11B and 1H-11B HMBC NMR as a Tool for Identification of a Boron-Containing Nucleoside Dimer.

Boron-containing compounds are commonly used in synthetic chemistry and are known to play important roles in biology. Despite the widespread relevance of boronated compounds, there have been limited methods to discover, characterize, and study them. Here, we describe the use of 11B NMR, including 1H-11B HMBC, for the isolation and characterization of the boron-containing natural product diadenosine borate. Utilizing synthetic standards, we optimized coupling parameters for 1H-11B HMBC experiments to allow for the analysis of small quantities (∼1 mg) of boron-containing compounds. This work can facilitate the broader application of 11B NMR to the study of boron in a range of applications, from synthetic chemistry to the role of boron in naturally occurring systems.

Assembly of Terpenoid Cores by a Simple, Tunable Strategy.

Oxygenated, polycyclic terpenoid natural products have important biological activities. Although total synthesis of such terpenes is widely studied, synthetic strategies that allow for controlled placement of oxygen atoms and other functionality remains a challenge. Herein, we present a simple, scalable, and tunable synthetic strategy to assemble terpenoid-like polycycloalkanes from cycloalkanones, malononitrile, and allylic electrophiles, abundantly available reagent classes.

Boron NMR as a Method to Screen Natural Product Libraries for B-Containing Compounds.

Natural products are biologically relevant metabolites exploited for biomedicine and biotechnology. The frequent reisolation of known natural products questions whether existing discovery models are still capable of identifying novel compounds. As innovative NMR-based screening techniques can help overcome these challenges, we applied a phase cycling composite pulse sequence to 11B NMR experiments to enhance their sensitivity to screen libraries for novel boron-containing molecules. Aplasmomycin and autoinducer-2 were detected in crude and enhanced microbial fractions, via their boron signals, as proof of concept. Subsequently, a screen of 21 crude plant and 50 crude marine microbial extracts were chosen at random and analyzed with the optimized 11B experiment for feasibility as a high throughput discovery method. Eight of the plant samples and 13 of the microbial samples were identified as boron-containing, suggesting that there is a higher presence of boron metabolites available from natural sources than previously known due to a lack of appropriate discovery methods. As a result, we believe that this optimized 11B NMR experiment can serve as a robust method for quick and facile discovery of novel boron-containing metabolites from a variety of natural sources.

The Natural Products Atlas: An Open Access Knowledge Base for Microbial Natural Products Discovery.

Despite rapid evolution in the area of microbial natural products chemistry, there is currently no open access database containing all microbially produced natural product structures. Lack of availability of these data is preventing the implementation of new technologies in natural products science. Specifically, development of new computational strategies for compound characterization and identification are being hampered by the lack of a comprehensive database of known compounds against which to compare experimental data. The creation of an open access, community-maintained database of microbial natural product structures would enable the development of new technologies in natural products discovery and improve the interoperability of existing natural products data resources. However, these data are spread unevenly throughout the historical scientific literature, including both journal articles and international patents. These documents have no standard format, are often not digitized as machine readable text, and are not publicly available. Further, none of these documents have associated structure files (e.g., MOL, InChI, or SMILES), instead containing images of structures. This makes extraction and formatting of relevant natural products data a formidable challenge. Using a combination of manual curation and automated data mining approaches we have created a database of microbial natural products (The Natural Products Atlas, www.npatlas.org) that includes 24 594 compounds and contains referenced data for structure, compound names, source organisms, isolation references, total syntheses, and instances of structural reassignment. This database is accompanied by an interactive web portal that permits searching by structure, substructure, and physical properties. The Web site also provides mechanisms for visualizing natural products chemical space and dashboards for displaying author and discovery timeline data. These interactive tools offer a powerful knowledge base for natural products discovery with a central interface for structure and property-based searching and presents new viewpoints on structural diversity in natural products. The Natural Products Atlas has been developed under FAIR principles (Findable, Accessible, Interoperable, and Reusable) and is integrated with other emerging natural product databases, including the Minimum Information About a Biosynthetic Gene Cluster (MIBiG) repository, and the Global Natural Products Social Molecular Networking (GNPS) platform. It is designed as a community-supported resource to provide a central repository for known natural product structures from microorganisms and is the first comprehensive, open access resource of this type. It is expected that the Natural Products Atlas will enable the development of new natural products discovery modalities and accelerate the process of structural characterization for complex natural products libraries.

Design, synthesis and antimicrobial evaluation of novel benzoxazole derivatives.

The synthesis of (S)-2-(4-tert-butylphenoxy)-3-(benzoxazol-5-yl) propanoic acid derivatives (2a-k) were described and their in vitro antibacterial activities were determined against Gram-negative and -positive bacteria. These compounds were found to exert a broad spectrum of activity against the screened bacteria, but poor MIC values were found for Candida albicans fungi. Compound 2b bearing a hydrophobic aromatic tie was the most active derivative against all bacteria studied with MIC values ranging from 0.098 to 0.78 µg/mL. The activity of 2b against B. subtilis was 2-fold higher than Penicillin, and 8- to 510-fold higher than other control antibiotics.