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The dimethyl acetals of d -glucose, d -xylose, and l -idose were prepared in 15–25% yield by Fischer glycosidation in the presence of strontium or calcium chloride, whereas no dimethyl acetal was isolated in the absence of these cations. Complexing of these dimethyl acetals with cations was indicated by n.m.r. spectra and by electrophoresis. From the reaction of l -idose, the two (previously unknown) methyl l -idofuranosides were isolated.

The crystal and molecular structure of 3-chloro-3-deoxy-1,2;5,6-di-O-isopropylidene-β-D-idose has been determined from three dimensional X-ray data collected by counter methods. The structure was refined by full-matrix least-squares techniques to a conventional R factor of 5.7% for the 817 observed reflections. The compound crystallizes in the orthorhombic space group P212121 with four molecules in a cell of dimensions a = 9.744(6), b = 26.76(2), c = 5.403(3) Å.The structure analysis has served to confirm the site of halogenation and that it occurs stereospecifically. The conformation of the furan ring is an envelope arrangement with C(4) displaced from the mean plane.

The cyclization (internal Henry addition) of 6-deoxy-3-O-methyl-6-nitro-D-glucose (1) and-L-idose (2) was investigated with respect to the sequence in which stereoisomeric deoxynitroinositol methyl ethers are formed from each. It was found that, under conditions of kinetic control, the primary products generated from 1 are the nitronate 4′ (that corresponds to the epimeric deoxynitroinositols 4 and 5 having the epi-3 and muco-3 configurations, respectively) and the nitronate D-6′ of optically active 1-deoxy-4-O-methyl-1-nitro-L-myo-inositol (L-6). They are formed in approximately equal proportions. Ensuing thermodynamically controlled processes lead to racemization of L-6 and formation of the scyllo isomer 3 at a relatively slow rate. The cyclization of 2, found to be faster than that of 1, gave as primary products the enantiomeric nitronate D-6′ and the nitronate 3′ in a ratio of about 4:1. The nitronate 4′ arose by subsequent epimerization. The optically active compounds D-6 and L-6 were isolated in pure, crystalline form.

By hydroboration of enolic hexose derivatives with diborane- 3 H, specific labelling with tritium can be achieved in hexoses. Syntheses of methyl α- d -glucopyranoside-5- 3 H, methyl β- l -idopyranoside-5- 3 H, methyl α- d -mannopyranoside-5- 3 H, methyl β- l -gulopyranoside-5- 3 H, and d -galactose-4- 3 H are described. This method can also be used to change partially easily accessible sugars such as d -glucose, d -mannose, and d -galactose into rare sugars such as l -idose, l -gulose, and l -altrose, respectively, via enolic derivatives of the starting materials. In the case of 3-deoxy-1,2:5,6-di- O -isopropylidene-α- d - erythro -hexofuran-3-enose a complete conversion of d -glucose into d -galactose has been achieved. In all cases, anti-Markownikoff addition of diborane to enolic sugar derivatives was observed. The steric effects of substituents on the addition of diborane to enolic sugar derivatives are discussed.

Treatment of 6-azido-6-deoxy-1,2-O-isopropylidene-3-5-di-O-mesyl-αd-glucofuranose (1) with hydrazine-Raney nickel formed an intermediate 5,6-epimine which immediately underwent reductive ring-opening to yield the salt of methanesulphonic acid and 5-amino-5,6-dideoxy-1,2-O-isopropylidene-3-O-mesyl-β-l-idofuranose (3). N-Acetylation of 3 gave 5-acetamido-5,6-dideoxy-1,2-O-isopropylidene-3-O-mesyl-β-l-idofuranose (4), which was prepared independently by selective substitution of 6-deoxy-1,2-O-isopropylidene-3,5-di-O-mesyl-αd-glucofuranose (6) with azide, reduction, and N-acetylation. Hydrolysis of the sulphonate and isopropylidene groups gave 5-acetamido-5,6-dideoxy-l-idose, as a mixture of the isomeric furanose (9) and piperidinose (10) forms which were separated by column chromatography.

