The Organic Chemistry of Sugars

Abstract

From ahistorical perspective, no single class of organic compounds has shared the same impact on the evolution of stereochemistry as sugar molecules.Compared with the remarkable synthesisofthe first natural product, urea, by Friedrich Wo ¨hler in 1828, the total synthesis of glucose by Emil Fischer in 1895 was ahallmark event in the annals of organic synthesis. As biological activity began to be associated with more complexnatural products such as alkaloids, steroids and various metabolitesbythe middle of the twentieth century, interest in sugars as small molecule polyols shiftedtothe study of polysaccharides and their degradation products. By the mid-1960s, synthetic carbohydrate chemistry was confined to asmall subgroup of organic chemists,who studied methods of interconversion and functional group manipulation in conjunction with the structure elucidation of antibiotics containing sugars. Soon, mostnaturally occurring sugars, including deoxy, aminodeoxy and branched ones, had been synthesized. As a result, sugar molecules had become ideal substrates to test out new bond-forming methods, particularlybecause of theirconformational properties, andthe propensity of spatially predisposed hydroxyl groups. Sugars became aplaygroundtovalidateconcepts related to anchimeric assistance in conjunction with the synthesis of aminodeoxy component sugars in various natural products. An altogether different view of sugarsand their potential as chiral building blocks was introduced in the mid-1970s. This was to have an important impact on the thought process relating to organic synthesis in general. This marked the beginninga newera of rapprochement, integrating sugarchemistry in mainstreamorganic chemistry. Notonly were the sugar components of complex natural products readily madebysynthesis, but the entire framework of the “non-sugar,” and admittedly the morechallenging part, could also be made from sugar building blocks or “chirons.” By the 1980s, the advent of reagent methodology and asymmetric synthesis once again shifted the paradigm of thinking in considering complex natural product assembly from smaller components. Today, it is more practical, in many cases, to consider other innovative approaches to total synthesis without necessarily relying on sugars as chiral,nonracemic starting materials. In fact, de novo syntheses of even raresugarsisnow possible by relyingon efficient catalytic asymmetric processes. In adifferent context, the uniquechemical and physicochemicalproperties of sugars have propelled them into new and exciting areas of application in molecular biology, drug design, materials, and other fields of direct impact on our quality of life. Arenaissance period for sugars is in full swing with the creation of new subdisciplines that bridge chemistry and biology. New areas relating to glycochemistry and glycobiology have emergedinconjunction with the important interface with proteins, nucleic acids, and other biological macromolecules. The historyofsugar chemistryhas come full circle since the grandeur of the EmilFisher era, and the exciting, purely chemical activities of the latter part of the twentieth century. Sugar chemistry has emergedasa pivotal link betweenmolecular recognitionand biological events in conjunction with vital life processes. The preceding preamble to asugar chemistrypanoramawas necessary for me to introduce this timely monograph to the readers. In The Organic Chemistry of Sugars,authors/editors Daniel Levy and Pe ´ter Fu ¨gedi have captured the beauty of thispanorama in acollection of 16 authoritative chapterscovering the essence of almost every aspectofsynthetic sugar chemistry.By focusing on the “organic chemistry” aspectofsugars, the monograph takesthe form of a textbookincertain chapters, providingexcellentcoverageoftraditionaland contemporary methods to manipulate, use, and exploit sugar molecules. With the availability of this monograph, theknowledge base of modern carbohydratechemistry will be considerably richer for the practitionersofthis time-honored and venerablebranchoforganic chemistry. Stephen