Towards colombiasin A

A synthetic route to an unnatural diastereoisomer of colombiasin A is described. Key features are an arene alkylation with a gamma -methylene-gamma -butyrolactone and an intramolecular Diels-Alder cycloaddition

Intramolecular radical cyclisations to pyridines

Intramolecular radical additions to the alpha-, beta- and gamma -carbons of a pyridine have each been shown to be facile processes. When a cis-alkene conjoins an ortho-iodoarene and a pyridine. radical cyclisation induced by homolysis of the carbon to iodine bond favours a 6-exo, endo-trig course. With a two carbon alkane conjoining the ortho-iodoarene and the pyridine, intermolecular hydrogen atom abstraction. 6-exo/endo-trig cyclisation and 5-exo-trig cyclisation modes compete. That the spirocyclic intermediates formed in the 5-exo-trig cyclisation rearrange with migration of the alkyl chain is noteworthy

The synthesis of a combretastatin A-4 based library and discovery of new cooperative ortho-effects in Wittig reactions leading to (Z)-stilbenes

A synthesis of combretastatin A-4 and a small library of analogues led to the discovery of some new cooperative ortho-­effects allowing (Z)-stilbenes to be prepared in high yield and dia­stereomeric ratio.<br/

Potassium carbonate-silica: a highly effective stationary phase for the chromatographic removal of organotin impurities

Organotin impurities in product mixtures can be reduced from stoichiometric levels to similar to 15 parts per million by column chromatography using 10% w/w anhydrous potassium carbonate-silica as a stationary phase

Triggering apoptosis in cancer cells with an analogue of cribrostatin 6 that elevates intracellular ROS

Elevation of reactive oxygen species (ROS) is both a consequence and driver of the upregulated metabolism and proliferation of transformed cells. The resulting increase in oxidative stress is postulated to saturate the cellular antioxidant machinery{,} leaving cancer cells susceptible to agents that further elevate their intracellular oxidative stress. Several small molecules, including the marine natural product cribrostatin 6, have been demonstrated to trigger apoptosis in cancer cells by increasing intracellular ROS. Here, we report the modular synthesis of a series of cribrostatin 6 derivatives, and assessment of their activity in a number of cell lines. We establish that placing a phenyl ring on carbon 8 of cribrostatin 6 leads to increased potency, and observe a window of selectivity towards cancer cells. The mechanism of activity of this more potent analogue is assessed and demonstrated to induce apoptosis in cancer cells by increasing ROS. Our results demonstrate the potential for targeting tumors with molecules that enhance intracellular oxidative stress

19th international isotope society (UK group) symposium: synthesis &amp; applications of labelled compounds 2010

The 19th annual symposium of the International Isotope Society’s United Kingdom Group took place at the Wellcome Genome Campus, Hinxton, Cambridge, UK on Thursday 14th October 2010. The meeting was attended by around 80 delegates from academia and industry, the life sciences, chemical, radiochemical and scientific instrument suppliers.The Harrowven contribution:Since Kekule ? first proposed his ouroboros-inspired structure for benzene in the mid-nineteenth century, it has been regarded as the archetypal aromatic compound – flat, with carbon-carbon bonds of equal length and bond angle.1 The viability of non-planar benzene rings has been known for many decades, with the first reported example of a boat-configured arene dating to the synthesis of [2.2]paracyclophane in 1949.2 However, it was arguably the isolation of (1)-cavicularin in 1996, and latterly of the haouamines and hirsutellones, that alerted the wider scientific community to the existence of biosynthetic pathways for the generation of such motifs in Nature (Figure 1).Through a combination of chemical synthesis (cavicularin,3,4 riccardin C3,4 and RP-664534), molecular modelling and data mining, we have strong evidence to suggest that boat-configured arenes are far more common in natural products than has been traditionally thought, spanning many classes including macrocyclic alkaloids, guaianolides, bisbibenzyls, peptides and biarylheptanoids. In addition, our work provides guidance for addressing the chemical synthesis of such targets