Acetylation of benzyl 6-deoxy-3,4O-isopropylidene-β- L -galactopyranoside gave benzyl 2-O-acetyl-6-deoxy-3,4-O-isopropylidene-β- L -galactopyranoside (1). Removal of the isopropylidene group afforded benzyl 2-O-acetyl-6-deoxy-β- L -galactopyranoside (2), which was converted into benzyl 2-O-acetyl-6-deoxy-3,4-di-O-(methyl-sulfonyl)-β- L -galactopyranoside (3). Benzyl 2,3-anhydro-6-deoxy-4-O-(methyl-sulfonyl)-β- L -gulopyranoside (4) was obtained from 3 by treatment with alkali. Reaction of 4 with sodium azide in N,N-dimethylformamide gave a mixture of two isomeric benzyl 2,4-diazido-2,4,6-trideoxy hexoses, the syrupy diazido derivative 5 and the crystalline benzyl 2,4-diazido-2,4,6-trideoxy-β- L -idopyranoside (6). Acetylation of 6 afforded a compound whose n.m.r. spectrum was completely first order and in agreement with the structure of benzyl 3-O-acetyl-2,4-diazido-2,4,6-trideoxy-β- L -idopyranoside (7). Lithium aluminium hydride reduction of 5, followed by acetylation, afforded a crystalline product (8), shown by n.m.r. spectroscopy to be benzyl 2,4-diacetamido-3-O-acetyl-2,4,6-trideoxy-β- L -altropyranoside. Similar treatment of the diazido derivative 6 afforded benzyl 2,4-diacetamido-3-O-acetyl-2,4,6-trideoxy-β- L -idopyranoside (9). Compounds 8 and 9 could also be obtained from 4 by treatment of the crude diazido mixture with lithium aluminium hydride, with subsequent N-acetylation. The syrupy benzyl 2,4-diacetamido-2,4,6-trideoxy-β- L -altropyranoside (10) and the crystalline benzyl 2,4-diacetamido-2,4,6-trideoxy-β- L -idopyranoside (11) thus obtained were then O-acetylated to give 8 and 9 respectively. Benzyl 2,4-diacetamido-2,4,6-trideoxy-β- L -talopyranoside (15) was obtained from 11 by treatment with methanesulfonyl chloride and subsequent solvolysis. Compound 15 was O-acetylated to yield benzyl 2,4-diacetamido-3-O-acetyl-2,4,6-trideoxy-β- L -talopyranoside (16). the n.m.r. spectrum of which was in full agreement with the assigned structure. The mass spectra of compounds 8–11, 15, and 16 were also in agreement with their proposed structures. Removal of the benzyl groups from 10, 11 and 15 afforded the corresponding 2,4-diacetamido-2,4,6-trideoxyhexoses 12, 13, and 17, having the L -altro, L -ido, and L -talo configurations, respectively.

L-Idose (10) was prepared via its 1,2-O-isopropylidene derivative (9). The latter was prepared by means of the known principle of inverting the configuration of C-5 in sulfonic esters derived from 1,2-O-isopropylidene-α-D-glucofuranose, but a number of new intermediates and variations in procedure were studied in order to achieve practical improvements. Starting compounds were the 3,5-di-p- toluenesulfonate (1), the 3-methanesulfonate-5-p-toluenesulfonate (4), and the 5-p-toluenesulfonate (7) of 6-O-benzoyl-1,2-O-isopropylidene-α-D-glucofuranose, and intermediates were the 3-p-toluene-sulfonate-5-acetate (2), the 3-methanesulfonate-5-acetate (5), and the 3,5-diacetate (8) of 6-O-benzoyl-1,2-O-isopropylidene-β-L-idofuranose. Compound 8 was converted into 9 directly, whereas 2 and 5 gave 9 by sodium reduction of their 5,6-deacylated derivatives 3 and 6.

