sci e n ce/technol lot of chemistry going on in the coupling that makes it very, very difficult to achieve," Fraser-Reid explains. One problem is that the two monosaccharhe challenge of developing an effiides in sucrose "are connected to each cient, high-yielding synthesis of other at their anomeric centers by a tersucrose—common table sugar— tiary hydroxyl group. Not only is it terhas been called a Holy Grail of carbohytiary, but it is an anomeric center that is drate chemistry. Now it seems the grail capable of isomerization." has been found. The approach of Oscarson and SehThe finders are chemistry professor gelmeble is clever, Fraser-Reid says. Stefan Oscarson and grad student Fer"They set up the connecting hydroxyl nando W. Sehgelmeble of the Arrhenius group on the six-membered sugar [gluLaboratory at Stockholm University, cose]. I would never have thought that Sweden. They report a sweet achievewas possible, because the connecting hyment: the stereospecific synthesis of sudroxyl group is capable of isomerization. crose in 80% yield, about six times as high I thought it would isomerize under the reas that of any previous sucrose synthesis action conditions, but it didn't. The hy\J. Am. Chem. Soc, 122, 8869 (2000)]. droxyl group is in an orientation that is The synthesis of sucrose—involving Oscarson demonstrates one application the "simple" addition of the monosaccha- for the synthetic target of his group's new not even thermodynamically favorable. How that took place, I don't know." rides glucose and fructose—has a vener- sucrose synthesis—sweetening coffee. able history. The first chemical synthesis In addition, Fraser-Reid says, Oscarof sucrose in 1953 by the late Canadian Oscarson and Sehgelmeble have son and Sehgelmeble "have tethered tochemistry professor Raymond U. Le- now achieved a yield of 80% in the direct gether the two ends of the donor part so mieux and postdoc George Huber was re- coupling to a protected sucrose deriva- that only one possible approach is availgarded as a sensational achievement at tive, thus beating the efficiency of the able to the incoming hydroxyl group. It's the time. Sucrose was then considered Fraser-Reid and Iley synthesis by more one of the best methods for stereocontrol the Mount Everest of organic synthe- than a factor of six. Hie derivative can of glycosides. I don't know how general it sis—a synthetic target that had defied the be deprotected to give sucrose in quan- would be for ordinary oligosaccharide syntheses because it's too much trouble efforts of the world's best chemists. The titative (100%) yield. coupling yield to give a protected sucrose Asked to comment on the work, to put the tether in place. But it does solve derivative in the Lemieux and Huber syn- Fraser-Reid says: 'This is a very nice the sucrose problem in a unique way." thesis was 5.5%. Oscarson's colleague, Stockholm Unisynthesis, and it's very different from In 1975, Bertram 0. Fraser-Reid, a Le- mine and Lemieux's. It opens up a versity emeritus professor of chemistry mieux student who is now president and whole new approach to sucrose and its Per J. Garegg, calls the new procedure "a director of the Natural Products & Gly- analogs. It's a remarkable piece of most elegant and general solution to the classical problem of synthesizing (3-Dcotechnology Research Institute at Cen- work—very novel technology." tennial Campus, North Carolina State Considering that sucrose is so inex- fructofuranosides," the class of carbohyUniversity, Raleigh, and then-undergrad- pensive, is so widely available commer- drates to which sucrose belongs. When uate David E. Hey at the University of Wa- cially, and has such a simple disaccha- the methodology arose in research on terloo, Ontario, reported an improved syn- ride structure, it might seem surprising the synthesis of a carbohydrate antigen, thesis using glycal chemistry. Their yield that it's so difficult to synthesize from Oscarson and Sehgelmeble decided to in the coupling to give a sucrose analog glucose and fructose and that it has tak- test it on the classical sucrose problem. was 45%, and their overall yield to a pro- en so many decades for a high-yield syn- "Although the results hardly represent an tected sucrose derivative was about 13%. thesis to emerge. However, "there is a economic breakthrough"—because sucrose is widely available from •——™ natural sugarcane and generally does not need to be synthesized New approach produces sucrose in high yield chemically—"this is an intellectual feat," Garegg says. Crystalline glucosyl acceptor (pure cc-anomer) However, Fraser-Reid beOBn OBn OH lieves the new synthesis might O O, find some immediate applicaBnO' BnO' HO BnO BnO BnO BnO tions. "It allows you to prepare OH HO HO Deprotection Promoter t BnO the two monosaccharide part-• TBDMSO HO Quantitative 80% HO Bn ners separately, modify them, ° SCH2CH3 TBDMSO and then combine them—something the Lemieux approach and OH OH N OH TIPS" my approach do not allow," he N Sucrose TIPS^ says. This could be useful for synBridged fructofuranosyl donor (a-side blocked) thesizing biologically active sucrose derivatives, he suggests. Bn = benzyl, TBDMS =terf-butyldimethylsilyl,TIPS= tetraisopropyldisiloxane Stu Borman
Sucrose Synthesis Sets A Record
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