SYNTHESIS
A sweet hookup Macrocyclic catalyst stereospecifically builds β-glycoside sugar linkages
lyst activates an alcohol to make it a better nucleophile. The team used the catalyst to assemble a wide variety of trans-1,2-, cisAssembling oligosaccharides and polysacreaction of a glycosyl chloride to create 1,2-, and 2-deoxy-β-glycosides. charides can be tricky business. The steric oligosaccharides. But the team discovered “There’s no reliable, general way to atand electronic elements that come into that when using a macrocyclic bis-thiourea tach any two sugars together in a predictable play when hooking one sugar onto another catalyst, both enantiomers of the catalyst way,” Jacobsen says. “That’s key if we’re gomakes the synthesis of these molecules unled to the same stereochemical outcome in ing to help advance the field of oligosacchapredictable. Now, inspired by the enzymes the product. ride synthesis, including automated meththat connect sugars to one another in cells, Instead of the catalyst controlling the ods, for biological applications.” This new Eric N. Jacobsen and coworkers at Harvard stereochemistry of the reaction, the stereo- catalyst, he says, is a step in that direction. University have developed a macrocyclic chemistry of the sugar controls the reac“This is a fascinating study that links catalyst that predictably and reliably builds tion, Jacobsen explains. The reaction takes concepts from numerous parts of chemistry certain types of sugar linkages—known as place via an SN2 mechanism: The to define a new approach to selective carboβ-glycosidic bonds—in a stereospecific thiourea groups in the catalyst hydrate synthesis,” says Scott J. Miller, an manner (Science 2017, DOI: 10.1126/science. make hydrogen bonds to the expert in organic syntheCF3 aal1875). chloride on the sugar to sis at Yale University. N O Jacobsen’s group was hoping to use its make it a better leaving “Achieving catalyst S expertise in chiral catalysts to influence the group, while an amide control with nonenO zymatic catalysts, stereochemical outcome of a substitution side chain in the cataN N H H through the use of O OCH3 OCH the reported bis3 OCH3 Bis-thiourea Cl CH3O OCH3 thioureas, opens O catalyst H H O O CH3O up new doors and + CH3O N N O BnO O CH3O O leverages the physO BnO OBn HO S O ical organic chemBnO N BnO OBn istry of the catalytic Bn = benzyl CF3 mechanisms in powerful new ways.”—BETHANY A macrocyclic bis-thiourea catalyst allows the Jacobsen group
Carbohydrate connection to create a ß-glycoside.
Bis-thiourea catalyst
HALFORD
BIOBASED MATERIALS
Process mimics spider silk spinning
CREDIT: NAT. CHEM. BIOL.
Combining parts of silk proteins from different spider species improves production of artificial silk Spider silk is prized for its strength. But researchers led by Anna Rising and Jan Jospiders don’t make enough of the tough hansson of the Swedish University of Agrifibers to harvest for industrial uses. So recultural Sciences and the Karolinska Instisearchers and biotech tute has now come up with firms have turned to A nest of spun fibers made a process for making silk bioengineering silk with from a chimeric recombinant that more closely mimics genetically modified spider silk protein. what spiders do (Nat. Chem. cells or animals. These Biol. 2017, DOI: 10.1038/ methods produce wanchembio.2269). ter-insoluble silk proSpider silk proteins are teins, which then need made of an N-terminal doto be spun into fibers in main and a C-terminal dothe presence of harsh main bracketing a region of solvents—a process repeated amino acids, which quite unlike the one spigives the silk its strength. ders use. “The N-terminal domains A team of Swedish are generally quite water
soluble, but some C-terminal domains aren’t very soluble at all,” Johansson says. To make their artificial silk, the researchers used the N-terminal and repetitive regions from one spider species and a relatively water-soluble C-terminal region from another species. The team then engineered bacteria to produce the protein, which was soluble at concentrations as high as 500 mg/mL. To “spin” nearly a kilometer of silk fiber, the researchers pumped a pH 7.5 solution of their protein through a glass capillary into a pH 5 aqueous buffer, mimicking the process spiders use, where the low pH in a spider’s spinning ducts helps trigger fiber assembly. Spider silk expert Randy Lewis of Utah State University says the team’s use of a pieced-together silk sequence was novel, but “it remains to be seen” if it will work for spider proteins with longer repetitive regions.—CELIA ARNAUD JANUARY 16, 2017 | CEN.ACS.ORG | C&EN
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