CONFERENCE REPORT 525

doi:10.2533/chimia.2008.525 CHIMIA 2008, 62, No. 6 CONFERENCE REPORT

Chimia 62 (2008) 525–528 © Schweizerische Chemische Gesellschaft ISSN 0009–4293

The 43rd EUCHEM Conference on Stereo- (Bürgenstock Conference 2008) Fürigen, April 12–18, 2008

Hermann Wegner*a and Andreas Zumbuehl*b

In an ever changing, metastable world of Don Hilvert (ETH Zürich) presided helped to shape generations of , science and technology it is good to know over the symposium which attracted scien- planting the seed of curiosity deep within of facts that will never change. For decades tists from 22 countries. We all were curi- them together with an indestructible confi- now, the Bürgenstock Conference in spring ous what line-up of speakers the president dence in the power of organic synthesis. has been such an anchor-point, a week to had prepared together with vice-president step back and have a look at chemistry in Ben L. Feringa (University of ) its pure and applied forms. A week to be and his organizing committee: François amongst people that speak the same lan- Diederich (ETH Zürich), E. Peter Kündig guage, a week to refocus one’s view of cur- (University of Geneva), Klaus Müller (F. rent science. Hoffmann-La Roche, Basel), Philippe Re- This year’s Bürgenstock conference naud (University of Berne), and Jay Siegel has passed already, leaving the participants (University of Zürich). The dinner on Sat- with the slightly melancholic impression of urday evening was thus left with satisfied having been a part of an important event in people looking forward to an exceptional chemistry. week to come.

Dieter Seebach

On an easy early spring Sunday morn- ing – at nine o’clock sharp − Prof. Schwarz opened with Swiss ‘Pünktlichkeit’ the sci- entific part of the 43. Bürgenstock confer- ence. The honor of the first lecture was given to Jérôme Lacour (University of Ge- neva), who set the standard for this meeting a b * Correspondence: Dr. H. Wegner , Dr. A. Zumbuehl Don Hilvert a Department of with a fulminant talk about chiral in University of Basel asymmetric synthesis. He developed with St. Johanns-Ring 19 his coworkers helical chiral phosphonate CH-4056 Basel The first pleasant surprise was meeting anions. As counter with metal salts they E-Mail: [email protected] b Department of Organic Chemistry this year’s guest of honour, Dieter Seebach create a chiral environment, which Jérôme University of Geneva (ETH Zürich) one of the corner stones of demonstrated in thoroughly designed NMR 30, quai E. Ansermet current synthetic chemistry. Through his experiments. Application of his TRISPHAT CH-1211 Genève 4 E-Mail: [email protected] impressive list of contributions, he has counterion in the first asymmetric 1,2-Ste- CONFERENCE REPORT 526 CHIMIA 2008, 62, No. 6 vens rearrangement proved that this is using acetaldehyde in enamine . cinogenicity and the need for an additional not just an exercise of theoretical intent. In the last part of his talk, Ben presented proofreading mechanism in humans by e.g. Additionally, he designed a highly selec- his new concept of asymmetric counterion MutSα . With the latter, Lorena crossed the tive catalyst for an asymmetric Carroll- directed