8578 Chem. Commun., 2013, 49, 8578--8582 This journal is c The Royal Society of Chemistry 2013

Cite this: Chem. Commun.,2013,49, 8578

Highlights from the 48th EUCHEM conference onstereochemistry, Burgenstock, Switzerland, May 2013

Gonçalo J. L. Bernardes*ab

Recognizing known faces of possiblespeakers at the train station is usuallyhow the journey to the outstandingBurgenstock conference starts, now heldin the majestic village of Brunnen,Switzerland (Fig. 1). Tradition dictatesthat the programme remains a mysteryuntil the beginning of the conference andthat speakers can only give one plenarylecture during their life-time. The confer-ence is characterized by a well-balancedblend of scientists from both academiaand industry and participants (roughly 100)are requested to stay for the whole week.Every year since the 1st edition back in1965, the Burgenstock gathers 14 of theworld’s leading scientists within thechemical sciences to present theirresearch under the inspirational viewsof the Swiss Alps (Fig. 1).

President Luisa de Cola (Universite deStrasbourg and Karlsruhe Institute ofTechnology) together with the local orga-nising committee constituted of Alain DeMesmaeker (Syngenta Crop ProtectionResearch, Stein), Jerome Lacour (Univer-sity of Geneva), Reto Naef (NovartisPharma AG, Basel), Philippe Renaud(University of Bern) and Helma Wennemers(ETH Zurich) undertook the challenging

job of putting together the scientificprogramme of the 2013 edition as wellas an entertaining set of social activities.While stereochemistry was at the centreof the Burgenstock meeting, today’sscientific program covers a wide rangeof fundamental aspects within thechemical sciences as well as interdisci-plinary approaches that, importantly, areproviding a path toward collectivelyaddressing the many challenges ofchemistry. These efforts were translatedinto a diverse and rich scientificprogram, the highlights of which aredescribed in this report.

The President opened the conferenceby welcoming the participants andpresenting the Guest of Honor ofthe 48th EUCHEM conference on

stereochemistry, David Reinhoudt (TwenteUniversity). This was followed by high-lights of the conference proceduresand the promise of chocolate duringthe lectures, given the President is aconfessed chocolate lover. Of course,the President offered the responsibilityfor the weather to the Vice-PresidentAntonio Echavarren (Institute ofChemical Research of Catalonia), whodid a great job keeping the rain awayfrom Brunnen during most of the con-ference. The conference had officiallystarted and a banquet dinner precededthe first evening lecture.

The scientific program started with afascinating lecture by Michael Gratzel(EPFL Lausanne) after an original intro-duction involving ‘‘explosions and flames’’

Fig. 1 Panoramic picture of the inspirational Brunnen. Photo credit: Martina Steiner.

a Department of Chemistry, University of Cambridge,

Lensfield Road, Cambridge, CB2 1EW, UK.

E-mail: gb453@cam.ac.ukb Instituto de Medicina Molecular, Faculdade de

Medicina da Universidade de Lisboa,

Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal.

E-mail: gbernardes@fm.ul.pt

DOI: 10.1039/c3cc90259e

www.rsc.org/chemcomm

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by Katharina Fromm (University ofFribourg). The quest for cleaner energyand more efficient energy storage methodsis likely one of the major challenges ourworld faces. Michael Gratzel pioneeredthe development of energy conversionsystems by using mesoscopic materials.He took us on an incredible journeystarting with the first prototype of adye-sensitized nanocrystal cell (DSC) in1988 and its publication in 19911 totoday’s integrated photovoltaic glasspanels. By covering the surface of meso-scopic oxide films with an appropriatemolecular chromophore it is possible toefficiently harvest and convert sunlightinto electricity. With today’s currentimproved DSC, solar-to-electric power-conversion efficiency (PCE) under fullsunlight can reach values above 13%.2

