Chain-extended Sugars

3 Chain-extended Sugars. - 1.3.1 Chain-extension at the Non-reducing End . Methyl 2,3,4-tri-0-benzyl-D-erythro-a-D- /Mco-oct-l,5-pyranoside and its h-erythro- -D-gluco-isomer have been S3mthesized for the first time by cis- hy-droxylation of the appropriate 6-C-vinyl-D- and -i.-glycero-D-gluco-pyra.nose derivatives, respectively.  

Homologation of protected dialdohexoses 23 with a-D-gluco-, a-D-galacto-and a-D-allo-configurations by use of various (substituted-methyl)magnesium chlorides, has been undertaken. Good L-selectivity was achieved with 

PhMe2SiCH2MgCl e.g. 23- 24). The gf/ cero-D-manno-heptopyranoside-7-phosphate analogues 25 were obtained from a dialdehydo-mannopyranoside precursor by reaction with MePO(OEt)2-n-BuLi, followed by deprotection.  

3-0-Benzyl-6-deoxy-l,2-0-isopropylidene-a-D-xy/o-hexofuranos-5-ulose (37) on treatment with carbon disulfide and methyl iodide under basic conditions afforded a-oxoketene dithioacetal 38, which was transformed to pyrazole derivative 39 by exposure to hydrazine hydrate. A 3-deoxy-3,4-unsaturated analogue was similarly prepared. Conversion of ketone 37 to the Knoevenagel product 40 prior to treatment with CS2-MeI-NaH led to the formation of the sugar push-pull-butadiene 41.  

In the presence of chloramine T, the non-reducing end oxime 42 underwent 1,3-polar cycloadditions with terminal alkynes to give 3-glycosyI-5-substituted isoxazoles 43 in moderate yields. Reductive alkylation of pyrroline derivative 44 with methyl 2,3,4-tri-0-benzyl-6-deoxy-6-iodo-a-D-glucopyranoside gave, after ester reduction, osmylation and acetylation-deacetylation, the novel poly-hydroxypyrrolidine 45, containing a methyl glucoside moiety.  

3 Chain-extended Sugars - The application of indium- and tin-mediated Barbier-Grignard reactions in aqueous solutions to the chain-extension of 

Reagents i, Dhap, rabbit muscle aldolase II, phosphatase 

Chain-extension at the Non-reducing End - Both epimers of 6-C-phenylglucose 28 have been synthesized from D-glucuronolactone via intermediates TiP Introduction of a cyclopentadiene moiety at C-6 of diacetonegalactose was effected by reaction of triflate 29 with cyclopentadienyl lithium in DMF to give 30.  

Three papers describing chain-extensions by use of C-6-aldehydes have been published the diacetonegalactose-derived dialdose 31 was extended by two carbons to give the acetamido-dideoxy-octosulose derivative 33 via intermediate 32 by consecutive treatment with potassium cyanide in the presence of ammonia, 

2 Chain-extension at the Reducing End - Catalytic osmylation of the d-fructose-derived ( )- and (Z)-alkenes 39 gave, after reduction with LAH, a mixture of u-glycero-n-galacto- (40) and D-g/ycero-D-/ fo-oct-4-ulose (41), and d- 

Reagents i, FeCp(CO)PPh3Ac, BuLi ii, SnCIa Hi, NBS iv, DIBAL v, aq. HOAc vi, AcaO, Py 

Addition of alkylmanganese reagents, prepared in situ from the corresponding alkyl lithium compoimds and Mnia in ether, to substrates 24 and T1 proceeded diastereoselectively to give 4,5- and 5,6-threo products, respectively. Spiroketals 

2 Chain-extensUm at the Reducing End. - Two-carbon Wittig elongation of 3,4 5,6-di-0-isopropylidene-aldehydo-D-glucose gave adduct 45, which on Mitsunobu inveraon at C-4, hydrogenation of the double bond and lactonization furnished the 4,S-dideoxy-D-mamto-oct-l,4-lactone derivative 46, a synthetic KDO precursor. Anomeric spiroketals have been constructed by alkoxy radical 

Reagents i, AIITms, BF3 Et20 ii, BH3, then H2O2,0H iii, (diacetoxyiodo)benzene, I2, C6H12. hv 

Reagents i, BocN I ii, KMn04 iii, LiOH iv, Nal04 v, NaClOa vi, CH2CI2 

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H. Paulsen, M. Brieden, and V. Sinnwell, Branched and chain-extended sugars, XXVIII. Synthesis of 6-amino-6-deoxyhepturonic acids, Liebigs Ann. Chem., (1985) 113-128. 