catalysis (ACDC), which will not bridge to human systems, opening new rearrangement, based on a RuCp-complex only ‘rock’ the organocatalytic community. fields in cancer therapy. in combination with chiral Schiff base li- He showcased the concept in, for example, gands. An interesting observation on the an asymmetric epoxidation. aging of the catalytic species led Jérôme to discover new air stable catalysts that were As spectacular as the first day started it end- easily separable by column chromatogra- ed with a blooming presentation by Roman phy on silica . Kaiser (Givaudan) capturing the ‘Scents of the Vanishing Flora’. For over 30 years, as stated by the moderator Lia Addadi, he has been tracking down the bouquet of Earth’s remotest places. His latest project hunts down the odors of endangered plants, col- lecting samples of over 2500 species. In his lecture, he took an awed audience on a trip around the world of olfactory experiences, illustrated by distributed perfumers testing strips. We learned about Dracula chester- tonii (that not only mimics the shape of a fungus, but also its smell), or the desert gold Lorena S. Beese plant from Death Valley that produces chlo- rinated phenols originating from the soil’s high salt concentration. The complexity Moving from DNA to peptide synthesis, of smelling was demonstrated by a scent Mohamed A. Marahiel (Philipps Universi- sample of a Sauvignon Blanc Palliser Es- ty Marburg) presented his latest results on Jérôme Lacour tate 2000, an ultimate challenge for anyone non-ribosomal peptide synthesis (NRPS). working in the field. Compared to the classical ribosomal pep- tide synthesis, the NRPS is able to intro- Equally young and enthusiastic, Ben- duce a larger variety of over 450 different jamin List (MPI Mühlheim) presented his building blocks, allowing much higher lecture about new strategies and concepts complexities. Molecules like bleomycin, for catalysis. Without doubt he is one of the surfactin, cyclosporin and vancomycin are defining characters in the rejuvenated field just a few examples of the synthetic power of organocatalysis. In only a few years, he of NRPS. In order to possibly exploit this and his young group have developed asym- natural assembly line for organic synthesis, metric catalytic versions of a variety of clas- a deep understanding of its architecture and sic reactions, like aldol, Mannich, Michael, function is needed. Mohamed impressively etc. In the case of aldol condensations, he elucidated the modular structure of the sur- distinguished four modes of action: Inter- factin biosynthesis cluster from crystals molecular, intramolecular endo− endo and and NMR studies. From these results he endo− exo and finally transannular. For the was able to predict and modify the protein latter he recently published an organocata- structure in order to incorporate specific lytic asymmetric version, which he fea- amino acids during the peptide synthesis. tured in the shortest asymmetric synthesis Mohamed ended his talk with his inspir- of (+)-hirsutene. He also solved one of the Roman Kaiser ing vision of the architecture of a complete longstanding problems in organocatalysis nonribosomal assembly line.