The second day of the Burgenstockmeeting began with two lectures onmaterials bioengineering. Jeffrey Hubbel(EPFL Lausanne) demonstrated on howmaterials and proteins may be engineeredto precisely modulate cellular responses.3

The power of these strategies were under-scored by impressive applications intissue engineering and immunology.For example, a simple and efficientsystem was designed and constructedby engineering the growth factor micro-environment with fibronectin domainsthat resulted in wound and bone tissuehealing.4 In the immunotherapeuticscontext, small antigen modified nano-particles were shown to effectively targetantigen-presenting cells after pulmonaryadministration. This led to induction of apotent immune response in the lung andat other mucosal surfaces, conferringprotection against viral infections suchas influenza.5

Still on materials engineering, HeatherMaynard (UCLA) illustrated how to buildbiomimetic polymers and smart polymersfor drug-delivery purposes. The inherentinstability of basic fibroblast growthfactor (bFGF), a protein that displays keyroles in a number of essential cellularprocesses, during storage and deliveryhas limited its therapeutic application.By covalent conjugation with a heparin-mimicking polymer, a copolymer consistingof styrene sulfonate units and methylmethacrylate units bearing poly(ethyleneglycol) side chains, it was possible to

stabilize bFGF while retaining its bio-logical activity, a significant step towardsits clinical use.6 Furthermore, theMaynard research group has reportedthe synthesis of trehalose side chainpolymers for stabilization of proteinconjugates to environmental stressors.When conjugated to proteins, the trehalosepolymers significantly increased stabilitytoward lyophilization and heat whileretaining the native protein activity.Finally, the glycopolymers were comparedto equivalent concentrations of trehalosealone and poly(ethylene glycol) (PEG) andfound to be superior at stabilizing theprotein to lyophilization and heat.7

The afternoon brought an excitingposter session which was preceded by5 short lectures that served as‘‘appetizers’’. Poster sessions at Burgenstockare an excellent stage for discussion andinteractions between junior and seniorscientists, and academics and industryparticipants. The short lectures werepresented by some of Europe’s mostpromising young scientists: Beat Fierz(EPFL Lausanne), Matthew Fuchter(Imperial College), Franziska Schoenebeck(ETH Zurich), Jan Streuff (Albert-Ludwigs-Universitat Freiburg) and Mariola Tortosa(Universidad Autonoma de Madrid).

The evening lecture was given byDennis Curran (University of Pittsburgh)who shared is work on fluorous mixingsynthesis for the construction of small-libraries of complex natural productstereoisomers in single form. By fluoroustagging of reactants, products can laterbe demixed based on the fluorine

content. Recently, his research grouphas improved this technique throughthe use of binary encoding such that atotal of four tags can be employed tolabel in a unique manner a librarycontaining all 16 diastereomers of naturalproducts macrosphelides A and E. Whilethe structures of macrosphelides A and Eare known, the library data enableddetermination of the correct stereo-structure of macrosphelide D.8

The next morning was reserved torecent developments in C–C and C–Fbond formation reactions. MichaelKrische (University of Texas at Austin)gave a outstanding lecture on theformation of C–C bonds under hydro-genation and transfer hydrogenationconditions and how these were capitalisedin the total synthesis of the challengingnatural products 6-deoxyerythronolide B9

and bryostatin 7.10 Eight and five C–Cbonds formed using hydrogenativemethods were used for the synthesis of6-deoxyerythronolide B and bryostatin 7,respectively. He also presented theimpressive direct redox-triggered C–Ccoupling of alcohols and butadiene thatresults in the formation of carbonylcrotylation products with high levels ofanti-diastereoselectivity and enantio-selectivity in the absence of stoichio-metric by-products (Fig. 2A).11 Advancesin C–C bond forming reactions willsignificantly facilitate the access toand the biological evaluation of complexpolyketides.

The second lecture of the morningwas presented by Veronique Gouverneur

Fig. 2 (A) Direct stereoselective butadiene mediated crotylation. (B) A substrate umpolung strategy for theor the radiochemical synthesis of aryl fluorides (ref. 13). L = 2-amino-4,6-dihydroxypyrimidine.

