Spotlights Cite This: J. Am. Chem. Soc. XXXX, XXX, XXX−XXX
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Spotlights on Recent JACS Publications
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DEATH-CAP MUSHROOM TOXIN CAPITULATES TO TOTAL SYNTHESIS α-Amanitin is a bicyclic octapeptide produced by the “death-cap” mushroom (Amanita phalloides) that is exceptionally toxic for its ability to inhibit RNA polymerase II, one of the enzymes that catalyzes the transcription of DNA. The well-studied peptide and its analogues have potential applications as chemotherapeutic agents, which has increased the demand for α-amanitin and motivated the pursuit of synthetic methods for its production that bypass extracting small amounts from mushrooms and are not reliant on existing, low-yielding fermentation-based processes. David M. Perrin and co-workers have now described the first total synthesis of α-amanitin, providing a scalable route for accessing the natural product (DOI: 10.1021/jacs.7b12698). As a key step in the synthesis, the researchers employ a fluoropyrroloindoline as an electrophilic intermediate that creates the tryptathionine cross-link responsible for the bicyclic structure. They also identify a solvent-dependent tryptathionine sulfoxidation method that selectively produces the (R)- or (S)sulfoxide final products. Cytotoxicity studies conducted on these diastereomers reveal that the (R)-sulfoxide (α-amanitin) is 8 times as toxic as the (S)-sulfoxide. The convergent nature of the new synthetic route could enable production of an array of αamanitin derivatives that were not previously available from a biosynthetic pathway, for structure−activity relationship studies. Elizabeth Meucci
EXCITED-STATE MOLYBDENUM−DINITROGEN COMPOUNDS IN THE SPOTLIGHT Metal catalysts that can stitch together nitrogen and hydrogen gases to produce ammonia are a valued part of the industrial process for making fertilizer. Inspired by the metal centers in plant enzymes that fix nitrogen, researchers are studying molybdenum compounds that coordinate nitrogen in an effort to develop more renewable, energy-efficient pathways to ammonia. One recently prepared molybdenum complex contains dinitrogen sandwiched between two metal atoms. Although this bridging coordination mode is inert in the complex’s electronic ground state, it might become reactive in an excited state after the terpyridine ligands attached to each molybdenum absorb ultraviolet to near-infrared light. Paul J. Chirik, Gregory D. Scholes, and their colleagues have studied the nature and lifetime of the excited states of this molybdenum−nitrogen complex using ultrafast spectroscopy (DOI: 10.1021/jacs.8b00890). As the excited complex relaxes, electrons move from the ligand to the metal−nitrogen bridge. This electron density shift may make the nitrogen more basic and nucleophilic, and may ultimately open pathways for N−H bond formation. Understanding how the molecular structure relates to its excited-state dynamics could help researchers modify the ligands to increase the lifetime of the reactive state for turning on new reactivity. Melissae Fellet, Ph.D. STRUCTURAL ISOMER DIFFERENTIATION BY QUANTUM INTERFERENCE SWITCHING Structural isomer differentiation at the single-molecule level, once unthinkable, is now possible. The technique remains difficult yet is important for developing applications such as single-molecule circuits. Wenjing Hong, Hao-Li Zhang, and coworkers have now found a way to use two existing methods in isomer differentiationquantum interference and stimuli responsein tandem to accomplish what has only been theoretically suggested: a reversible quantum-interference molecular design. They achieve single-molecule diketopyrrolopyrrole isomer identification using the mechanically controllable break junction technique (DOI: 10.1021/jacs.8b02825). Diketopyrrolopyrrole, an organic dye important in optoelectronics, produces two structural isomer derivatives, SDPP and SPPO, upon alkylation. The isomers exhibit similar conductivity measurements despite differing in alkyl substituent placement. The researchers use camphorsulfonic acid to protonate the free nitrogen atom in SPPO, which causes an order of magnitude conductance change at the molecular junction along with a spectroscopically measurable color change. Upon addition of trimethylamine base for deprotonation, the conductance returns close to the original level. Underlying this on/off halochromic switch, protonated SPPO has two possible
NEW SEMICRYSTALLINE POLYMER READILY MADE For decades, synthetic chemists have been interested in transforming simple and readily available hydrocarbon monomers into complex polymers with highly ordered structures. However, the set of materials available from the stereoselective insertion polymerization of common alkenes is limited, and many were made more than half a century ago. Designer metal catalysts that can perform “chain-walking”, resulting in new branched polymers, allow new opportunities to synthesize new precision polymer architectures. Researchers led by Geoffrey Coates describe the creation of a new semicrystalline polymer from 1-butene with the assistance of new nickel chain-walking catalysts (DOI: 10.1021/jacs.8b02963). The new polymer is isotactic, with an ordered arrangement of pendant methyl groups of the same relative stereochemistry along the hydrocarbon chain. Oftentimes, chain-walking results in scrambling of the substituent groups that disrupts polymer crystallinity. However, the researchers find their system to be a rare example of stereoretention in a chain-walking polymerization process. The success of the system is owed to the high level of stereo- and regiochemistry of the catalyst, along with precise chain-walking to the methyl group of the monomer. The team says additional catalyst development is under way to increase the selectivity of the process even further. Christine Herman, Ph.D. © XXXX American Chemical Society
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DOI: 10.1021/jacs.8b04959 J. Am. Chem. Soc. XXXX, XXX, XXX−XXX
Journal of the American Chemical Society
Spotlights
resonance structures: linearly conjugated and cross-conjugated forms. The proton favors the cross-conjugated form, which results in destructive quantum interference and, therefore, poor conductance. This novel technique has the potential to enable recognition of single molecules as well as conductivity shifts in molecular electronics. Kristy G. Lahoda, Ph.D.
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DOI: 10.1021/jacs.8b04959 J. Am. Chem. Soc. XXXX, XXX, XXX−XXX