The reaction of enolates with lactones has also been carried out to give chain-extended sugars. Three approaches have been published, two on samarium diiodide mediated chemistry [115,116] and one on classical Claisen-type chemistry [117]. Representative examples are shown in Scheme 70. 

A synthesis of (2S)-2-hydroxycastanospermine (280) and (2S)-2-hydroxy-6-e/Ji-castanospermine (277) starts with chain extended sugar 275. 

Spiro- and 1,2-fused Bicyclic Systems. Spiroketals involving C-glycosidic structures can more correctly be considered to be chain-extended sugars (Chapter 2, Section 2.3). Sharpless asymmetric dihydroxylation of 5-aryl-2-vinylfuran... 

The use of 4,5-dihydro-2-lithio-5-methyl-l, 3,5-dithiazine rather than 2-lithio-1,3-dithians for the synthesis of branched-chain and chain-extended sugars is reported to give better results. The dithiazine is more reactive and the products more readily desulphurized. The reagent reacted with primary halides, epoxides, and keto-compounds, but secondary halides underwent elimination. ... 

In the area of pyranoid glycals. Scheme 2 iUustratea the use of D-fiuctose as precursor to glycal 2, a useful intermediate in the preparation of chain-extended sugars/... 

While the evolved format of these Reports largely allows for the handling of new material, some adaptation is desirable and (after some debate) treatment of chain-extended sugar derivatives is now included in Chapter 2. Carbohydrates as chiral auxiliaries is another aspect that the normal format does not accommodate too readily it is treated in Chapter 24, and Chapter 4 now includes brief reference to chemical aspects of the cyclodextrins. 

Unsaturated Sugars. - The enopyranuronates (17) and (18),2,3-dideoxy-a-D-eo fAw-hex-2-enopyranosyl benzene, a 4 1 mixture of 6-amino-6-iV-/ Tf-but03 carbonyl-2,3,6,7-tetradeoxy-QrViL-erythro - and /9-DL-r/ireo-hept-2-enopyranos-4-uloses, and the chain extended sugar alkene (19). ... 

Sugar fermentation and ther- Propylene glycol SolvenL chain extender in... 

Deloisy, S, Kunz, H, A novel synthesis of chain-extended amino sugar derivatives through Aza-Cope rearrangement of A-galactosyl-A-homoallylamines, Tetrahedron Lett., 39, 791-794, 1998. 

Urge, L, Jackson, D C, Gorbics, L, Wroblewski, K, Graczyk, G, Otvos, L Jr, S3mthesis and conformational analysis of V-glycopeptides that contain extended sugar chains. Tetrahedron, 50, 2373-2390, 1994. 

Dihydroxylation of chain-extended unsaturated carbohydrates gives rise to higher sugars. Unsaturated ester 46 is available from glucose by a Wittig reaction in dioxane (O Scheme 16) [133]. Dihydroxylation of 46 affords a 5 1 mixture of two diastereomers and the major isomer is isolated by crystallization as the octonolactone 47 [134]. Interestingly, the two-step procedure can be converted into a one-pot transformation in dioxane by performing the... 

A-Glycosyl homoallylamines have been shown to undergo a stereocontrolled Lewis acid-catalyzed aza-Cope rearrangement to produce chain-extended amino sugars. The reactions proceed in good to excellent yields with high stereoselectivity. Schiff base... 

The Kolbe electrolysis of sugar acids to give radicals and their subsequent trapping with a radical source gave the chain-extended C-glycoside 27 as the major product (Scheme 7). Compounds such as 27 are useful as stable nonionic tensides and are expected to show liquid crystalline properties [11]. 

Heavy metal uptake is primarily based on the ability of microbial surfaces to complex with metal cations. The negatively charged sugar units of polysaccharide chains, extending from the microbial cell wall, may complex with metal cations. 

The application of indium- and tin-mediated Barbier-Grignard reactions in aqueous solution to the chain extension of unprotected sugars has been reviewed. Some C-5 variants of iV-acetylneuraminic acid have been prepared by the indium-mediated addition of ethyl oc-(bromomethyl)acrylate to variously N-substituted mannosamines," and similar chemistry using (bromomethyl)vinyl phosphonate has led to the phosphonate analogue 12. The reaction of O-protected aldono-1,4- and -1,5-lactones with (2-bromomethyl)-acrylate or -acrylonitrile or 2-bromobutyrolactone mediated by samarium diodide led to chain-extended ulosonic acid derivatives." ... 

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