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(University of Oxford) who gave aninsightful overview of the importance oflabeling strategies with the unnaturalradionuclide 18F, which is particularlysuited for use with imaging methodssuch as positron emission tomography(PET).12 While methods for fluorineincorporation are available and havebecome routinely used by medicinalchemists for the precise tuning andprobing of the properties of smallmolecule binders, few such methodscan be translated into ‘‘hot’’ conditions.Veronique Gouverneur presented majoradvances in her lab for the efficientincorporation of 18F into small moleculesincluding, for example, a metal-freeumpolung strategy that enables oxidativefluorination of electron-rich aromaticcompounds using [18F]fluoride, with theoxidation event targeting the electron-rich substrate (aryl umpolung) rather thanthe [18F]fluoride (Fig. 2B).13 The method israpid enough—18F has a half-life of 109.7minutes—allowing subsequent palladium-mediated Suzuki–Miyaura coupling of2-bromo-4-[18F]fluorophenol with benzyl-boronic acid. These methods and othersare currently applied for the production of18F labelled probes for (pre)clinical appli-cations and to accelerate drug discover.12

After lunch, and with the afternoonfree, many participants took theopportunity to hike the surroundingmountains with stunning views acrossLake Lucerne and the Swiss Alps.And in accordance with tradition, there

was no lecture scheduled for thisevening, but instead an after-dinnermusical concert by Pilar (vocals), FedericoFerrandina (guitar) and Andrea Colella(double bass) which was followed by aget-together with the musicians.

The morning of the fourth conferenceday led us into the world of materialsscience and began with a spectacularlecture by Christoph Weder (Universityof Fribourg) on the design of polymerswith specific molecular parameterswhich confer specific macroscopicproperties. In particular, the dynamicnature of non-covalent bonds has beenexplored to construct polymers that canbe influenced in a predictable manner byexposure to predefined external stimuli.Christoph Weder exemplified the powerof this approach when he discussedmetallosupramolecular stimuli-responsivepolymers in which scratch damages can behealed upon exposure to ultraviolet light(Fig. 3).14 He also presented recentdevelopments on optically healable nano-composites based on a telechelic poly-(ethylene-co-butylene) functionalised withhydrogen-bonding ureidopyrimidone(UPy) groups at the termini, and cellulosenanocrystals decorated with the samebinding motif.15 This design affordsmaterials that display high stiffness andstrength, and permit rapid and efficientoptical healing.

This was followed by a lecture fromGianluca Farinola (University of Bari),who described his research group’s

efforts in combining active organic andorganometallic molecules and polymerswith biological or inorganic nano-structures to build photo/electro-activearchitectures for applications rangingfrom organic photonics and electronicsto biology. For instance, conjugation ofpolymers bearing a fluorinated backbonewith organometallic complexes hasresulted in electroluminescent materialswith improved properties for organiclight emitting diodes (OLEDs).16

The evening session saw a dramaticshift in focus from materials to enantio-selective synthesis, with an insightfullecture by Huw Davies (Emory University)on carbenoid chemistry. The lecturestarted with an introduction of the centerfor selective C–H functionalisation(CCHF) (Fig. 4A). This pioneering initia-tive aims to promote joint efforts in thedevelopment of methods that enableselective functionalisation of traditionally‘‘unactivated’’ C–H bonds and theiruse to accelerate programmes in drugdiscovery or materials science. This wasfollowed by recent examples that resultedfrom collaborative work between differentresearch groups at the CCHF. The first,from the groups of Huw Davies andJin-Quan Yu (Scripps Research Institute),consisted of consecutive rhodium-catalysed enantioselective intermolecularC–H insertion followed by palladium-catalyzed C–H activation/C–O cyclisationto access 2,3-dihydrobenzofurans. Thesecan then be further elaborated by asubsequent palladium-catalyzed inter-molecular Heck-type sp2 C–H functional-isation to provide the core of theLithospermic acid natural product(Fig. 4B).17 Additionally, combined syn-thetic and computational studies fromthe groups of Huw Davies and DjamaladdinMusaev (Emory University) not onlyshowed that aryldiazoacetates andvinyldiazoacetates undergo highly enantio-selective cyclopropanations with electron-deficient alkenes, but also provided keyinsights that may lead to novel rhodium-catalysed carbenoid reactions.18

