Rising resistance to current clinical antibacterial agents is an imminent threat to global public health and highlights the demand for new lead compounds for drug discovery. One such potential lead compound, the peptide antibiotic teixobactin, was recently isolated from an uncultured bacterial source, and demonstrates remarkably high potency against a wide range of resistant pathogens without apparent development of resistance. A rare amino acid residue component of teixobactin, enduracididine, is only known to occur in a small number of natural products that also possess promising antibiotic activity. This review highlights the presence of enduracididine in natural products, its biosynthesis together with a review of analogues of enduracididine. Reported synthetic approaches to the cyclic guanidine structure of enduracididine are discussed, illustrating the challenges encountered to date in the development of efficient synthetic routes to facilitate drug discovery efforts inspired by the discovery of teixobactin.

The rubromycins are an ever growing family of natural products isolated from various Actinomycetes over the last 60 years. Exhibiting a highly attractive array of antimicrobial and enzyme activity, this unique family of compounds have attracted significant attention from many synthetic chemists. Investigations into the synthesis of the densely functionalised hexacyclic ring system have revealed many hidden synthetic challenges. This review covers the isolation, the reported biological activity and the detailed synthetic studies towards these complex natural products.

A full account of the evolution of a convergent total synthesis of gonytolide C is reported. The assembly of the natural product core relies on a Horner-Wadsworth-Emmons (HWE) olefination followed by an intramolecular oxa-Michael addition. Robust and efficient preparations of both HWE coupling part-

Twenty nine novel spiroketal derivatives related to the rubromycins were evaluated for their anti-telomerase activity using the real-time quantitative telomeric repeat amplification protocol assay. The parent compound g-rubromycin exhibited the highest potency against human telomerase activity within the series. Modification of the spiroketal motif by the introduction of heteroatoms and substituents at different positions produced analogues with varying bioactivity. Variation at the isocoumarin subunit of the title compound resulted in weaker activity, indicative of its importance in telomerase inhibition.