Furan synthesis from carbohydrates

Neely, W. Brock, Dextran Structure and Synthesis, 16, 341-369 Neely, W. Brock, Infrared Spectra of Carbohydrates, 12, 13-33 Neubehg, Carl, Biochemical Reductions at the Expense of Sugars, 4, 75-117 Neufeld, Elizabeth F., and Hassid, W. Z., Biosynthesis of Saccharides from Glycopyranosyl Esters of Nucleotides ( Sugar Nucleotides ), 18, 309-356 Newth, F. H., The Formation of Furan Compounds from Hexoses, 6, 83-106 Newth, F. H. See also, Haynes, L. J. Nickerson, R. F., The Relative Crystallinity of Celluloses, 6, 103-106 Nord, F. F., [Obituary of] Carl Neuberg, 13, 1-7... 

Carbohydrates have been used as chirons to generate a number of interesting furan derivatives from industrial commodities such as 2-furaldehyde, to more complex, biologically significant compounds with therapeutic potential. Several interesting examples of the use of carbohydrates as starting materials for the synthesis of furans are highlighted below. 

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. 

The popular approach to tetrahydrofurans involves an electrophilic process and the commonly used electrophiles for the cyclization are acids, oxygen, halogen, mercury (see Section 3.11.2.2.9) and selenium. The ionic hydrogenation of furans with excess triethyl-silane in trifluoroacetic acid affords high yields, e.g. 2-methylfuran is reduced to 2-methyl-tetrahydrofuran and 2-ethylfuran to 2-ethyltetrahydrofuran (see Section 3.11.2.5). The synthesis of several dihydro and tetrahydrofurans containing natural products by chirality transfer from carbohydrates has been used successfully for total synthesis, e.g. (-)-nonactic acid. A reasonable yield of 2-alkyltetrahydrofuran was prepared from 4-alkylbut-l-en-4-ol by hydroboration followed by cyclization with p-toluenesulfonic acid. 

C. Fayet and J. Gelas, Synthesis of 3-substituted furans from 3-C-substituted hexuloses, Carbohydr. Res., 155 (1986) 99-106. 

Some other natural compounds have been transformed for their use in the synthesis of polymers via olefin metathesis processes. As mentioned in the introduction, furans, which are obtained from carbohydrates, are perfect precursors of monomers for ROMP via simple Diels-Alder cycloadditions (n) (Scheme 25) [26]. In this regard, the first example of the ROMP of 7-oxabicyclo[2.2.1]hept-5-ene derivatives was reported by Novak and Grubbs in 1988 using ruthenium- and osmium-based catalysts [186]. The number of examples of ROMP with monomers with this generic structure is vast, and it is out of the scope of this chapter to cover all of them. However, it is worth mentioning here the great potential of a renewable platform chemical like furan (and derived compounds), which gives access to such a variety of monomers. 

Considerable work was done to induce chirality via chiral auxiliaries. Reac tions with aromatic a-ketoesters like phenylglyoxylates 21 and electron-rich al kenes like dioxoles 22 and furan 23 were particularly efficient (Scheme 6). Yield up to 99% and diastereoselectivities higher than 96% have been observed whet 8-phenylmenthol 21a or 2-r-butylcyclohexanol 21b were used as chiral auxiliarie [14-18]. It should be noted that only the exoisomers 24 and 25 were obtained from the reaction of dioxoles 22. Furthermore, the reaction with furan 23 wa regioselective. 24 were suitable intermediates in the synthesis of rare carbohydrate derivatives like branched chain sugars [16], Other heterocyclic compounds liki oxazole 28 [19] and imidazole 29 [20] derivatives as well as acyclic alkenes 3fl 31, and 32 [14,15,21,22] were used as olefinic partners. Numerous cyclohexane derived alcohols [18,21-24] and carbohydrate derivatives [25] were used as chiri... 

De Novo Synthesis in Carbohydrate Chemistry From Furans to Monosaccharides and Oligosaccharides... 

The presented review describes total syntheses directed towards 6-amino-6,8-dideoxy-D-eryt/iro-D-galacto-octose, commonly named lincosamine - the sugar component of the antibiotic lincomycin. In the first part we present total syntheses of lincosamine that start from carbohydrate precursors. The D-galactose-derived aldehyde is the most frequently used synthon. In the second part, total syntheses of lincosamine from non-carbohydrate precursors are presented. This part of the review is divided into two subsections. The first one groups syntheses based on the application of furan compounds. In the second one we present a hetero-Diels-Alder approach to the synthesis of lincosamine. 

An important aspect of this approach is the ease with which fiiran alcohols can be prepared in enantiomerically pure form from achiral furans (e.g., 7 and 8). There are many asymmetric approaches to prepare furan alcohols. The two most prevalent approaches are (i) the Noyori reduction ofacylfurans (8 to 12) and (ii) the Sharpless dihydroxylation of vinyUurans (7 to 12) (Scheme 1.4) [17]. Both routes are readily adapted to 100 g scale synthesis and use readily available reagents. While the Sharpless route is most amenable to the synthesis of hexoses with a C-6 hydroxy group, the Noyori route distinguishes itself in its flexibility to virtually any substitution at the C-6 position. Herein, we review the development of the Achmatowicz approach to the de novo synthesis of carbohydrates, with apphcation to oligosaccharide assembly and medicinal chemistry studies. 

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