With Don Hilvert as this year’s presi- dent, the conference promised to also high- light recent advances in biology. Indeed, Ilme Schlichting chaired the Monday morn- ing session on life’s molecular machines. Lorena S. Beese (Duke University Medi- cal Center) investigated the high-fidelity of DNA synthesis by analyzing an impressive number of crystal structures. Using a co- crystallization technique she was able to snapshot different stages of action of DNA polymerase I and the effect of the various nucleotide mismatches. Lorena further showed crystal structures with incorporated modified nucleosides (O6MeG and 8oxoG), noting the perfect fit into the natural DNA Benjamin List double helix, which explains their high car- Mohamed A. Marahiel CONFERENCE REPORT 527 CHIMIA 2008, 62, No. 6

The title of the evening promised a es a C 2 -symmetric α -diimine Ni-catalyst to The fourth science day of the meeting, sweet lecture. After an introduction by Pe- induce a living polymerization of propylene moderated by Beate Koksch , was again ter Seeberger , Ben Davis (University of to form thermoplastic elastomers. A project under the stars of biochemistry. The first Oxford) started a firework on sugar and dear to Geoffrey’s heart is the development lecture by Frances H. Arnold (California protein chemistry. Glycosylation is one of of biodegradable and environmental friend- Institute of Technology) dealt with her ‘fa- the most important posttranslational modi- ly based on CO2 monomers. He vored ’, Nature’s cytochrom P450 fications used by Nature to decorate pro- showed that Zn- and Co catalysts can form heme-mono oxygenase. Probing into the teins. Mimicking this process in the chemi- poly(propylene)carbonates. In the course of vast sequence space she was able to decou- cal laboratory will allow protein functions his research on poly(β -hydroxybutyrates) ple the enzyme from its biological context. to be finetuned. Ben’s first approach relied he discovered an intriguing insertion reac- She changed the function of cytochrom on a mixed sulfur-selenium reagent strategy tion of CO into cyclic ethers to form lac- P450 BM3 from subterminal oxidation of to site-selectively couple sugars to proteins. tones. fatty acids to the oxidation of propane using He then went on to more complex systems, directed evolution, a technique pioneered ultimately using PSGL-lacZ as an inflam- After this splendid start Kyoko Nozaki in her laboratory. She experienced the fine mation marker in a rat cortex. MRI active (University of Tokyo) stepped into her fa- line between optimizing turnover numbers GNPs allow e.g. the visualization of inflam- ther’s footsteps, who gave a lecture at the and stability of the protein. The knowledge mation in an in vivo stroke model. In order 15. Bürgenstock Conference in 1979. She obtained in that process was applied to the to selectively decorate proteins with differ- presented her work on olefin− CO co-po- oxidation of other alkanes by enzymes, as ent sugars, he developed new orthogonal lymerization catalyzed by Pd(II)-(R , S )-BI- well as the selective deprotection of per- strategies, such as methods to form sulfide NAPHOS. By carefully combining experi- methylated sugars. A now commercially bridges, cross-metathesis and click chem- mental and theoretical data she elucidated available plate with 120 mutants of P450 istry. the stepwise chain propagation mechanism. was used in her laboratory to create milli- A thorough analysis of the 3D structure of gram quantities of dozens of metabolites of these polymers revealed an equilibrium be- drug candidates in one week. tween a polyketone and a polyspiroacetal form. Using a phosphine-sulfate based li- gand on a Pd-catalyst she demonstrated the firstcoordinationpolymerizationofvinylac- etate. She finished her lecture with excerpts from her studies on boron nucleophiles and double arylation of primary amines.

Ben Davis

Frances H. Arnold The Tuesday session was chaired by Ben Feringa, preparing the grounds for two lectures on chemistry. Geoffrey After the break Homme W. Hellinga W. Coates (Cornell University) opened our (Duke University) stunned the audience eyes to the importance of with his results on computational protein not only in drugs, but also in the polymer design. Using in silico methods he re-en- bottle, in which the pill is packaged. He us- Kyoko Nozaki gineered binding sites of proteins.

The spectacular site over the lake Lu- cerne was the perfect setting for the eve- ning’s traditional chamber music evening. After the insightful introduction by Klaus Müller, we were taken back in time to the founder of modern string quartets, Joseph Haydn. His String Quartet C Major (Op. 54/2) opened the concert by the Asasello Quartet from Basel. The program contin- ued with Five Pieces for String Quartet by Erwin Schulhoff which underlined the vir- tuosity of the four young musicians. The evening was concluded by Beethoven’s String Quartet ‘Rasumowsky’ in C Major (Op. 59/3) and a short traditional piece from Geoffrey W. Coates Georgia. Homme W. Hellinga CONFERENCE REPORT 528 CHIMIA 2008, 62, No. 6

