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In recent years, the chemical potential of bismuth and bismuth compounds has been actively exploited. Bismuth salts are known for their low toxicity, making them potential valuable reagents for large-scale synthesis, which becomes more obvious when dealing with products such as active pharmaceutical ingredients or synthetic intermediates. Conversely, bismuth compounds have been widely used in medicine. After extensive use in the treatments of syphilis and other bacterial infections before the advent of modern antibiotics, bismuth compounds remain important for the treatment of several gastrointestinal disorders and also exhibit antimicrobial properties and cytotoxic activity, among others. This review updates relevant advances in the past few years, concerning the application of bismuth reagents and catalysts in innovative synthetic processes for the preparation of compounds of medicinal interest, as well as the preparation, biological evaluation and potential medicinal uses of bismuth compounds.

In recent years,extensive sequencing and annotation of bacterial genomes has revealed an unexpectedly large number of secondary metabolite biosynthetic gene clusters whose products are yet to be discovered. Fore xample, cyanobacterial genomes contain avariety of gene clusters that likely incorporate fatty acid derived moieties,b ut for most cases we lack the knowledge and tools to effectively predict or detect the encoded natural products.H ere,w ee xploit the apparent absence of af unctional b-oxidation pathway in cyanobacteria to achieve efficient stable-isotope-labeling of their fatty acid derived lipidome.W es how that supplementation of cyanobacterial cultures with deuterated fatty acids can be used to easily detect natural product signatures in individual strains.T he utility of this strategy is demonstrated in two cultured cyanobacteria by uncovering analogues of the multidrug-resistance reverting hapalosin, and novel, cytotoxic, lactylate-nocuolin Ah ybrids-the nocuolactylates.

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Esterification reactions are central to many aspects of industrial and biological chemistry. The formation of carboxyesters typically occurs through nucleophilic attack of an alcohol onto the carboxylate carbon. Under certain conditions employed in organic synthesis, the carboxylate nucleophile can be alkylated to generate esters from alkyl halides, but this reaction has only been observed transiently in enzymatic chemistry. Here, we report a carboxylate alkylating enzyme-BrtBthat catalyzes O-C bond formation between free fatty acids of varying chain length and the secondary alkyl halide moieties found in the bartolosides. Guided by this reactivity, we uncovered a variety of natural fatty acid-bartoloside esters, previously unrecognized products of the bartoloside biosynthetic gene cluster.

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Natural products have an important role in several human activities, most notably as sources of new drugs. In recent years, massive sequencing and annotation of bacterial genomes has revealed an unexpectedly large number of secondary metabolite biosynthetic gene clusters whose products are yet to be discovered. For example, cyanobacterial genomes contain a large number of gene clusters that likely incorporate fatty acid-derived moieties, but for most cases we lack the knowledge and tools to effectively predict or detect the encoded natural products. Here, we exploit the apparent lack of a functional beta-oxidation pathway in cyanobacteria to achieve efficient stable-isotope labeling of their fatty acid-derived lipidome. We show that supplementation of cyanobacterial cultures with deuterated fatty acids can be used to easily detect natural product signatures in individual strains. The utility of this strategy is demonstrated in two cultured cyanobacteria by uncovering analogues of the multidrug-resistance reverting hapalosin, and novel, cytotoxic, lactylate-nocuolin A hybrids – the nocuolactylates.

No abstract