Thursday’s proceedings were dedi-cated to the field of chemical biologybeginning with Nicolas Winssinger(University of Geneva) who gave an enga-ging overview of nucleic acids templatedreactions and their use for programming

Fig. 3 Schematic representation of optically healable supramolecular nanocomposites based on a telechelicpoly(ethylene-co-butylene) functionalised with hydrogen-bonding ureidopyrimidone (UPy) groups at thetermini, and cellulose nanocrystals decorated with the same binding motif. Also shown are AFM images of adeliberately damaged and an optically healed sample.15 Image courtesy of Mahesh Biyani, University ofFribourg.

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self-assemblies in chemical biology. Anumber of methods are now availableto access nucleic acid-tagged librariesand to select the most promisingcompounds within such libraries. TheWinssinger group has focused on thedevelopment of PNA-tagged smallmolecules that are displayed on DNAtemplates (Fig. 5A).19,20 This strategyhas shown valuable utility for screeningpurposes,20 but also to probe the optimalgeometry in multivalent interactions.This was the case of a nucleic acid-encoded carbohydrate library that led tothe identification of consensus DC-SIGNbinder motif which when placed in adendrimer shows enhanced binding togp120’s.21

Subsequently, Tom Muir (PrincetonUniversity) described his fascinatingwork on chromatin, a complex of DNAand proteins that act as a dynamicsignaling platform controlling genefunction. Muir’s group has expandedsignificantly the chemical tools availableto install post-translational modifica-tions (PTMs) and their analogs intopre-determined sites on histone pro-teins, the primary protein componentsof chromatin, enabling their study in

genetic regulation.22 Fig. 5B illustrateshow to tracelessly link two syntheticpeptides or a peptide and an expressedprotein, respectively, with one of thembearing a pre-installed modification,by native chemical ligation (NCL) andexpressed protein ligation (EPL). Withthis strategy many types of PTMshave been incorporated into histonesenabling the study of their precise rolesin genetic regulation.22 Impressive workhas recently led to the discovery thatpediatric diffuse intrinsic pontine gliomas(DIPGs) contain a missense K-to-Mmutation leading to gain-of-functionand inhibition of the enzymatic activityof Polycomb repressive complex 2 (PRC2).This result strongly supports thataberrant epigenetic silencing throughH3K27M-mediated inhibition of PRC2activity is responsible for promotion ofgliomagenesis.23

Thursday afternoon was again reservedfor 5 short lectures by young independentscientists: Gonçalo Bernardes (Universityof Cambridge and Instituto de MedicinaMolecular, Lisbon), Micha Fridman (TelAviv University), Seiji Shirakawa (KyotoUniversity), Boris Vauzeilles (CNRS andUniversite Paris-Sud) and Sandeep Verma

(Indian Institute Of Technology-Kanpur)which was followed by an exciting andintense poster session.

Viola Vogel (ETH Zurich) concludedthe day by showing how her researchgroup is decoding the underlyingmechanisms behind bacteria and cellresponses to mechanical stimuli andhow these are converted into bio-chemical signals that can switch cellfunctions.25 As an example of a mecha-nical chemical switch, it was demon-strated that mechanical stretching offibronectin fibres present in the extra-cellular matrix (ECM) are sufficientto physically destroy a cell-binding siteproviding insights on how the mechano-biology of ECM might regulate bacterialand cell-binding events during infection.26