The base-catalyzed addition of nitromethane to 5-deoxy-D-xylose gave a mixture of 1,6-dideoxy-1-nitro-D -gulitol (2) and 1,6-dideoxy-1-nitro-D-iditol (3) (ca. 1;1) which underwent the Nef reaction to give 6-deoxy-D-gulose and 6-deoxy-D-idose, Acetylation of mixed 2 and 3 afforded the corresponding 2,3,4,5-tetra-O-acetyl-1,6-dideoxy-1-nitro-D-gulitol (4) and 2,3,4,5-tetra-O-acetyl-1,6-dideoxy-1-nitro-D-iditol (5) derivatives which on treatment with methanolic ammonia yielded 2-acetamido-1,2,6-trideoxy-1-nitro-D-gulitol (11) and 2-acetamido-1,2,6-trideoxy-1-nitro-D-iditol (12) (ca. 6:1). Compounds 11 and 12 underwent the modified Nef reaction to give 2-acetamido-2,6-dideoxy-D-gulose (13) and 2-acetamido-2,6-dideoxy-D-idose (14) which were separated by cellulose column chromatography.Compound 4 was converted to 3,4,5-tri-O-acetyl-1,2,6-trideoxy-1-nitro-D-xylo-hex-1-enitol (6) which on catalytic reduction gave 3,4,5-tri-O-acetyl-1,2,6-trideoxy-1-nitro-D-xylo-hexitol (7). Compound 7 underwent the Nef reaction to yield 2,6-dideoxy-D-xylo-hexose (8) (D-boivinose).

There has been a substantial increase in recent years in the number of fluorinated carbohydrates. One of the reasons for interest in these sugars is that the introduction of a fluorine atom into naturally occurring compounds involved in biochemical processes has, in several instances, produced analogues having significant biological activity and, in some icstances, of therapeutic value’. The most successful ways for specifically introducing a fluorine atom into sugars have used’ (a) nucleophilic displacement of sulphonates with fluoride ion, (6) opening of epoxides, and (c) electrophilic addition of trifluoro(fluoroxy)methane to glycals. Other methods have been applied with less success3. The foregoing procedures have made a number of fluoro sugar derivatives available in quantities sufficient for further transformations to be effected, thereby providing routes to other, less-accessible compounds. Such procedures have been used already in the synthesis of difluoro sugars4, and 3-deoxy-3-fluoro-D-xylose has been prepared5 by a sequence of reactions based on 3-deoxy-3-fluoro-1,2:5,6-di-Oisopropylidene-cc-D-glucofuranose. We now report the conversion of the latter compound into derivatives of 3-deoxy-3-fluoro-L-idose. 3-Deoxy-3-fluoro-1,2:5,6-di-Oisopropylidene-P-L-idofuranose (2) was previously obtained6 by the reaction of tetra-n-butylammonium fluoride in boiling acetonitrile with 1,2:5,6-di-O-isopropylidene-3-0-toluene-p-sulphonyl-/3-L-talofuranose (l), but the route to related derivatives described below is far more convenient.

The following chlorodeoxy derivatives have been prepared in high yield by treatment of fully protected isopropylidene acetals of sugars with triphenylphosphine in carbon tetrachloride; 1-chloro-1-deoxy-2,3;4,6-di- O -isopropylidene- L -sorbose ( 1 ), 1-chloro-1-deoxy-2,3;4,5-di- O -isopropylidene- D -fructose ( 2 ), 3-chloro-3-deoxy-1,2;-5,6-di- O -isopropylidene-α- D -glucose ( 3 ) and -β- D -idose ( 4 ), and 6-chloro-6-deoxy-1,2;-3,5-di- O -isopropylidene-α- D -glucose ( 5 ). With the exception of the sorbose derivative, all of the derivatives were converted into their deoxy analogues by treatment with lithium aluminum hydride. Thus, these procedures allow preparation of 3-deoxy- D - ribo -hexose ( 6 ) and 3-deoxy- D - lyxo -hexose ( 7 ) and other deoxy sugars in good yield.

