research highlights

INTERLOCKED containing up to 16 acetylenic units, team of researchers led by Harry Anderson Protecting polyynes but these reactive species would readily at the University of Oxford and Rik Chem. Commun. 48, 7562–7564 (2012) polymerize if not kept in dilute solutions. Tykwinski at the University of Erlangen- Org. Lett. 14, 3424–3426 (2012) More recently, it has been found that placing Nuremberg, were able to make a series of bulky groups at each end of the carbon polyyne rotaxanes comprising 4, 6 or 10 chain results in stable compounds that can acetylenic units. In this case, however, the be isolated. polyyne chains were capped with ‘super-

© 2012 RSC The calming influence of the end trityl’ groups rather than metal-based groups on the reactivity of polyyne chains complexes. Anderson, Tykwinski and only extends so far, however, and as the co-workers then went on to demonstrate chains get longer, alternative approaches that the environment around the polyyne to modulate their behaviour are going chain could be influenced by binding a to be required. Now, two research teams metal ion to the phenanthroline group of have independently shown how polyyne the macrocycle. SC chains can be ‘insulated’ by encircling them with a macrocycle to produce DNA REPLICATION interlocked molecules known as rotaxanes. High fidelity Polyynes are compounds in which linear John Gladysz and co-workers from Texas J. Am. Chem. Soc. http://doi.org/h24 (2012) chains of sp-hybridized carbon atoms are A&M University coupled together pairs held together with alternating single and of butadiyne building blocks — each with DNA provides the blueprint for , therefore triple bonds. Not only have the somewhat a bulky -based group at one the importance of its accurate replication unusual composition and structure of these end — in the presence of a 33-membered cannot be underestimated. This is the job carbon-rich materials attracted the interest macrocyclic ring to give a tetrayne-based of DNA polymerases, a family of enzymes of chemists for many years, but they also rotaxane. In a process that is referred to as that take template strands of DNA and represent discrete examples of the proposed ‘active templating’, a ion bound to co-ordinate the creation of complementary one-dimensional allotrope of carbon known the macrocycle mediates the coupling of the strands, making sure that the correct as carbyne. two terminal . nucleotide is incorporated at each step. The As long ago as the 1970s, synthetic Using the same macrocycle and a similar breathtaking accuracy of the process (1 error chemists were able to make polyynes copper-mediated coupling approach, a for every 105-108 nucleotides added) is reliant

NATURAL PRODUCTS

Sensitive synthesis Angew. Chem. Int. Ed. 51, 6929–6933 (2012) Three of the most common justifications O O for total-synthesis campaigns are OAc (i) as tests for newly developed synthetic OtBu methodology, (ii) the interesting biological H activity of the natural products and O O (iii) the presence of synthetically O OH challenging or unusual carbon skeletons O in the structure. A rare example now reported by Alois Fürstner and co-workers from the Max-Planck-Institut für Kohlenforschung in Mülheim, Germany includes elements of all three. exists as a mixture of two diastereomers multiple bonds. Furthermore, the Neurymenolide A was first isolated that interconvert on a timescale of electrophilic catalyst must react fastest at from a species of red algae found in the several hours. the least electron-rich . South Pacific. It exhibits activity against The key feature of any synthesis of this Following formation of the desired both methicillin- and vancomycin- target is that the skipped polyene array pyrone, the macrocycle was formed using resistant bacteria — so the structure could (red) is likely to isomerize easily to the a molybdenum alkyne metathesis catalyst be important in the generation of new energetically more favourable conjugated previously developed by the Fürstner group. drug targets. Fürstner and co-workers, system — so identification of a mild The selectivity of this catalyst for reaction however, were most interested in the synthetic method was important. Fürstner with two methyl-alkynes in the presence unusual structure, which contains a and co-workers first developed a mild gold- of three other alkenes is remarkable. The 4-hydroxypyrone as part of a macrocycle catalysed method for the construction of synthesis was completed by a selective (pictured). Restricted rotation of this 4-hydroxypyrones. To construct the natural reduction of the alkyne resulting from this moiety (blue) in combination with product, however, it was necessary to use metathesis and a final deprotection to the single stereocentre (of unknown the new cyclization method on a substrate remove an acetyl group introduced during configuration) means that the compound containing no less than six carbon–carbon pyrone formation. SD

592 NATURE | VOL 4 | AUGUST 2012 | www.nature.com/naturechemistry

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