Synthesis of daunosamine-containing disaccharides

Treatment of 2,3,6-trideoxy-1,4-di-O-(p-nitrobenzoyl)-3-(trifluoroacetamido)-l-lyxo-hexopyranose (1) with benzyl 2,3-dideoxy-d-glycero-pentopyranoside and p-toluenesulfonic acid gave a mixture of benzyl 2,3,6-trideoxy-4-O-p-nitrobenzoyl-3- (trifluoroacetamido)-l-lyxo-hexopyranoside (49%) and benzyl 2,3-dideoxy-4-O-[2,3,6-trideoxy-4-O-(p-nitrobenzoyl)-3-(trifluoroacetamido)-α-l-lyxo-hexopyranosyl]-d-glycero-pentopyranoside (4, 20 %). The structure of the disaccharide 4 was confirmed by a detailed, mass-spectrometric analysis in three modes, namely, negative- and positive-ion, chemical ionization, and electron impact. Similar treatment of the bis(p-nitrobenzoate) 1 with ethyl 2,3-dideoxy-d-glycero-pentopyranoside gave the ethyl glycoside and the desired disaccharide, showing that the transglycosylation is not restricted to benzyl glycosides. Removal of the p-nitrobenzoyl and the benzyl groups from 4 gave the disaccharide 2,3-dideoxy-4-O-(2,3,6-trideoxy-3-trifluoroacetamido-α-l-lyxo-hexopyranosyl)-d-glycero-pentopyranose.     

Syntheses of methyl 2,6-diacetamido-2,3,6-trideoxy-α-d-ribo-hexopyranoside (methyl di-N-acetyl-α-d-tobrosaminide) and methyl 2-acetamido-2,3,6-trideoxy-β-l-lyxo-hexopyranoside

The title glycosides were synthesised from d-glucose, via the common intermediate methyl 2-acetamido-4-O-benzoyl-6-bromo-2,3,6-trideoxy-α-d-ribo-hexopyranoside.     

An approach to branched-chain amino sugars,particularly derivatives of l-vancosamine (3-amino-2,3,6-trideoxy-3-C-methyl-l-lyxo-hexose) and its d enantiomer,via the cyanohydrin route

Methyl 4,6-O-benzylidene-2-deoxy-α-d-erythro-hexopyranosid-3-ulose reacted with potassium cyanide under equilibrating conditions to give, initially, methyl 4,6-O-benzylidene-3-C-cyano-2-deoxy-α-d-ribo-hexopyranoside (7), which, because it reverted slowly to the thermodynamically stable d-arabino isomer, could be crystallised directly from the reaction mixture. The mesylate derived from the kinetic product 7 could be converted by published procedures into methyl 3-acetamido-2,3,6-trideoxy-3-C-methyl-α-d-arabino-hexopyranoside, which was transformed into methyl N-acetyl-α-d-vancosaminide on inversion of the configuration at C-4. A related approach employing methyl 2,6-dideoxy-4-O-methoxymethyl-α-l-erythro-hexopyranosid-3-ulose gave the kinetic cyanohydrin and thence, via the spiro-aziridine 27, methyl 3-acetamido-2,3,6-trideoxy-3-C-methyl-α-l-arabino-hexopyranoside, a known precursor of methyl N-acetyl-α-l-vancosaminide.     

Synthesis of D-ristosamine and its derivatives

A convenient preparative route involving eleven steps starting from D-glucose is described for the synthesis of D-ristosamine (15) hydrochloride. Methyl 2-deoxy-β-D-arabino-hexopyranoside, prepared from 3,4,6-tri-O-acetyl-1,5-anhydro-2-deoxy-D-arabino-hex- 1-enitol, was benzylidenated, and the product mesylated to give methyl 4,6-O-benzylidene-2-deoxy-3-O-methylsulfonyl-β-D-arabino-hexopyranoside. Azidolysis of this compound and subsequent opening of the 1,3-dioxane ring with N-bromosuccinimide gave methyl 3-azido-4-O-benzoyl-6-bromo-2,3,6-trideoxy-βD-ribo-hexopyranoside. Simultaneous reduction of the azido and bromo groups gave a mixture that was benzoylated to give methyl N,O-dibenzoyl-β-D-ristosaminide and then hydrolyzed to 15 hydrochloride (3-amino-2,3,6-trideoxy-D-ribo-hexopyranose hydrochloride).     