Solvolysis of 1,2- O -isopropylidene-5,6-di- O-p -tolylsulfonyl-α- D -glucofuranose( 9 ) or its 3-benzyl ether ( 1 ) in moist methanolic hydrogen chloride gives 2,5-anhydro-6- O-p -tolylsulfonyl- L -idose dimethyl acetal ( 11 ) and its 3-benzyl ether ( 3 ) in excellent yield. These compounds offer, among other uses, a convenient access to an asymmetric monosulfonate of 2,5-anhydro- L -iditol. The mechanism of the solvolysis reaction is discussed.

The synthesis of the title compound could be achieved by inversion of C-5 in a suitably substituted derivative of 2,6-diamino-2,6-dideoxy- d -glucose (V). Purification of the product by preparative thin layer chromatography and its apparent conformational instability are being emphasized. Its identity with natural paromose has been established.

Versuche zur Darstellung des 6-Amino-6-desoxy-L-idopyranose-hydrochlorids (11) aus 5 zeigten, das dieser Zucker auch in kristallinem Zustand instabil ist und nicht rein isoliert werden kann. Die freie Base cyclisiert sofort unter Bildung der 1.6-Iminoverbindung 8. Ein neuer Syntheseversuch konnte nicht uber das Oxazolin 20, hinausgefuhrt werden.

The addition of nitromethane to aldoses giving 1-deoxy-1-nitroalditols (the Fischer–Sowden reaction) was extended to L-idose. Both epimeric products, 1-deoxy-1-nitro-L-glycero-D-ido-heptitol (1) and 1-deoxy-1-nitro-L-glycero-D-gulo-heptitol (2), were isolated in crystalline form, and 2 was shown to preponderate. The stereoselectivity is evaluated by a comparison of literature data on the Fischer–Sowden reaction of other hexoses, and attention is drawn to the importance of the C-3 configuration in the hexose, which appears to be the main factor influencing the ratio of epimers produced. An explanation in conformational terms is offered.

Mild treatment of 3-deoxy-3-fluoro-1,2- O -isopropylidene-β- L -idofuranose with acid gave 3-deoxy-3-fluoro- L -idose ( 2–3 ) as a syrup. Under more vigorous acid conditions, 2–3 was converted into crystalline 1,6-anhydro-3-deoxy-3-fluoro-β- L -idopyranose, the structure of which was confirmed by the n.m.r. data on the 2,4-diacetate. A solution of 3-deoxy-3-fluoro- L -idose in H 2 O or D 2 O at equilibrium showed four 19 F resonances, which were assigned to the α and β-pyranose and furanose forms, and the proportions of which correspond closely to those observed for D -idose. From the F-H splittings of the appropriate 19 F resonances, the conformation of each pyranose form was deduced.

The p.m.r. spectra of commercial heparin samples from a variety of sources indicate that there are at least two types of heparin. These types are differentiated by small, but distinct, variations in the relative intensities of their proton signals and, most noticeably, by the presence of acetyl groups in samples of one of the types. The spectral data also indicate that approximately equimolar proportions of three kinds of constituent sugar residues are present in all of the heparin samples. Deaminative degradation of a heparin, followed by exhaustive reduction of the carboxyl groups, acetolysis, and deacetylation, yielded L -idose as a major product. It is tentatively concluded that L -idosyluronic acid residues constitute about one-third of the constituent sugars of the commercial heparins, and that the aminodeoxy- D -hexosyl and D -glucosyluronic residues (already recognized as constituents) each constitute one-third of the polymeric material.

