Chirality plays a fundamental role in nature, but its detection and quantification still face many limitations. To date, the enantiospecific analysis of mixtures necessarily requires prior separation of the individual components. The simultaneous enantiospecific detection of multiple chiral molecules in a mixture represents a major challenge, which would lead to a significantly better understanding of the underlying biological processes; for example, via enantiospecifically analysing metabolites in their native environment. Here, we report on the first in situ enantiospecific detection of a thirty‐nine‐component mixture. As a proof of concept, eighteen essential amino acids at physiological concentrations were simultaneously enantiospecifically detected using NMR spectroscopy and a chiral solvating agent. This work represents a first step towards the simultaneous multicomponent enantiospecific analysis of complex mixtures, a capability that will have substantial impact on metabolism studies, metabolic phenotyping, chemical reaction monitoring, and many other fields where complex mixtures containing chiral molecules require efficient characterisation.

The concept of multiple-FID acquisition (MFA) within the same scan is applied to acquire simultaneously multiple 2D spectra from a single NMR experiment. A discussion on the incorporation of the MFA strategy in homonuclear and heteronuclear pulse sequences is presented. Several novel COSY- and HMBC-type experiments are reported as a time-efficient solution in small-molecule NMR spectroscopy.

A dual NMR data acquisition strategy to handle and detect two active equivalent transfer pathways is presented and discussed. We illustrate the power of this time-efficient approach by collecting two different 2D spectra simultaneously in a single experiment: i) TOCSY or HSQC-TOCSY spectra with different mixing times, ii) F2-13 C-coupled and decoupled HSQC spectra, iii) conventional and pure-shift HSQC spectra, or iv) complementary HSQC and HSQC-TOCSY spectra.The overall experimental time of a 2D NMR experiment is defined fundamentally by the imposition of extended recycle delays for a proper T 1 relaxation, of an enough number of recorded t 1 increments to achieve an optimum resolution in the indirect F1 dimension and/or of a minimum number of scans per t 1 increment required to complete a phase cycle for efficient coherence transfer pathways (CTP) selection. This situation is commonly found in modern NMR applications on small molecules, where some milligrams of sample are often more than enough to run the most basic experiments in short experimental times. Possible solutions to economize spectrometer time could be the attempt to speed up data acquisition by some fast NMR method, including shortening the recycle delay, the collection of a moderate number of t 1 increments or the efforts to reduce the needs of long phase cycles by using pulsed field gradient (PFG) CTP selection. Another option relies on the acquisition of multiple NMR spectra using a single pulse sequence which can offer attractive benefits regarding simplicity, efficiency, automation and, in some cases, improved sensitivity per time unit. Some examples of this multiple data acquisition strategy include the collection of multiple FIDs within the same scan (MFA), [1][2][3] the recent concept of NOAH based on the interleaved acquisition of various experiments to avoid long recycle delays, [4,5] the simultaneous acquisition of equivalent 13 C and 15 N spectra by time-sharing NMR spectroscopy, [6] or the use of multiple receivers to detect different nuclei in a parallel or interleaved manner. [7] The simultaneous acquisition of multiple spectra is particularly useful when dealing on complementary NMR experiments having comparable sensitivity (requiring similar scans per t 1 increments, similar phase cycling), resolution (similar number of t 1 increments) and/or performance (similar parameters settings, the same acquisition mode…) requirements. The success of these timeefficient methods depends on which is the best multiple acquisition strategy (parallel, interleaved, afterglow, separate…) regarding sensitivity, performance and/or spectrometer time savings.On the other hand, NMR pulse sequences usually monitor a specific CTP by an appropriate phase cycle or PFG coherence selection procedure. However, some sequences have been designed to exploit several CTPs at the same time. A very representative example is the so-called Preservation of Equivalent Pathways (PEP) technique which has been used to add up two different co-existing magnetization components...

The detection of ultra-long-range ( 4 J CH and higher) heteronuclear connectivities can complement the conventional use of HMBC/HSQMBC data in structure elucidation NMR studies of proton-deficient natural products, where two-bond and three-bond correlations are usually observed. The performance of the selHSQMBC experiment with respect to its broadband HSQMBC counterpart is evaluated. Despite its frequency-selectivity nature, selHSQMBC efficiently prevents any unwanted signal phase and intensity modulations due to passive proton−proton coupling constants typically involved in HSQMBC. As a result, selHSQMBC offers a significant sensitivity enhancement and provides pure in-phase multiplets, improving the detection levels for short-and long-range cross-peaks corresponding to small heteronuclear coupling values. This is particularly relevant for experiments optimized to small n J CH values (2−3 Hz), referred to as LR-selHSQMBC, where key cross-peaks that are not visible in the equivalent broadband LR-HSQMBC spectrum can become observable in optimum conditions.

As part of our search for bioactive metabolites from understudied marine microorganisms, the new chlorinated metabolite chlovalicin B (1) was isolated from liquid cultures of the marine basidiomycete Digitatispora marina, which was collected and isolated from driftwood found at Vannøya, Norway. The structure of the novel compound was elucidated by spectroscopic methods including 1D and 2D NMR and analysis of HRMS data, revealing that 1 shares its molecular scaffold with a previously isolated compound, chlovalicin. This represents the first compound isolated from the Digitatispora genus, and the first reported fumagillin/ovalicin-like compound isolated from Basidiomycota. Compound 1 was evaluated for antibacterial activities against a panel of five bacteria, its ability to inhibit bacterial biofilm formation, for antifungal activity against Candida albicans, and for cytotoxic activities against malignant and non-malignant human cell lines. Compound 1 displayed weak cytotoxic activity against the human melanoma cell line A2058 (~50% survival at 50 µM). No activity was detected against biofilm formation or C. albicans at 50 µM, or against bacterial growth at 100 µM nor against the production of cytokines by the human acute monocytic leukemia cell line THP-1 at 50 µM.