This year’s Vice-President and conse-quently the next President, AntonioEchavarren chaired the last section ofthe conference on Friday morning. First,Jun-Ichi Yoshida (Kyoto University) gavean insightful lecture on how to integrateorganic synthesis on the basis of reactiveintermediates to build organic moleculesunder flow chemistry.27 The approach isbased on the so-called ‘‘cation-poolmethod’’ that consists of rapid genera-tion of reactive organic cations in theabsence of nucleophiles and subsequentreaction with nucleophiles before theydecompose using an integrated flowmicroreactor system. This methodenables, for instance, performing glyco-sylation reactions under flow28 and led tothe development of a number of novelelectrochemical organic reactions includ-ing electrochemical C–H amination29 foruse in flow chemistry. The final scientificlecture was given by Bruno Chaudret(University of Toulouse) on the constructionof organometallic-based nanoparticlesand their uses.30 While still limited to asmall number of organometallic pre-cursors, Bruno Chaudret showed usexamples of nano-objects built with pre-cise control of both the growth and of thesurface chemistry. With these particles ofdefined shapes, organisation and surfacechemistry as well as physical propertiesare formed enabling their use in asym-metric catalysis and microelectronics.30

The president of the organisingcommittee, Luisa de Cola, closed themeeting by thanking the lecturers and

Fig. 4 (A) Schematic representation of the structure of the center for selective C–H functionalization. Imagecourtesy of Huw Davies. (B) Consecutive C–H functionalization reaction for the enantioselective synthesis ofelaborated 2,3-dihydrobenzofurans.

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poster presenters for stimulating scienti-fic presentations, the participants forcontributing in exciting discussions, thecolleagues of the organising committeefor their assistance in the organisation,the students for their help with thetraditional discussions after the lecturesand the Seehotel Waldstatterhof staffmembers. Collectively all made the 48thBurgenstock a memorable experience.The 49th Burgenstock will be heldfrom the 4–9th of May 2014 and AntonioEchavarren will have the challengingtask of matching the high qualityof preceding conferences. As traditionsuggests, the 2014 conference willcertainly be as fascinating and stimu-lating and participation is highlyrecommended.

G.J.L.B. is a Royal Society UniversityResearch Fellow at the Department of

Chemistry, University of Cambridge anda Principal Investigador FCT at the Insti-tuto de Medicina Molecular, Faculdadede Medicina da Universidade de Lisboa.G.J.L.B. thanks the organising committeefor the opportunity be part of the Burgen-stock Stereochemistry conference and fora JSP Fellowship in 2011.

Notes and references1 B. O’Regan and M. Gratzel, Nature, 1991,

353, 737–740.2 A. Yella, H.-W. Lee, H. N. Tsao, C. Yi,

A. K. Chandiran, M. K. Nazeeruddin,E. W.-G. Diau, C.-Y. Yeh, S. M.Zakeeruddin and M. Gratzel, Science,2011, 334, 629–634.

3 J. A. Hubbell and A. Chilkoti, Science, 2012,337, 303–305.

4 M. M. Martino, F. Tortelli, M. Mochizuki,S. Traub, D. Ben-David, G. A. Kuhn,R. Muller, E. Livne, S. A. Eming andJ. A. Hubbell, Sci. Transl. Med., 2011,3, 100ra189.

5 C. Nembrini, A. Stano, K. Y. Dane,M. Ballester, A. J. van der Vlies,B. J. Marsland, M. A. Swartz and J. A.Hubbell, Proc. Natl. Acad. Sci. U. S. A.,2011, 108, E989–E997.