The net charges on various atoms of aldohexopyranose pentaacetates were computed by using the MO-LCAO method of Del Re for σ-charges and the Huckel MO method for π-charges. The potential and free energies of sixteen aldohexopyranose pentaacetates in the C1( D ) and 1C( D ) conformations were estimated. Minimization of the energies of these conformations was studied by suitably tilting the axial CC and CO bonds. As with the free sugars, considerable release of strain is achieved when tilts of 4.5 and 2° are given to the axial CH2OAc and the axial OAc groups, respectively, involved in the Hassel—Ottar effect in the 1C( D ) conformations. In the case of C1( D ) conformations, the ideal models have the minimum energy even when the acetate groups are involved in syn-axial interactions, indicating that strain induced by axial acetate groups is less than that of axial hydroxyl groups. The calculated free-energies agree well with the experimental values after adding a value of 0.9 kcal.mole-1 for the anomeric effect of the acetoxyl group. The free-energy calculations also predict that α- D -idohexopyranose pentaacetate and α- D -altrose pentaacetate favour the C1( D ) conformation and β- D -idose pentaacetate a C1⇄1C equilibrium in solution, in agreement with n.m.r. studies.

3,4,5,6-Tetraacetoxy-D-xylo-1-nitro-1-hexene with methanolic ammonia afforded a mixture of 2-acetamido-1,2-dideoxy-1-nitro-D-gulitol and 2-acetamido-1,2-dideoxy-1-nitro-D-iditol which were converted via a Nef reaction to 2-acetamido-2-deoxy-D-gulose and 2-acetamido-2-deoxy-D-idose.Reduction of 3,4,5,6-tetraacetoxy-D-xylo-1-nitro-1-hexene afforded 3,4,5,6-tetra-O-acetyl-1,2-dideoxy-1-nitro-D-xylo-hexitol which was converted via the Nef reaction to 2-deoxy-D-xylo-hexose.

The base-catalyzed addition of nitromethane to 5-deoxy-D-xylose gave a mixture of 1,6-dideoxy-1-nitro-D -gulitol (2) and 1,6-dideoxy-1-nitro-D-iditol (3) (ca. 1;1) which underwent the Nef reaction ...

Publisher Summary This chapter focuses on acetoxonium ion rearrangements. The acetoxonium ion is an ambident cation, which can react with anions in two ways. The acetoxonium ion can quickly and reversibly rearranges into acetoxonium ion under neighboring group participation. At elevated temperatures, rearrangement is fast in terms of the NMR timescale as coalescence of acetoxonium methyl and acetyl methyl signals is observed. Continuous fast cyclorearrangement of acetoxonium ions is found in the acetoxonium salt of pentahydroxycyclopentane. Corresponding rearrangement reactions take place at free acetoxonium ions of monosaccharides. They may be used for preparing new sugars if the rearrangement product can easily be isolated. In this manner, d -idose can be obtained from d -glucose.

The mild acid hydrolysis of 1,2-O-isopropylidene-5,6-anhydro-α- d -glucofuranose has been found to yield, in addition to d -glucose, the new anhydro sugar, 2,5-anhydro- l -idose. The identification of this substance has been described and its properties have been compared with those of some other anhydro sugars.

Galactose, talose, gulose and idose labeled in carbon 2 with 14C were synthesized. The conversion of [14C]galactose to glucose isolated from liver glycogen was investigated in the fasted rat. It was found that the bulk of the isotope was in carbon 2 of glucose, indicating that an inositol intermediate could not be involved in the interconversion.

Methyl 2,3,4,6-tetra-amino-2,3,4,6-tetradeoxy-α-D-galactopyranoside has been synthesised from a 2-acetamido-2-deoxy-allopyranoside by the stepwise introduction of azide groups into the molecule by the nucleophilic displacement of sulphonyloxy-groups. These displacement reactions are greatly facilitated by the use of hexamethylphosphoric triamide as reaction solvent, which is superior to NN-dimethylformamide for this purpose because the reactions can be carried out at a lower temperature at which little or no decomposition of the sulphonate ester occurs. The corresponding idopyranoside has been prepared in a similar fashion from methyl 3-acetamido-2-azido-4,6-O-benzylidene-2,3-dideoxy-α-D-altropyranoside. Steric and electronic factors affecting the displacement reactions of sulphonate esters are discussed.