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Isoprene units derived from dimethylallyl diphosphate (DMAPP) are an important motif in many natural products including terpenoids, carotenoids, steroids, and natural rubber. Understanding the chemical characteristics of DMAPP is an important topic in natural products chemistry, organic chemistry, and biochemistry. We have developed a direct bioinspired indole prenylation reaction using DMAPP or its equivalents as the electrophile in homogeneous aqueous acidic media in the absence of enzyme to provide prenylated indole products. After establishing the bioinspired indole prenylation reaction, this was then used to achieve the synthesis of a series of natural products, namely, N-prenylcyclo-l-tryptophyl-l-proline, tryprostatins, rhinocladins, and terezine D.

Fungi are morphologically, ecologically, metabolically, and phylogenetically diverse. They are known to produce numerous bioactive molecules, which makes them very useful for natural products researchers in their pursuit of discovering new chemical diversity with agricultural, industrial, and pharmaceutical applications. Despite their importance in natural products chemistry, identification of fungi remains a daunting task for chemists, especially those who do not work with a trained mycologist. The purpose of this review is to update natural products researchers about the tools available for molecular identification of fungi. In particular, we discuss (1) problems of using morphology alone in the identification of fungi to the species level; (2) the three nuclear ribosomal genes most commonly used in fungal identification and the potential advantages and limitations of the ITS region, which is the official DNA barcoding marker for species-level identification of fungi; (3) how to use NCBI-BLAST search for DNA barcoding, with a cautionary note regarding its limitations; (4) the numerous curated molecular databases containing fungal sequences; (5) the various protein-coding genes used to augment or supplant ITS in species-level identification of certain fungal groups; and (6) methods used in the construction of phylogenetic trees from DNA sequences to facilitate fungal species identification. We recommend that, whenever possible, both morphology and molecular data be used for fungal identification. Our goal is that this review will provide a set of standardized procedures for the molecular identification of fungi that can be utilized by the natural products research community.

High-throughput natural products chemistry methods have facilitated the isolation of eight new and two known beilschmiedic acid derivatives from the leaves of a Gabonese species of Beilschmiedia. This class of compounds appears to be unique to two genera of the Lauraceae, and exhibits remarkable structural complexity for a fatty acid. Eight of the compounds were isolated in microgram quantities necessitating the use of a 1.7mm MicroCryoProbe to obtain NMR data, including a complete HMBC, for structure elucidation and dereplication. All of the compounds were screened for cytotoxic activity against NCI-H460 human lung cancer cells and antibacterial activity against a clinical isolate of methicillin-resistant Staphylococcus aureus. Results from enzymatic assays provided evidence that the observed activity was not the result of membrane disruption as one might expect from lipophilic compounds such as these.

An assessment of the technology and method development in countercurrent chromatography (CCC) and centrifugal partition chromatography (CPC), collectively referred to as countercurrent separation (CS), is provided. More than six decades of CS theory and applications are critically reviewed and developed into a practical guide to CS for natural products research. The necessary theoretical foundation is given for better use of CS in the separation of biological molecules of any size, small to large, and from any matrix, simple to complex. The three operational fundamentals of CS--instrumentation, biphasic solvent systems, and theory--are covered in a prismatic fashion. The goal of this review is to provide the necessary background and references for an up-to-date perspective of CS and to point out its potential for the natural products scientist for applications in natural products chemistry, metabolome, and proteome research involving organisms from terrestrial and marine sources.

Chemical investigation of a MeOH extract of the Great Barrier Reef ascidian Didemnum albopunctatum has led to the isolation and identification of a new anthrone-anthraquinone, albopunctatone (1), together with the known 1,8-dihydroxy-9,10-anthraquinone (2). The structure of 1 was established from interpretation of 1D and 2D NMR spectroscopic and mass spectrometric data. The compounds were screened for antiplasmodial activity against chloroquine-resistant and -sensitive strains of the malaria parasite, Plasmodium falciparum. Albopunctatone (1) was moderately active against both strains (IC(50) 5.3 and 4.4 ± 0.5 μM, respectively), while 2 was inactive at doses up to 40 μM. Both compounds were also inactive up to 40 μM when tested against a variety of cancerous and normal human cell lines and the kinetoplastid Trypanosoma brucei brucei, indicating selectivity for the malaria parasite, P. falciparum.

High-throughput natural products chemistry methods have led to the isolation of three new (1-3) and two known indole sesquiterpene alkaloids (4, 5) from Greenwayodendron suaveolens. Their structures were determined using CapNMR and MS. Pentacyclindole (1) was determined to possess a new natural product framework. Pentacyclindole (1) and polyalthenol (4) showed activity against clinical isolates of Staphylococcus aureus with polyalthenol (4) demonstrating a MIC(90) of 4 microg/mL.

A Papua New Guinea field collection of the marine cyanobacterium Blennothrix cantharidosmum was investigated for its cytotoxic constituents. Bioassay-guided isolation defined the cytotoxic components as the known compounds lyngbyastatins 1 and 3. However, six new acyl proline derivatives, tumonoic acids D-I, plus the known tumonoic acid A were also isolated. Their planar structures were defined from NMR and MS data, while their stereostructures followed from a series of chiral chromatographies, degradation sequences, and synthetic approaches. The new compounds were tested in an array of assays, but showed only modest antimalarial and inhibition of quorum sensing activities. Nevertheless, these are the first natural products to be reported from this genus, and this inspired a detailed morphologic and 16S rDNA-based phylogenetic analysis of the producing organism.

Brazil is blessed with a great biodiversity, which constitutes one of the most important sources of biologically active compounds, even if it has been largely underexplored. As is the case of the Amazon and Atlantic rainforests, the Brazilian marine fauna remains practically unexplored in the search for new biologically active natural products. Considering that marine organisms have been shown to be one of the most promising sources of new bioactive compounds for the treatment of different human diseases, the 8000 km of the Brazilian coastline represents a great potential for finding new pharmacologically active secondary metabolites. This review presents the status of marine natural products chemistry in Brazil, including results reported by different research groups with emphasis on the isolation, structure elucidation, and evaluation of biological activities of natural products isolated from sponges, ascidians, octocorals, and Opistobranch mollusks. A brief overview of the first Brazilian program on the isolation of marine bacteria and fungi, directed toward the production of biologically active compounds, is also discussed. The current multidisciplinary collaborative program under development at the Universidade de Sao Paulo proposes to establish a new paradigm toward the management of the Brazilian marine biodiversity, integrating research on the species diversity, ecology, taxonomy, and biogeography of marine invertebrates and microorganisms. This program also includes a broad screening program of Brazilian marine bioresources, to search for active compounds that may be of interest for the development of new drug leads.