuranone, was produced together with sphaeropsidin A and epi-sphaeropsidone by Diplodia subglobosa, an emerging ash (Fraxinus excelsior L.) pathogen in Europe

An undescribed disubstituted dihydrofuranone, named diplofuranoxin, was isolated, together with the six well known metabolites sphaeropsidins A and C, epi-sphaeropsidone, mellein and cis- and trans-4-hydroxymelleins, from the fungal species Diplodia subglobosa, an emerging pathogen involved in the ash dieback aetiology in Europe. Currently, the disease represents the main threat to European ash heritage and the wood associated industry. Diplofuranoxin, was characterized essentially by NMR and HRESIMS spectra as (3Z)-3-(2,3-dihydrox-ybutylidene)-5-methyldihydrofuran-2(3H)-one. Its relative and absolute configuration was determined by joining NOESY NMR experiments and computational analysis of electronic circular dichroism spectrum. All the metabolites were screened for phytotoxic, antioomycetes and zootoxic activities and only sphaeropsidin A and epi-sphaeropsidone were active in two out of three bioassays performed. In addition, sphaeropsidin A completely inhibited mycelium growth of Phytophthora cambivora, whereas the inhibition rate of epi-sphaeropsidone was less than 50% at the higher concentration used. Both metabolites were inactive in the Artemia salina assay. Results obtained in this study have allowed to characterize for the first time the main metabolites produced in vitro by D. subglobosa and to increase the knowledge on the metabolic profile of Botryosphaeriaceae for a correct taxo-nomic classification of the strains belonging to this family

Palladium Complexes of N-Methylcorroles

Alkylation of one of the inner-core nitrogen atoms is one possible approach to obtain dianionic corrole ligands, suitable for the coordination of divalent metal ions, such as Pd-II. Inner-core N-methylation can be obtained by treating the corrole with CH3I, but the reaction conditions should be optimized to limit the formation of the dimethylated derivative. Two regioisomers, the N-21 and the N-22 methyl derivatives are obtained from the reaction, with the first product achieved in a higher amount. Structural characterization of the reaction products evidenced the distortion induced by the introduction of the methyl groups; the N-methylcorroles are chiral compounds, and the enantiomers were separated by chromatography, with their absolute configuration assigned by ECD computation. Palladium insertion was achieved in the case of monosubstituted corroles, but not with the dimethylated macrocycle; X-ray characterization of the complexes showed the distortion of the macrocycles. The Pd complexes do not show luminescence emission, but are able to produce singlet oxygen upon irradiation. The Pd-II complexes were also inserted in human serum albumin (HSA) and dispersed in water; in this case, the protein protects the corroles from photobleaching, and a switch from the type II to the type I mechanism in reactive oxygen species (ROS) production is observed