Tedanolide and the evolution of polyketide inhibitors of eukaryotic protein synthesis

This Highlight covers the chemical and biological studies regarding a set of polyketide inhibitors of eukaryotic protein synthesis related to the marine-derived cytotoxic agent tedanolide.     

Two new betaines from the Australian bryozoan Amathia lamourouxi

A chemical investigation of the eastern Australian endemic bryozoan Amathia lamourouxi led to the isolation of two unique betaine molecules, lamouroic acid trifluoroacetate and lamourimidazolinium trifluoroacetate. The structures of these molecules were determined using (+)-HRESIMS, 2D NMR and ECD analyses. The new compounds were screened for antiplasmodial, cytotoxic and antibacterial activity but were inactive at 40 μM. Lamouroic acid trifluoroacetate is structurally related to the ubiquitous marine compound homarine, that has previously been shown to possess feeding deterrent properties, and this suggests that the new compound may also have an ecological role in the bryozoan.     

Syntheses of the tedanolides

This Highlight covers the synthetic contributions leading to the syntheses of tedanolide and 13-deoxytedanolide or the corresponding macrolactones, respectively. Additionally, the first SAR data for 13-deoxytedanolide (published by Fusetani) are presented.     

Some recent advances in the synthesis of polycyclic imidazole-containing marine natural products

This Highlight describes some of the recent synthetic work on imidazole-containing alkaloids isolated from marine sponges. Target molecules have been chosen which demonstrate synthetic strategies leading towards metabolites containing intact imidazole moieties as well as systems bearing modified imidazole rings.     

Beta-carboline alkaloids from a New Zealand marine bryozoan,Cribricellina cribraria

The crude extract of a New Zealand marine bryozoan Cribricellina cribraria was examined and resulted in the isolation of the previously described, 6-hydroxyharman (1) and the new beta-carboline metabolite, 8-hydroxyharman (2).     

Synthesis and biological evaluation of caulibugulones A-E

The marine bryozoan metabolites caulibugulone A-E were prepared from a readily available isoquinoline dione. These natural products were found to be potent and selective inhibitors of the dual specificity phosphatase Cdc25B.     

Surface functionalization of nanoparticles for nanomedicine

Control of interactions between nanoparticles and biosystems is essential for the effective utilization of these materials in biomedicine. A wide variety of nanoparticle surface structures have been developed for imaging, sensing, and delivery applications. In this research Highlight, we will emphasize advances in tailoring nanoparticle interfaces for implementation in nanomedicine.     

Carbolines. Part VII. Anisidines,convenient tools to synthesize hydroxy-β-carbolines

The paper describes a convenient synthesis of hydroxy-β-carbolines from commercial anisidines based on key steps such as metalation, cross-coupling and cyclization. The first total synthesis of a major cyto-toxic constituent of a marine bryozoan is also reported, the 8-hydroxy-1-vinyl-β-carboline.     

Direct C−H Bond Borylation of (Hetero)Arenes: Evolution from Noble Metal to Metal Free

Organoboron compounds are among the most versatile and useful building blocks in modern synthetic chemistry. The past decades have seen impressive developments in the direct C?H bond borylation of (hetero)arenes in which the applied catalysts are shifting from noble metals to metal‐free systems. This Highlight gives a brief summary on this evolution and focuses on recent elegant work in this field.     

Recent developments in enzymatic chlorination

While the existence of chlorinated natural products has been known for over 100 years, our understanding of the enzymology of biological chlorination reactions has been limited to chloroperoxidases, which are now known not to play a significant role in chlorometabolite biosynthesis. The discoveries of new classes of halogenases, described in this Highlight, have shed new light on the mechanisms of enzymatic chlorination of aromatic and aliphatic compounds.     

Recent developments in ambient ionization techniques for analytical mass spectrometry

Ambient ionization techniques enable the interrogation of a variety of samples in their native state by mass spectrometry, and are rapidly advancing all fields where screening for the presence of various analytes in a broadband and/or high-throughput fashion is desirable. This Highlight article provides an introduction to the field, and showcases the different ionization approaches reported since 2004, with an emphasis on the most recent developments.     

Chlorosulfolipids: structure, synthesis, and biological relevance

Chlorosulfolipids have been isolated from freshwater algae and from toxic mussels. They appear to have a structural role in algal membranes and have been implicated in Diarrhetic Shellfish Poisoning. Further fascinating aspects of these compounds include their stereochemically complex polychlorinated structures and the resulting strong conformational biases, and their poorly understood (yet surely compelling) biosynthesis. Discussions of each of these topics and of efforts in structural and stereochemical elucidation and synthesis are the subject of this Highlight.     

