Isopropylidene sugars

P. M. Bhaskar, M. Mathiselvam, and D. Loganathan, Zeolite-catalyzed selective deprotection of di- and tri-O-isopropylidene sugar acetals, Carbohydr. Res., 343 (2008) 1801-1807. 

V. K. Rajput and B. Mukhopadhyay, Sulfuric acid immobilized on silica An effcient reusable catalyst for the synthesis of O-isopropylidene sugar derivatives, Tetrahedron Lett., 47 (2006) 5939-5941. 

The reagent reacts with O-isopropylidene sugars to give chlorofluoroacetates 8 Formation of esters was originally believed to be due to the presence of water, but in the present case esters were still obtained under strictly anhydrous conditions. 

The 1,2-0-isopropylidene sugars have a linkage formed from two acetal hydroxyls, as in sucrose. Hence, it would be expected that the group would be removed easily by acids. It is of interest that the 5,6-0-isopropylidene group is even more easily removed. 

The structures of the 0-isopropylidene sugars have been extensively investigated particularly by application of the methylation procedure 177). 

Fortunately, the oxidation of l,2 5,6-di-0-isopropylidene-a-D-glucofura-nose to l,2 5,6-di-0-isopropylidene-a-D-nfoo-hexofuranos-3-ulose (1) can be accomplished using either phosphorus pentoxide (10, 44) or acetic anhydride (10, 52) in methyl sulfoxide although this oxidation is effected with ruthenium tetroxide (6,7, 46), it is exceeding difficult with other oxidizing agents (53). Keto-sugar 1 is reduced stereospecifically... 

Deoxy-D-jcylo hexose 6-(dihydrogen phosphate) (21) has also been synthesized (2) the reaction sequence makes use of 3-deoxy l 2,5 6-di-O-isopropylidene D-galactofuranose (16), a compound that can be easily prepared from D-glucose (2, 60). The mono-isopropylidene derivative (17) formed by partial hydrolysis of the di-ketal is converted into the 6-tosylate (18) by reaction with one molar equivalent of p-toluenesulfonyl chloride. From this the epoxide (19) is formed by reaction with sodium methoxide. Treatment of the anhydro sugar with an aqueous solution of disodium hydrogen phosphate (26) leads to the 6-phosphate (20)... 

The 3-deoxy 1,2-O-isopropylidene D-gluco- (37) and D-galacto-furanoses (17) have been used (53, 58) in yet another way to prepare deoxy sugars phosphorylated in the terminal position. If either of these compounds is treated with one molar equivalent of periodate, carbon 6... 

The use of tetra-n-butylammonium fluoride (54) in an aprotic solvent such as acetonitrile may be more advantageous. Foster and colleagues (19, 37) have effected an SN2 type of reaction using this reagent in the conversion of l,2 5,6-di-0-isopropylidene-3-0-p-tolylsulfonyl-D-allofura-nose into the C-3 epimeric fluorodeoxy derivative. Note that whereas potassium fluoride is ineffective in displacing secondary sulfonate esters in sugars, tetra-n-butylammonium fluoride is capable of effecting a displacement with Walden inversion even in a furanose drivative. 

The only recorded example using this method in the sugar series is the chlorination of l,2 3,4-di-0-isopropylidene-D-galactopyranose (73) which affords in addition to the expected 6-chloro-6-deoxy derivative 74a, a 5,6-unsaturated derivative 75 as well. These products were separated by silica gel column chromatography no yields were given. 

The synthesis of halodeoxy sugars has also been achieved by reaction of sugar phosphorodiamido and phosphonamido derivatives with alkyl halides (83). Heating equimolar amounts of 6-(tetraethylphosphoro-diamido)-l,2 3,4-di-0 isopropylidene-D-galactose with methyl iodide (and benzyl bromide) at 140°C. for 4 hours afforded the 6-deoxy-6-iodo (74b) (75%) and 6-bromo-6-deoxy (74c) (56%) derivatives, respectively. 

The present work involves the study of methyl glycosides and O-isopropylidene ketals of various isomeric deoxy sugars by mass spectrometry. Several of the compounds selected for the present study have free hydroxyl groups, and interpretation of their mass spectra shows the scope of the study of these and related deoxy sugar derivatives by mass spectrometry without prior substitution of all hydroxyl groups. Some of the candidates (compounds 4, 7, 8 and 10) are structurally related to biologically-derived deoxy sugars. 

Peaks at m/e 113 and 85 have been found in the mass spectra (12) of other O-isopropylidene ketals of sugars, as well as in Figure 7. Since these shift to m/e 119 and to m/e 88 and 91 in the mass spectrum of 10a as they did for the d6-analogs in Reference 12, the structures, 17, 18, and 19 from Reference 12 are shown as possible explanations. The peak at m/e 85 (91) could alternatively be from m/e 113 (119) by loss of carbon monoxide (28 mass units) from the six-membered-ring of structure 17b. 

Pressured cycloaddition of (E)-l-methoxybutadiene (18b) with l 2,3 4-di-0-isopropylidene-a-D-galactopyranos-6-ulose (73) diastereoisomerically afforded pure cycloadduct 74, that exhibits the cis arrangement of the methoxy group with respect to the sugar moiety [27] (Scheme 5.7). Similar results were obtained with the sugar aldehydes 75 and 76. 

The branched-chain sugar fluoromethylphosphonate (573) was pre-pared by treatment of l,2 5,6-di-(7-isopropylidene-a-D-r/7)0-hexofur-anos-3-ulose (572) with lithio(fluoromethyl)diisopropylphosphonate (0x0-lane, — 78° room temp.) to give a diastereoisomeric mixture having the vt-allo configuration. 

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