Carbohydrates from chiral precursors

Several enzymatic procedures have been developed for the synthesis of carbohydrates from acyclic precursors. Aldolases appear to be useful catalysts for the construction of sugars through asymmeteric C-C bond formation. 2-deoxy-KDO, 2-deoxy-2-fluoro-KDO, 9-0-acetyl sialic acid and several unusual sugars were prepared by a combined chemical and enzymatic approach. Alcohol dehydrogenases and lipases have been used in the preparation of chiral furans, hydroxyaldehydes, and glycerol acetonide which are useful as building blocks in carbohydrate synthesis. 

Stereoselective hydrogenation. A stereoselective synthesis has been reported of the naturally occurring form of a -multistriatin (5), the aggregation pheromone of the European elm beetle, the vector of Dutch elm disease in North America. The synthesis is another example of the value of carbohydrates as chiral precursors to natural products. In this case, the known epoxide 1, derived from D-glucose, was converted in several steps into 2. The crucial next step required hydrogenation to 3 with the 1,3-diaxial configuration of the two methyl groups. The desired selectivity was attained by use of Wilkinson s catalyst. 

A new strategy for the predictable creation of new chiral centres and its application to the synthesis of sugars and macrocycles is presented in a review on the use of double asymmetric induction in the aIdol condensation, the Diels Alder cycloaddition, epoxidation and hydrogenation. Two approaches to the construction of appropriately functionalised six-carbon chains are outlined in a review on the dg novo synthesis of carbohydrates from achiral precursors (i), hetero-Diels Alder reaction with inverse... 

The synthesis of natural products by chirality transfer from carbohydrates has been used for a total synthesis of (-)-(7S)-nonactic acid (199). The furanoid glycal (197) was prepared from D-mannose, which is the appropriate chiral precursor (Scheme 46) (80JOC4259). A [3,3]-sigmatropic rearrangement of the silylated ketene-acetal (198) led to the control of the C-2 configuration. The intermediate furanoid glycal was prepared in ten steps from the carbohydrate precursor. 

The use of chiral precursors involves starting with chiral substrates, usually prepared from amino acids or carbohydrates, with the chirality transferred to the final product. In 1998, Marco-Contelles and co-workers showed that the carbohydrate derived enol ether 26 could be used to give enyne 27, which was then subsequently reacted in an intramolecular PK reaction to afford the tricyclic unit 28 which was central to their target molecule (Scheme 10).38... 

These are (1) The chiral substrate approach. This approach involves using chiral precursors that transfer their chirality to the final cyclopentenone. This implies the synthesis of chiral substrates, which has generally been made from classic chiral pools. Examples include carbohydrate derivatives like 40 that give 41 with variable yields depending on the substitution pattern. 41 is transformed into cyclopenta[c]pyrane 42, which is the skeleton of iri-doids [93]. In another example epichlorhydrin (43) is used to construct chiral enyne 44 which gives cyclopentenone 45 [94] (Scheme 14). 

Reviews have appeared on the synthesis of inositols, carba sugars, conduritols and amino conduritols utilizing the non-carbohydrate sources of benzene cis-diols, quinic acid and Vogel s naked sugar methodology. Other reviews on the preparation of cyclophellitol and ep/-cyclophellitol from glycals and the use of D-glyceraldehyde as a chiral precursor in Diels-Alder and 1,3-dipolar cycloaddition approaches to carbocyclic derivatives have also been reported. 

Carbohydrates have again been used as chiral precursors for the total synthesis of other natural products, including thromboxane Bj, ( —)-isoavenaciolide, and insect pheromones - but pride of place must be given to a total synthesis of (-l-)-biotin from o-glucose in which a biomimetic transformation was used in forming the tetrahydrothiophen ring (Chapter 23). 

The use of carbohydrates in the synthesis of a-aminoacids, covering both situations in which the sugar is used as a chiral precursor, and where it acts as a chiral auxiliary, has been reviewed.73 Reviews have also been published, in Russian, on the stereoselective synthesis of and y-aminoacids and polyoxins,74 and of uncommon aminoacids such as streptothricin components,73 from sugars. 

The regio- and stereo-selective functionalization of aldonolactones yields optically active lactones, which are important precursors in natural product synthesis. Concepts such as chiral templates and chirons, derived from carbohydrates, have been ingeniously and widely applied in synthesis (233). Among the commercially available aldonolactones, D-ribono-1,4-lactone is... 

Casu, F., Chiacchio, M.A., Romeo, R. and Gumina, G., Chiral synthesis of heterosubstituted nucleoside analogs from non-carbohydrate precursors. Curr. Org. Chem., 2007, 11, 1017-1032. 

A variety of cycloheptenols 24 can be synthesized in enantiomerically pure form with high chemical yields by ring-closing metathesis of acyclic, chiral polyoxyge-nated 1,8-nonadiene precursors 23 derived from carbohydrates [Eq. (6.20)]. ... 

Carbohydrates are configurationally stable, easily available in enantiopure forms from the chiral pool, and they show a high density of chiral information per molecular unit. Their polyfunctionality and structural diversity fadhtate their tailor-made modification, derivatization, and structural optimization for a broad spectrum of synthetic applications. While derivatives of various saccharides have already been utilized as versatile starting materials and building blocks for chiral auxiliaries, ligands, and reagents [330] their obvious role as precursors for the... 

From among the variety of non-carbohydrate precursors, acetylenes and alkenes have found wide application as substrates for the synthesis of monosaccharides. Although introduction of more than three chiral centers having the desired, relative stereochemistry into acyclic compounds containing multiple bonds is usually difficult, the availability of such compounds, as well as the choice of methods accessible for their functionalization, make them convenient starting-substances for the synthesis. In this Section is given an outline of all of the synthetic methods that have been utilized for the conversion of acetylenic and olefinic precursors into carbohydrates. Only reactions leading from dialkenes to hexitols are omitted, as they have already been described in this Series.7... 

R. E. Ireland and J. P. Vevert, A chiral total synthesis of (—) and (+) nonactic acids from carbohydrate precursors and the definition of the transition for the enolate Claisen rearrangement in heterocyclic systems, J. Org. Chem. 45 4259 (1980). 

Quite recently, Marco-Contelles [73] has made use of free radical cyclization and ring-closing metathesis in order to develop useful synthetic protocols to access a number of chiral non-racemic, densely oxygenated medium-sized carbocycles from carbohydrate precursors. 

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