Branched-chain sugars dithiane

M. Funabashi and J. Yoshimura, Branched chain sugars. Part 14. Synthesis of new branched-chain cyclitols having myo- or scyllo-, and muco-configuration from 3-< -benzyl-5,6-dideoxy-5-C-(l,3-dithian 2-yl)-6-nitro-L-idofuranose and D-glucofuranose, J. Chem. Soc. Perkin Trans, p. 1425 (1979). 

Diels-Alder reaction, 233, 239, 252 dithiane, 214, 216, 219, 242, 244 doubly branched-chain sugars, 235 enolate type anions, 214, 242, 248... 

The value of the 1,3-dithian route to branched-chain sugar derivatives has been illustrated further by stereospecific syntheses of 3-C-formyl, 3-C-hydroxymethyl, and 3-C-methyl derivatives of D-psicose from the ketone (373) via the dithianyl adduct (374). Addition of nitromethane to (373) gave both 3-C-nitromethyl-o-psicose and -fructose derivatives, which, after separation by chromatography, were reduced to the corresponding 3-C-aminomethyl derivatives. The use of dithianyl derivatives in the synthesis of streptomycin components is dealt with in Chapter 18. 

A review lecture including the synthesis of branched-chain sugars using the dithiane route and glycoside synthesis with branched-chain sugars has been published and full reports on the synthesis of the y-octose obtained from isoquinocycline A and of related 4-C-hydroxyethylhexose derivatives have now appeared (see Vol. 10, p. 98). 

Regioselective opening of 2 ,3 -/yxo-epoxides with a lithiated dithian gave rise to branched structures of type (63, B=U or T) which could be converted (Scheme 9) into 3 -C-difluoromethyl compounds (64) and thence into analogues (65) with an additional fluorine atom at C-2 . 22 Alternatively, intermediates (63) could be used as precursors for 3 -C-hydroxymethyl systems (66), 23 and, by successive fluorination, fluoromethyl analogues of types (67) and (68) were obtained. 22 jn a synthesis of 3 -deoxy-3 -hydroxymethyl adenosine (69), the branched-chain sugar derivative (70),... 

Derivatives of unsaturated sugars have been used as starting materials for the synthesis of a number of branched-chain sugars. Pyranosidic enones, for example, were shown to undergo 1,4-additions with lithium dimethyl cuprate, vinyl magnesium bromide, and 2-lithio-2-ethoxycarbonyl-l,3-dithiane, with the carbanion adding trans to the glycosidic substituent (Scheme 66). 4,6-Di-O-... 

As with epoxides, carbanions can add in a 1,4 fashion to enones or nitrosugars. Nitromethane anion has been used [64], Dithiane anion has been successfully used in the addition to nitroolefins [65] and to enones [66], Accordingly, C-5 branched-chain glucose derivatives 47 and 48 have been prepared from nitroolefin 46 (Scheme 20) [67,68], Sugar-derived enones have been also used as acceptors in free radical reactions to trap alkyl radicals as well as anomeric radicals (see Schemes 29 and 30). 

Nitroalkenes, vinyl sulfones and vinylphosphonium salts have been shown as good Michael acceptors for 2-lithio-l,3-dithiane derivatives. Nitroalkene sugar derivative 246 has been used as electrophile for the synthesis of branched-chain cyclitols397 - 399. Seebach and Langer studied the addition to simple nitroalkenes using the chiral solvent (,S ,.S )-DDB (247) with some degree of diastereoselectivity400,401. 

A number of branched chain nitro-cyclitols have been prepared by Michael addition of lithium dithiane to unsaturated nitrosugars followed by cyclization (Scheme 4) conformational effects in the 6-nitro-a/de/iydo-sugar on the stereo-... 

Reaction of the conventional 3-ulose prepared from di-O-isopropyl-idene-D-glucofuranose with nitromethane provided both the alio- and gluco- isomers of the corresponding 3-G-nitromethyl sugars, which were then converted by standard procedures to 3-C-hydroxymethyl pentoses with D-ribo, D-xylo, and D-lyxo configurations the last of these proved to be enantiomeric with the monosaccharide isolated from Phase I Coxiella burnetii LPS, which was confirmed by a synthesis of the L-form (16) from L-arabinose using the 3-ulose (17) with lithio 1, 3-dithiane to introduce the required L-lyxo branch chain. 

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. ... 

Paulsen s group has reported the synthesis of derivatives (256) and (257) of the hydroxyethyl-branched octose that is found as a component of the quinocycline complexes isolated from Streptomyces aureofaciens. The route from the epoxyketone (255) is outlined in Scheme 59. An identical route was used to prepare branched-chain analogues in the o-series, in which it was shown that acid-catalysed methanolysis of the hydroxyethyl-branched derivative (258) yielded the more stable isomer (259) via the anhydro-sugar d-(257). Paulsen s group has also described a synthesis of a derivative (260) of pillarose (see Vol. 9, p. 99), a component of the antibiotic pillaromycin, using the dianion (261) prepared from 2-hydroxymethyl-l,3-dithiane to introduce the branch at C-4 (Scheme 60). A similar approach, using the anion derived from 2-methyl-l,3-dithiane, and subsequent desulphurization and reduction, etc., was adopted in a synthesis of a derivative (262) of aldgarose (4,6-dideoxy-3-C-[(i )-l-hydroxyethyl]-D-W6o-hexopyranose 3,3 -cyclic carbonate) (cf. Vol. 8, p. 100). 

L-Streptose 2-Lilhio-1,3-dithiane has been used in the synthesis of branched sugars with aldehyde or keto groups in the side chain. The reaction sequence is illustrated for the synthesis of L-streptosc (4) from the 3-ulose (1). The most critical step is the... 

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