Nanomaterial-based electrochemical biosensors

The unique properties of nanoscale materials offer excellent prospects for interfacing biological recognition events with electronic signal transduction and for designing a new generation of bioelectronic devices exhibiting novel functions. In this Highlight I address recent research that has led to powerful nanomaterial-based electrical biosensing devices and examine future prospects and challenges. New nanoparticle-based signal amplification and coding strategies for bioaffinity assays are discussed, along with carbon-nanotube molecular wires for achieving efficient electrical communication with redox enzyme and nanowire-based label-free DNA sensors.     

New electrodes for old: from carbon nanotubes to edge plane pyrolytic graphite

Different types of carbon based electrodes have emerged over the last few years, significantly changing the scope and sensitivity of electro-analytical methods for the measurement of diverse targets from metal ions through gases to biological markers. This Highlight article shows how the use of carbon nanotube modified electrodes has led to a fundamental understanding of the location and nature of electron transfer processes on graphitic electrodes and to the realisation that edge plane pyrolytic graphite may represent, at present, an optimal electrode material of this type for electroanalysis.     

Synthesis of analogs of amathamide A and their preliminary antimicrobial activity

Syntheses of three non-brominated analogs of amathamide A (1), a natural alkaloid isolated from the Tasmanian marine bryozoan Amathia wilsoni, are described. Antimicrobial activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomona aeruginosa, and Candida albicans was tested. Test results for amathamide A (1) showed a weak activity against C. albicans and E. coli. The three non-natural analogs 2-4 proved to be inactive compounds.     

Isoprenoid-like alkylations in polyketide biosynthesis

Polyketides are secondary metabolites biosynthesized by the iterative Claisen condensation of malonate units. Despite utilizing only a small set of biochemical transformations, the polyketide biosynthetic machinery yields products of striking structural complexity and diversity. Recently, a new polyketide alkylation pathway was characterized that allows access to "beta-branched" structures. This Highlight will describe this alkylation sequence, with special emphasis on its parallels to isoprenoid biosynthesis from primary metabolism and the scope of structures accessible via this pathway.     

Myxobacterial natural product assembly lines: fascinating examples of curious biochemistry

Over the last 20 years myxobacteria have made their way from highly exotic organisms to one of the major sources of microbial natural products with interesting biological activities. Recent progress towards achieving a better understanding of the genetics and the biochemistry of myxobacterial secondary metabolism, revealed the involvement of numerous exceptional combinations of polyketide synthases and nonribosomal peptide synthetases operating far from textbook biosynthetic logic. In this Highlight, selected examples of recently described systems are discussed in comparison to all myxobacterial natural product assembly lines known to date.     

Synthesis of 8-desbromohinckdentine A1

Hinckdentine A is an alkaloid isolated from the bryozoan Hincksinoflustra denticulate. This natural product contains a novel and unique 11b,12,13,14,15,16-hexahydroazepino[4',5':2,3]indolo[1,2-c]quinazoline ring system that has not previously been synthesized. We have synthesized 8-desbromohinckdentine A from a 2-aryl indole by first preparing the quaternary center of the natural product and then building the seven-membered lactam and dihydropyrimidine rings onto this intermediate to form the framework of hinckdentine A.     

Wilsoniamines A and B: novel alkaloids from the temperate Australian bryozoan, Amathia wilsoni

Two novel alkaloids, wilsoniamines A and B, both possessing a hexahydropyrrolo[1,2-c]imidazol-1-one ring system that has not previously been found in nature, together with a new alkaloid, amathamide H and a known alkaloid, amathamide C were isolated from the temperate Australian bryozoan, Amathia wilsoni. MS and NMR analysis established the structure of the new compounds and indicated that the structure of amathamide C and several related compounds be revised. Amathamides C and H showed moderate anti-malarial and anti-trypanosomal activity.     

Total synthesis of flustramine C via dimethylallyl rearrangement

The marine natural product flustramine C from the bryozoan Flustra foliacea was synthesized in five steps and 38% yield starting from Nb-methyltryptamine. The key step is the biomimetic oxidation of the natural product deformylflustrabromine causing selective 1,2-rearrangement of the inverse prenyl group. By 1H,15N HMBC experiments, it is unambiguously shown that the reaction with t-BuOCl commences with chlorination of the side chain nitrogen. Deformylflustrabromine itself was synthesized via Danishefsky inverse prenylation. [reaction: see text].