Stereochemistry carbohydrates

This chapter is divided into two parts The first and major portion is devoted to carbohydrate structure You will see how the principles of stereochemistry and confer matronal analysis combine to aid our understanding of this complex subject The remain der of the chapter describes chemical reactions of carbohydrates Most of these reactions are simply extensions of what you have already learned concerning alcohols aldehydes ketones and acetals... 

Fischer projections and d-l notation have proved to be so helpful m representing carbohydrate stereochemistry that the chemical and biochemical literature is replete with their use To read that literature you need to be acquainted with these devices as well as the more modern Cahn-Ingold-Prelog R S system... 

Aldoses exist almost exclusively as their cyclic hemiacetals very little of the open chain form is present at equilibrium To understand their structures and chemical reac tions we need to be able to translate Fischer projections of carbohydrates into their cyclic hemiacetal forms Consider first cyclic hemiacetal formation m d erythrose To visualize furanose nng formation more clearly redraw the Fischer projection m a form more suited to cyclization being careful to maintain the stereochemistry at each chirality center... 

Antineoplastic Drugs. Cyclophosphamide (193) produces antineoplastic effects (see Chemotherapeutics, anticancer) via biochemical conversion to a highly reactive phosphoramide mustard (194) it is chiral owing to the tetrahedral phosphoms atom. The therapeutic index of the (3)-(-)-cyclophosphamide [50-18-0] (193) is twice that of the (+)-enantiomer due to increased antitumor activity the enantiomers are equally toxic (139). The effectiveness of the DNA intercalator dmgs adriamycin [57-22-7] (195) and daunomycin [20830-81-3] (196) is affected by changes in stereochemistry within the aglycon portions of these compounds. Inversion of the carbohydrate C-1 stereocenter provides compounds without activity. The carbohydrate C-4 epimer of adriamycin, epimbicin [56420-45-2] is as potent as its parent molecule, but is significandy less toxic (139). 

Many classes of natural product possess heterocyclic components (e.g. alkaloids, carbohydrates). However, their structures are often complex, and although structure-based names derived by using the principles outlined in the foregoing sections can be devised, such names tend to be impossibly cumbersome. Furthermore, the properties of complex natural product structures are often closely bound up with their stereochemistry, and for a molecule containing a number of asymmetric elements the specification of a particular stereoisomer by using the fundamental descriptors (R/S, EjZ) is a job few chemists relish. 

Most parent structures consist essentially of an assembly of rings and/or chains, the degree of hydrogenation of which is defined (usually completely saturated or containing the maximum number of non-cumulative double bonds in cyclic portions), and having no attached functional substituents (the carbohydrates are a notable exception to this). The stereochemistry at all (or most) chiral centres is defined thus such parent structures are sometimes referred to as stereoparents . Some examples are shown (77)-(83). 

Fischer projections and d-l notation are commonly used to describe carbohydrate stereochemistry. The standards are the enantiomers of glycer-aldehyde. 

O-Isopropylidene derivatives of carbohydrates form structural isomers from carbohydrates which themselves are epimers. Since structural isomers often fragment differently whereas epimers do not, mass spectra of these derivatives may permit interpretation in terms of stereochemistry. Although molecular-ion peaks are not observed, the molecular weight can be determined readily from a relatively intense M-CH/ peak, resulting from loss of a methyl radical from a 1, 3-dioxolane ring (12). 

Because carbohydrates usually have numerous chirality centers, it was recognized long ago that a quick method for representing carbohydrate stereochemistry is needed. In 1891, Emil Fischer suggested a method based on the projection of a tetrahedral carbon atom onto a flat surface. These Fischer projections were soon adopted and are now a standard means of representing stereochemistry at chirality centers, particularly in carbohydrate chemistry. 

If substitution at the terminal carbon atom of the carbohydrate chain creates a chiral centre, the stereochemistry is indicated by the R.S system. 

Entry 2 was reported as part of a study of the stereochemistry of addition of allyltrimethylsilane to protected carbohydrates. Use of BF3 as the Lewis acid, as shown, gave the product from an open TS, whereas TiCl4 led to the formation of the alternate stereoisomer through chelation control. Similar results were reported for a protected galactose. 

Entries 6 to 8 demonstrate addition of allyl trimethylsilane to protected carbohydrate acetals. This reaction can be a valuable method for incorporating the chirality of carbohydrates into longer carbon chains. In cases involving cyclic acetals, reactions occur through oxonium ions and the stereochemistry is governed by steric and stereo-electronic effects of the ring. Note that Entry 8 involves the use of trimethylsilyl... 

There have been several syntheses of P-D lactone that were based on carbohydrate-derived starting materials. The starting material used in Scheme 13.42 was prepared from a carbohydrate produced in earlier work.27 The relative stereochemistry at C(4)... 

The synthesis in Scheme 13.44 is also based on a carbohydrate-derived starting material. It controlled the stereochemistry at C(2) by means of the stereoselectivity of the Ireland-Claisen rearrangement in Step A (see Section 6.4.2.3). The ester enolate was formed under conditions in which the T -enolate is expected to predominate. Heating the resulting silyl enol ether gave a 9 1 preference for the expected stereoisomer. The... 

In the carbohydrate chemistry arena, the Tsuji-Trost reaction has been applied to construct N-glycosidic bonds [53]. In the presence of Pd2(dba>3, the reaction of 2,3-unsaturated hexopyranoside 68 and imidazole afforded N-glycopyranoside 69 regiospecifically at the anomeric center with retention of configuration. In terms of the stereochemistry, the oxidative addition of allylic substrate 68 to Pd(0) formed the jc-allyl complex with inversion of configuration, then nucleophilic attack by imidazole proceeded with another inversion of the configuration. Therefore, the overall stereochemical outcome is retention of configuration. 

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