Computer-assisted Structure Elucidation Methods Research Articles

Three Unusual Sesquiterpenes with Distinctive Ring Skeletons from Daphne penicillata Uncovered by Molecular Networking Strategies

Daphnenoids A-C (1-3), three unusual sesquiterpenes with distinctive ring skeletons, together with a biogenetically related daphnenoid D (4) were obtained from the herb of Daphne penicillata by molecular networking strategies. Daphnenoid A (1) possesses a unique caged tetracyclo [5.3.2.01,6.04,11] dodecane scaffold by unexpected cyclizations of C-1/C-11 and C-2/C-14. Daphnenoids B and C (2 and 3) were the first discovered natural sesquiterpenes with unique 5/5 spirocyclic systems in nature. Their structures were determined by NMR spectroscopic analysis, computer-assisted structure elucidation methods, quantum chemical calculations, and X-ray diffraction. A hypothetical biogenetic pathway begins with typical guaiane sesquiterpene (a), including a key intermediate (4) was proposed. Daphnenoids B and C (2 and 3) exhibited potential inhibitory activities on the production of NO against LPS-induced BV2 microglial cells.

Structural Revisions of Two Highly Aromatic Naphthoquinone-Derived Dimers Based on NMR Analysis, Computer-Assisted Structure Elucidation Methods, and Computations.

Eleucanainones A and B are two structurally complex naphthoquinone-derived dimers whose structure identification is difficult. Large yellow fragments of the preliminary CASE (computer-assisted structure elucidation) analysis revealed that the original structures might be questionable. Structural revisions of the two compounds were proposed on the basis of NMR analysis, CASE methods, conformation analysis, and DFT (density functional theory) NMR calculations with a custom DP4+ analysis. In addition, a polyketide-folded biosynthetic pathway of the two revised structures was proposed.

LC-HRMS-Database Screening Metrics for Rapid Prioritization of Samples to Accelerate the Discovery of Structurally New Natural Products.

In order to accelerate the isolation and characterization of structurally new or novel secondary metabolites, it is crucial to develop efficient strategies that prioritize samples with greatest promise early in the workflow so that resources can be utilized in a more efficient and cost-effective manner. We have developed a metrics-based prioritization approach using exact LC-HRMS, which uses data for 24 618 marine natural products held in the PharmaSea database. Each sample was evaluated and allocated a metric score by a software algorithm based on the ratio of new masses over the total (sample novelty), ratio of known masses over the total (chemical novelty), number of peaks above a defined peak area threshold (sample complexity), and peak area (sample diversity). Samples were then ranked and prioritized based on these metric scores. To validate the approach, eight marine sponges and six tunicate samples collected from the Fiji Islands were analyzed, metric scores calculated, and samples targeted for isolation and characterization of new compounds. Structures of new compounds were elucidated by spectroscopic techniques, including 1D and 2D NMR, MS, and MS/MS. Structures were confirmed by computer-assisted structure elucidation methods (CASE) using the ACD/Structure Elucidator Suite.

Structural Characterization of a Phenoxazine Analog Formed as a By-product of the Synthesis of a 3-Amino-N,N-dimethylsalicylamide

A highly colored impurity formed at low levels during the preparation of 3-amino N,N-dimethyl salicylamide was isolated and identified as 2-amino-N,N,N′,N′-tetramethyl-3-oxo-3H-phenoxazin-4,6-dicarboxamide using mass spectrometry and two-dimensional NMR methods that included long-range 1H-15N heteronuclear chemical shift correlation data to assemble the proton-deficient “right-half” of the 2-aminophenoxazin-3-one nucleus. The structure was independently confirmed using computer-assisted structure elucidation methods and by synthesis.

Elucidating ‘undecipherable’ chemical structures using computer‐assisted structure elucidation approaches

Structure elucidation using 2D NMR data and application of traditional methods of structure elucidation are known to fail for certain problems. In this work, it is shown that computer-assisted structure elucidation methods are capable of solving such problems. We conclude that it is now impossible to evaluate the capabilities of novel NMR experimental techniques in isolation from expert systems developed for processing fuzzy, incomplete and contradictory information obtained from 2D NMR spectra.

Long‐Range 1H—15N Heteronuclear Shift Correlation

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