Structure and Anti-TB Activity of Trachylobanes from the Liverwort Jungermannia exsertifolia ssp. cordifolia

In the critical search for new antituberculosis lead compounds, bryophytes represent a largely untapped resource of chemically diverse structures. From the liverwort Jungermannia exsertifolia subsp. cordifolia, 11 new trachylobane diterpene derivatives, as well as three known compounds, were isolated. Their structures were elucidated by spectroscopic means, and full 1H NMR spin analysis of one model compound confirmed the relative configurational assignments of the congeners. Four of the isolates exhibited noticeable activity against virulent Mycobacterium tuberculosis H37Rv with minimal inhibitory concentrations of 61−24 μg/mL. This finding suggests that bryophytes in general and trachylobanes in particular deserve further attention in the search for new antimycobacterial leads

2D NMR barcoding and differential analysis of complex mixtures for chemical identification: The Actaea triterpenes

The interpretation of NMR spectroscopic information for structure elucidation involves decoding of complex resonance patterns that contain valuable molecular information (\u3b4 and J), which is not readily accessible otherwise. We introduce a new concept of 2D-NMR barcoding that uses clusters of fingerprint signals and their spatial relationships in the \u3b4-\u3b4 coordinate space to facilitate the chemical identification of complex mixtures. Similar to widely used general barcoding technology, the structural information of individual compounds is encoded as a specifics pattern of their C,H correlation signals. Software-based recognition of these patterns enables the structural identification of the compounds and their discrimination in mixtures. Using the triterpenes from various Actaea (syn. Cimicifuga) species as a test case, heteronuclear multiple-bond correlation (HMBC) barcodes were generated on the basis of their structural subtypes from a statistical investigation of their \u3b4H and \u3b4C data in the literature. These reference barcodes allowed in silico identification of known triterpenes in enriched fractions obtained from an extract of A. racemosa (black cohosh). After dereplication, a differential analysis of heteronuclear single-quantum correlation (HSQC) spectra even allowed for the discovery of a new triterpene. The 2D barcoding concept has potential application in a natural product discovery project, allowing for the rapid dereplication of known compounds and as a tool in the search for structural novelty within compound classes with established barcodes. \ua9 2014 American Chemical Society.Peer reviewed: YesNRC publication: Ye

Toward Structural Correctness: Aquatolide and the Importance of 1D Proton NMR FID Archiving

The revision of the structure of the sesquiterpene aquatolide from a bicyclo[2.2.0]hexane to a bicyclo[2.1.1]hexane structure using compelling NMR data, X-ray crystallography, and the recent confirmation via full synthesis exemplify that the achievement of "structural correctness" depends on the completeness of the experimental evidence. Archived FIDs and newly acquired aquatolide spectra demonstrate that archiving and rigorous interpretation of 1D H-1 NMR data may enhance the reproducibility of (bio)chemical research and curb the growing trend of structural misassignments. Despite being the most accessible NMR experiment, 1D H-1 spectra encode a wealth of information about bonds and molecular geometry that may be fully mined by H-1 iterative full spin analysis (HiFSA). Fully characterized 1D H-1 spectra are unideterminant for a given structure. The corresponding FIDs may be readily submitted with publications and collected in databases. Proton NMR spectra are indispensable for structural characterization even in conjunction with 2D data. Quantum interaction and linkage tables (QuILTs) are introduced for a more intuitive visualization of 1D J-coupling relationships, NOESY correlations, and heteronuclear experiments. Overall, this study represents a significant contribution to best practices in NMR-based structural analysis and dereplication

Distinguishing vaccinium species by chemical fingerprinting based on NMR spectra, validated with spectra collected in different laboratories

A method was developed to distinguish Vaccinium species based on leaf extracts using nuclear magnetic resonance spectroscopy. Reference spectra were measured on leaf extracts from several species, including lowbush blueberry (Vaccinium angustifolium), oval leaf huckleberry (Vaccinium ovalifolium), and cranberry (Vaccinium macrocarpon). Using principal component analysis, these leaf extracts were resolved in the scores plot. Analysis of variance statistical tests demonstrated that the three groups differ significantly on PC2, establishing that the three species can be distinguished by nuclear magnetic resonance. Soft independent modeling of class analogies models for each species also showed discrimination between species. To demonstrate the robustness of nuclear magnetic resonance spectroscopy for botanical identification, spectra of a sample of lowbush blueberry leaf extract were measured at five different sites, with different field strengths (600 versus 700MHz), different probe types (cryogenic versus room temperature probes), different sample diameters (1.7mm versus 5mm), and different consoles (Avance I versus Avance III). Each laboratory independently demonstrated the linearity of their NMR measurements by acquiring a standard curve for chlorogenic acid (R2=0.9782 to 0.9998). Spectra acquired on different spectrometers at different sites classifed into the expected group for the Vaccinium spp., confirming the utility of the method to distinguish Vaccinium species and demonstrating nuclear magnetic resonance fingerprinting for material validation of a natural health product.Peer reviewed: YesNRC publication: Ye