CARBOHYDRATE CHEMISTRY O O Through the Looking Glass O * * * Angew

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NATURAL PRODUCTS obtain information that would otherwise be Crowdsourcing drug discovery inaccessible, whilst also engaging the public Angew. Chem. Int. Ed. http://doi.org/ in the scientific process. RJ f2nz62 (2013) CARBOHYDRATE CHEMISTRY O O Through the looking glass O * * * Angew. Chem. Int. Ed. http://doi.org/ O f2n5mn (2013) N Creative chemistry Naturally occurring sugars are a readily Bloggers combine chemistry and the arts HO OH OH available, cheap source of chirality and have for striking results. frequently been used as the starting point © 2013 WILEY OH for stereoselective syntheses. They are often, ‘Creative’ may not be the first adjective that however, only easily available in one mirror- comes to mind when describing chemists. Fungal natural products include a diverse image form, with their respective enantiomers Despite comparisons one might make range of chemical structures and often being scarce and expensive. Moreover, the between chemical synthesis and the ‘dark possess interesting biological properties — unnatural isomers may be endowed with arts’, the stereotype of a chemist is that of a such as anticancer or antimicrobial activity. interesting and potentially useful biological methodical, analytical thinker rather than a However, it is difficult to collect and isolate a properties. Now, Sarah Jenkinson and creative and artistic one. Several chemistry large range of fungal species to analyse, and co-workers from the University of Oxford, bloggers are helping to dispel this myth, so far only a small percentage of metabolites alongside colleagues from Kagawa University, however, by sharing their science in the from fungal species has been tested for have reported a rapid and easily scalable form of photographs, digital art or poetry. bioactivity. Taking a collaborative approach conversion of natural d-glucose to either Kristof Hegedüs blogs at Pictures to this problem, a team led by Susan l-glucose or l-glucoronic acid. from an Organic Chemistry Laboratory, Mooberry and Robert Cichewicz from the d-Glucose has a six-carbon chain and where each day he shares a photograph of University of Texas Health Science Center four stereocentres, but Jenkinson and something from his lab. Subjects range from and the University of Oklahoma respectively, co-workers planned a synthetic conversion crystals (http://go.nature.com/CxM6IS), enlisted the help of ‘citizen scientists’ to to the enantiomer by forming a new carbon– to experimental set-ups (http://go.nature. collect soil samples from different regions. carbon bond at one end of the chain, and com/28sdhR) and interesting reagents Crowdsourcing sample collection enabled breaking one at the other. The first step in the (http://go.nature.com/GsSeaR). Each them to isolate and analyse metabolites from sequence is a Felkin–Anh Kiliani ascension post is accompanied by a short description a greater range of fungal species. — a reaction known since the 1930s — in to explain what is shown in the picture. This approach led to the discovery of a which cyanide is diastereoselectively added Nevertheless, the focus is primarily on the previously unknown natural product, which to the aldehyde before hydrolysis of the photography, with the simple aesthetics of the team called maximiscin. They found nitrile to produce a seven-carbon sodium laboratory glassware a recurring theme. that by altering the culture medium for a carboxylate. Reduction of the carboxylate A recent post (http://go.nature.com/ strain of crowdsourced Tolypocladium, or would lead to a meso-intermediate, but QDORoS) from the Picture it… Chemistry by co-culturing the strain with a species of Jenkinson and co-workers avoid this with a blog featured the opium poppy Papaver bacteria, they could switch on an otherwise short and highly effective protecting group somniferum, popularly known for its silent biosynthetic pathway that led to sequence. In one step, the six hydroxy groups psychoactive alkaloids. The blog post this natural product. The team probed (three diols) are protected as a triacetonide begins on a surreal note, with a picture of a the biosynthetic origins of maximiscin by group and the carboxylate is converted to an poppy growing out of an Allihn condenser including isotope-labelled precursors in ester. Only one of three possible triacetonide used to demonstrate a laboratory extraction the culture medium and identifying where isomers is formed, and then one acetonide of opioids. The post concludes with they were incorporated into the structure. is unmasked in preparation for the key discussion of total syntheses of morphine These labelling experiments revealed that carbon–carbon cleavage reaction. Reduction and codeine, incorporating some classics of maximiscin consists of two moieties that of the ester, oxidative cleavage of the diol and synthetic chemistry such as the Diels–Alder are synthesized by different biosynthetic global deprotection leads to l-glucose. A reaction and reductive amination. pathways. One moiety is produced via the small change to the sequence, with oxidative Finally, to transition from pictures known ‘shikimate pathway’, and the other via cleavage of the diol first, before an unmasking back to words, Mark Lorch at Chemistry a route that includes a polyketide synthase of the hydroxy groups and cleavage of the Blog recently hosted a number of limerick and a non-ribosomal peptide synthetase. ester leads to l-glucoronic acid. poems written by Nicholas Dawson. These two moieties are linked by an unusual The l-enantiomer of glucose is known With topics ranging from Viagra (http:// O=C–N–O–C bridge. to be almost as sweet as its natural go.nature.com/6CEGOM) to the Maximiscin was shown to possess counterpart, but has no calorific value. vulcanization of rubber (http://go.nature. useful anticancer properties. Screening Some nasty side-effects, however, will com/46taoR) to phlogiston theory tests revealed that the natural product prevent use in food, but this synthesis will (http://go.nature.com/UBt6bc), it was a inhibited the growth of several cancer cell provide a useful starting point for that of refreshing and whimsical way to rediscover lines. Follow-up studies using a mouse other l-sugars and investigations of their some of the milestones of chemical history. model of cancer demonstrated that it can biological properties. SD also significantly inhibit tumour growth Written by Renée Webster, who blogs at in mice. The team say that crowdsourcing Written by Stuart Cantrill, Stephen Davey, www.lostinscientia.wordpress.com approaches can enable research teams to Russell Johnson and Paul MacLellan.

NATURE CHEMISTRY | VOL 6 | FEBRUARY 2014 | www.nature.com/naturechemistry 87