Electrophilic natural products and their biological targets

The study of biologically active natural products has resulted in seminal contributions to our understanding of living systems. In the case of electrophilic natural products, the covalent nature of their interaction has largely facilitated the identification of their biological binding partners. In this review, we provide a comprehensive compilation of electrophilic natural products from all major chemical classes together with their biological targets. Covering Michael acceptor systems, ring-strained compounds and other electrophiles, such as esters or carbamates, we highlight representative and instructive examples for over 20 electrophilic moieties. The fruitful cooperation of natural product chemistry, medicinal chemistry and chemical biology has produced a collection of well-studied examples for how electrophilic natural products exert their biological functions that range from antibiotic to antitumor effects. Special emphasis is put on the elucidation of their respective biological targets via activity-based protein profiling, which together with the recent advancements in mass spectrometry has been crucial to the success of the field. The wealth of naturally occurring electrophilic moieties and their chemical complexity enables binding of a large variety of biological targets, such as enzymes of all classes, nonenzymatic proteins, DNA and other cellular compounds. With approximately 30,000 genes in the human genome but only 266 confirmed protein drug targets, the study of biologically active, electrophilic natural products has the potential to provide insights into fundamental biological processes and to greatly aid the discovery of new drug targets.     

Sweet and umami taste: natural products, their chemosensory targets, and beyond

Much of our appreciation of food is due to the excitement of the perception of "sweet" and "umami" taste. With a special focus on natural products, this Review gives a summary of compounds that elicit and modulate "sweet" or "umami" taste responses. It will be discussed how the interaction of these molecules with the oral sweet and umami taste receptors stimulates receptor cells to secrete neurotransmitters to induce neural activity that is conveyed to the cerebral cortex to represent sweet and umami taste, respectively. Recent data also show that a sweet taste is metabolically relevant for fuel homeostasis and linked to appetitive ingestive behavior.     

A natural love of natural products

Recent research on the chemistry of natural products from the author's group that led to the receipt of the ACS Ernest Guenther Award in the Chemistry of Natural Products is reviewed. REDOR NMR and synthetic studies established the T-taxol conformation as the bioactive tubulin-binding conformation, and these results were confirmed by the synthesis of compounds which clearly owed their activity or lack of activity to whether or not they could adopt the T-taxol conformation. Similar studies with the epothilones suggest that the current tubulin-binding model needs to be modified. Examples of natural products discovery and biodiversity conservation in Suriname and Madagascar are also presented, and it is concluded that natural products chemistry will continue to make significant contributions to drug discovery.     

Antimycobacterial natural products

This review covers the literature published between January 1990 and December 2002 (inclusive) for natural products with reported antimycobacterial activity, with 248 citations to 352 compounds isolated from both terrestrial and marine sources The compounds are presented in order of chemical type, namely lipids/fatty acids and simple aromatics phenolics and acetogenic quinones, peptides, alkaloids, terpenes (monoterpenoids, diterpenes, sesquiterpenes, sesterterpenes and triterpenes) and steroids.     

Marine natural products

Covering: 2010. Previous review: Nat. Prod. Rep., 2011, 28, 196. This review covers the literature published in 2010 for marine natural products, with 895 citations (590 for the period January to December 2010) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1003 for 2010), together with the relevant biological activities, source organisms and country of origin. Biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included.     

Marine natural products

This review covers the literature published in 2002 for marine natural products, with 579 citations (413 for the period January to December 2002) referring to compounds isolated from marine microorganisms and phytoplankton, green algae, brown algae, red algae, sponges, coelenterates, bryozoans, molluscs, tunicates and echinoderms. The emphasis is on new compounds (677 for 2002), together with their relevant biological activities, source organisms and country of origin. Syntheses that lead to the revision of structures or stereochemistries have been included (114), including any first total syntheses of a marine natural product.     

Fluorine-containing natural products

It is now more than 50 years since the first fluorinated natural product was identified. In that time only about a dozen fluorinated natural products have been isolated, the last one over a decade ago. Very little is known about the mechanism of biological fluorination although significant progress has been made in elucidating the pathway by which biosynthesis of fluoroacetate and 4-fluorothreonine occurs in the bacterium Streptomyces cattleya. In this article we review the fluorinated natural products and the current status of our understanding of fluorometabolite biosynthesis.     

Marine natural products

This review covers the literature published in 2001 for marine natural products, with 497 citations (373 for the period January to December 2001) and includes 793 compounds isolated from marine microorganisms and phytoplankton, green algae, brown algae, red algae, sponges, coelenterates, bryozoans, molluscs, tunicates and echinoderms. The emphasis is on new compounds and new stereochemical assignments (683 for 2001), together with relevant biological activities, source organisms and country of origin. Syntheses that confirm or revise structures or stereochemistries have been included (95), including any first total synthesis of a marine natural product.     

Marine natural products

This review covers the literature published in 2004 for marine natural products, with 693 citations (491 for the period January to December 2004) referring to compounds isolated from marine microorganisms and phytoplankton, green algae, brown algae, red algae, sponges, coelenterates, bryozoans, molluscs, tunicates and echinoderms. The emphasis is on new compounds (716 for 2004), together with their relevant biological activities, source organisms and country of origin. Biosynthetic studies (8), and syntheses (80), including those that lead to the revision of structures or stereochemistries, have been included.     

Marine natural products

This review covers the literature published in 2005 for marine natural products, with 704 citations (493 for the period January to December 2005) referring to compounds isolated from marine microorganisms and phytoplankton, green algae, brown algae, red algae, sponges, coelenterates, bryozoans, molluscs, tunicates and echinoderms. The emphasis is on new compounds (812 for 2005), together with their relevant biological activities, source organisms and country of origin. Biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included.     

Marine natural products

This review covers the marine natural products literature for the year 2000 and is organized phylogenetically, with sections on marine microorganisms and phytoplankton, green algae, brown algae, red algae, sponges, coelenterates, bryozoans, molluscs, tunicates. echinoderms and miscellaneous marine organisms. There is an emphasis on new structures, stressing their biological activities, source organisms and countries of origin, and also syntheses that confirm the structures of known compounds. The review contains 869 structures and 592 references, of which 434 appeared between January and December 2000.     

Marine natural products

This review covers the literature published in 2003 for marine natural products, with 619 citations (413 for the period January to December 2003) referring to compounds isolated from marine microorganisms and phytoplankton, green algae, brown algae, red algae, sponges, coelenterates, bryozoans, molluscs, tunicates and echinoderms. The emphasis is on new compounds (656 for 2003), together with their relevant biological activities, source organisms and country or origin. Biosynthetic studies or syntheses that lead to the revision of structures or stereochemistries have been included (78), including any first total syntheses of a marine natural product.     

Marine natural products

This review covers the literature published in 2006 for marine natural products, with 758 citations (534 for the period January to December 2006) referring to compounds isolated from marine microorganisms and phytoplankton, green algae, brown algae, red algae, sponges, cnidaria, bryozoans, molluscs, tunicates and echinoderms. The emphasis is on new compounds (779 for 2006), together with their relevant biological activities, source organisms and country of origin. Biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included.