6 T. H. Nguyen, S.-H. Kim, C. G. Decker,D. Y. Wong, J. A. Loo and H. D. Maynard,Nat. Chem., 2013, 5, 221–227.

7 R. J. Mancini, J. Lee and H. D. Maynard,J. Am. Chem. Soc., 2012, 134, 8474–8479.

8 D. P. Curran, M. K. Sinha, K. Zhang,J. J. Sabatini and D.-H. Cho, Nat. Chem.,2012, 4, 124–129.

9 X. Gao, S. K. Woo and M. J. Krische, J. Am.Chem. Soc., 2013, 135, 4223–4226.

10 Y. Lu, S. K. Woo and M. J. Krische, J. Am.Chem. Soc., 2011, 133, 13876–13879.

11 J. R. Zbieg, E. Yamaguchi, E. L. McInturff andM. J. Krische, Science, 2012, 336, 324–327.

12 M. Tredwell and V. Gouverneur, Angew.Chem., Int. Ed., 2012, 51, 11426–11437.

13 Z. Gao, Y. H. Lim, M. Tredwell, L. Li,S. Verhoog, M. Hopkinson, W. Kaluza,T. L. Collier, J. Passchier, M. Huiban andV. Gouverneur, Angew. Chem., Int. Ed.,2012, 51, 6733–6737.

14 G. L. Fiore, S. J. Rowan and C. Weder,Chem. Soc. Rev., 2013, 42, 7278–7288,DOI: 10.1039/c3cs35471g.

15 M. V. Biyani, E. J. Foster and C. Weder, ACSMacro Lett., 2013, 2, 236–240.

16 G. M. Farinola and R. Ragni, Chem. Soc.Rev., 2011, 40, 3467–3482.

17 H. Wang, G. Li, K. M. Engle, J.-Q. Yu and H.M. L. Davies, J. Am. Chem. Soc., 2013, 135,6774–6777.

18 H. Wang, D. M. Guptill, A. Varela-Alvarez,D. G. Musaev and H. M. L. Davies, Chem.Sci., 2013, 4, 2844–2850.

19 K. Gorska and N. Winssinger, Angew.Chem., Int. Ed., 2013, 52, 6820–6843.

20 J. P. Daguer, M. Ciobanu, S. Alvarez,S. Barluenga and N. Winssinger, Chem.Sci., 2011, 2, 625–632.

21 M. Ciobanu, K.-T. Huang, J.-P. Daguer,S. Barluenga, O. Chaloin, E. Schaeffer, C. G.Mueller, D. A. Mitchell and N. Winssinger,Chem. Commun., 2011, 47, 9321–9323.

22 B. Fierz and T. W. Muir, Nat. Chem. Biol.,2012, 417–427.

23 P. W. Lewis, M. M. Muller, M. S. Koletsky,F. Cordero, S. Lin, L. A. Banaszynski,B. A. Garcia, T. W. Muir, O. J. Becher andC. D. Allis, Science, 2013, 340, 857–861.

24 N. Winssinger, Artif. DNA: PNA XNA, 2012,3, 105–108.

25 I. Schoen, B. Pruitt and V. Vogel, Annu.Rev. Mater. Res., 2013, 43, 589–618, DOI:10.1146/annurev-matsci-062910-100407.

26 M. Chabria, S. Hertig, M. L. Smith andV. Vogel, Nat. Commun., 2010, 1, 135.

27 J.-i. Yoshida, H. Kim and A. Nagaki,ChemSusChem, 2011, 4, 331–340.

28 K. Saito, K. Ueoka, K. Matsumoto, S. Suga,T. Nokami and J.-i. Yoshida, Angew. Chem.,Int. Ed., 2011, 50, 5153–5156.

29 T. Morofuji, A. Shimizu and J.-i. Yoshida,J. Am. Chem. Soc., 2013, 135, 5000–5003.

30 B. Cormary, F. Dumestre, N. Liakakos,K. Soulantica and B. Chaudret, DaltonTrans., 2013, DOI: 10.1039/c3dt50870f.

Fig. 5 Two approaches in Chemical Biology: (A) schematic representation of DNA display of PNA-taggedmolecules. Figure adapted from ref. 24. (B) Chemical approaches for the incorporation of PTMs and theiranalogs into histone proteins for the study of genetic regulation. Figure adapted from ref. 22.

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