By modifying the enzyme thioredoxin to multi-step syntheses in one pot. His method contain a Zn2+ binding site he was able to also revolutionizes the way of discovering prepare an ATP-driven nanomotor. In the new reactions and reactivities by combinato- following, Homme showed an various bio- rially combining a multitude of reactants un- ranging from immobilized GSP for der different reaction conditions. In the last continuous in vivo glucose monitoring to part of his talk he investigated if Nature also detectors for warfare agents and explosives. uses this concept of DNA or RNA templated The latter he was even able to engineer into synthesis. For this reason he developed a plants. Recently, he developed an automat- methodology to extract conjugates of RNA ed ‘Protein Writing’ robot that dramatically with small molecules, identifying a variety shortens the synthesis time of proteins. of structures, e.g . RNA bound CoA, a prom- ising result to prove his theory. Ehud Keinan welcomed the evening lec- turer Kai Johnsson (EPF Lausanne), who is working on observing and manipulating proteins and their function in living cells. In Goverdhan Mehta this context, his group developed a fusion protein assay allowing to label proteins via The second talk of the morning was de- an O 6 -alkylguanine DNA alkyltransferase. livered by Justin du Bois (Stanford Univer- This SNAP-tag technology is now becoming sity). He gave the audience an idea about a standard biological technique. Kai showed the power of modern organic synthesis by time-dependent dual labeling techniques and showing a very elegant amination reaction of experiments and differentially colored the unfunctionalized C − H bonds. Carbamates as evolving segments of budding yeast. He took well as sulfonamides are suitable substrates his method to the next level by presenting for his insertion reaction catalyzed by a Rh an orthogonal CLIP-tag based on a pyrimi- catalyst. The products obtained are useful dine base.A cunningly designed experiment, buildingblocksforavarietyoffunctionalities combining SNAP and CLIP fusion proteins ( e.g . diamines) as well as starting materials allowed the monitoring of protein− protein for further reactions ( e.g. cross-coupling re- David R. Liu interactions, e.g. between p53 and Mdm2. actions). He continued his presentation with a meticulous study on the mechanism of this reaction. From those results he was able to The Bürgenstock Conference 2008 end- greatly improve the catalyst, concerning ed with a humorous summary by Klaus Mül- its stability, reactivity as well as selectivity. ler (F. Hoffmann-La Roche) picking up on He could even show first results towards an the themes of the symposium and delivering asymmetric version of the reaction. subtle stings. President Don Hilvert closed the sessions by revealing key features of the 44th EUCHEM conference of Stereochem- istry that will be held in the Seehotel Wald- stätterhof in Brunnen (the Bürgenstock Ho- tel will undergo extensive renovations until 2011). Next year’s president Ben L. Feringa will be supported by the vice-president E. Peter Kündig and the guest of honor, Klaus Müller. This will be a very special thank Kai Johnsson you to the two researchers who resigned from the organization committee (together with François Diederich ) after a combined The last day of science was opened by service of almost five decades! The new or- Samir Z. Zard , welcoming Goverdhan Meh- ganization committee will consist of Helma ta (Indian Institute of Science, Bangalore), Wennemers (University of Basel), Jérôme who gave a vivid lecture on natural product Justin du Bois Lacour (University of Geneva), Reto Näf synthesis. In his opinion, natural products (), Don Hilvert (ETH Zürich), have a locked-in co-evolutionary memory Philippe Renaud (University of Berne) and and are still the most important inspiration The grande finale of this year’s Bürgen- Jay Siegel (University of Zürich). This line- for drug discovery. He highlighted his con- stock Conference was delivered by David up in the committee promises again an out- tribution on the synthesis of polyprenylated R. Liu (Harvard University), introduced standing meeting with excellent science! acylphloroglucins (PPAPs). Starting from by Helma Wennemers . David’s lecture on simple cyclohexadiones he accessed a num- DNA-templated organic synthesis nicely Acknowledgments ber of members of the PPAPs in an elegant summarized the main topics of the meet- The authors would like to thank the Junior and efficient way. Another class of neu- ing – Biochemistry and Organic Synthesis. Scientists Participation Program and the Division rotrophically active compounds Goverdhan He encodes a specific reactivity by attaching of Chemical Research of the Swiss Chemical was interested in were the seco-prezizaane a DNA fragment to his starting materials. Society for the generous fi nancial support. The pictures of Kai Johnsson and David R. Liu were sesquiterpenes. He prepared merrilactone A Matching DNA strands will bring the reac- taken by Andrei Badoiu. in 26 linear steps. He also developed a global tive sites in close proximity increasing the ef- route to epoxyquinones which he used to pre- fective molarity by several magnitudes. With Received: April 28, 2008 pare 22 natural products in just four years. this concept he could, for example, conduct