Synthesis of 5-deoxy-d-xylo-hexose and 5-deoxy-l-arabino-hexose,and their conversion into adenine nucleosides

Anti-Markovnikov hydration of the olefinic bond of 5,6-dideoxy-1,2-O-isopropylidene-3-O-p-tolylsulfonyl-α- d-xylo-hex-5-enofuranose (4) and methyl 5,6-dideoxy-2,3-di-O-p-tolylsulfonyl-α-l-arabino-hex-5-enofuranoside (11) by the addition of iodine trifluoroacetate, followed by hydrogenation in the presence of a Raney nickel catalyst in ethanol containing triethylamine, afforded 5-deoxy-1,2-O-ísopropylidene-3-O-p-tolylsulfonyl-α-d-xylo-hexofuranose (6) and methyl 5-deoxy-2,3-di-O-p-tolylsulfonyl-α-d-arabino-hexofuranoside (14), respectively. 5-deoxy-d-xylo-hexose and 5-deoxy-l-arabino-hexose were prepared from 6 and 14, respectively, by photolytic O-detosylation and acid hydrolysis. Syntheses of 9-(5-deoxy-β-d-xylo-hexofuranosyl)-adenine and 9-(5-deoxy-α-l-arabino-hexofuranosyl)adenine are also described. Application of the sodium naphthalene procedure, for O-detosylation, to 11 is reported in connection with an alternative synthetic route to methyl 5-deoxy-α-l-arabino- hexofuranoside.     

Synthesis of new branched-chain aminodeoxyhexoses related to daunosamine (3-amino-2,3,6-trideoxy-l-lyxo-hexose)

Addition of methylmagnesium iodide to methyl 2,3,6-trideoxy-3-trifluoro-acetamido-α-l-threo-hexopyranosid-4-ulose (3) gave methyl 2,3,6-trideoxy-4-C-methyl-3-trifluoroacetamido-α-l-lyxo-hexopyranoside (4) and its l-arabino analogue, depending upon the reaction temperature and the solvent. The corresponding 4-O-methyl derivatives were obtained by treatment of 4 and 5 with diazomethane in the presence of boron trifluoride etherate. Treatment of 4 with thionyl chloride, followed by an alkaline work-up, gave methyl, 2,3,4,6-tetradeoxy-4-C-methylene-3-trifluoro-acetamido-α-l-threo-hexopyranoside (8), which was stereoselectively reduced to methyl 2,3,4,6-tetradeoxy-4-C-methyl-3-trifluoroacetamido-α-l-arabino-hexopyranoside. Epoxidation of 8 with 3-chloroperoxybenzoic acid gave the corresponding 4,4₁-anhydro-4-C-hydroxymethyl-l-lyxo derivative (10), which was also prepared by treatment of 3 with diazomethane. Azidolysis of 10, followed by catalytic hydrogenation and N-trifluoroacetylation, gave methyl 2,3,6-trideoxy-3-trifuloroacetamido-4-C-trifluoroacetamidomethyl-α-l-lyxo-hexopyranoside.     

Synthesis of 3-amino-2,3,6-trideoxy-ll-lyxo-hexose (daunosamine) hydrochloride from d-glucose

Three different approaches starting from 1,2-O-isopropylidene-α-d-glucofuranose were tested for the synthesis of daunosamine hydrochloride (24), the sugar constituent of the antitumor antibiotics daunomycin and adriamycin. The third route, affording 24 in ~5% overall yield in 11 steps, constitutes a useful, preparative synthesis, 3,5,6-Tri-O-benzoyl-1,2-O-isopropylidene-α-d-glucofuranose was converted via methyl 2,3-anhydro-β-d-mannofuranoside into methyl 2,3:5,6-dianhydro-α-l-gulofuranoside, the terminal oxirane ring of which was split selectively on reduction with borohydride, to afford methyl 2,3-anhydro-6-deoxy-α-l-gulofuranoside (31). Compound 31 was converted into methyl 2,3-anhydro-5-O-benzyl-6-deoxy-α-l-gulofuranoside, which was selectively reduced at C-2 on treatment with lithium aluminum hydride, affording methyl 5-O-benzyl-2,6-dideoxy-α-l-xylo-hexofuranoside. Subsequent mesylation, and replacement of the mesoloxy group by azide, with inversion, afforded methyl 3-azido-5-O-benzyl-2,6-dideoxy-α-l-lyxo-hexofuranoside, which could be converted into either 24 or methyl 3-acetamido-5-O-acetyl-2,3,6-trideoxy-α-l-lyxo-hexofuranoside, which can be used as a starting material for the synthesis of daunomycin analogs.     

Synthesis of crystalline derivatives of 6-deoxy-d-allo- and -l-talo-furanosyl bromide suitable for nucleoside synthesis

6-Deoxy-2,3,5-tri-O-(p-nitrobenzoyl)-β-d-allo- and -α-l-talo-furanosyl bromide (6 and 11) have been synthesized from methyl 2,3-O-isopropylidene-β-d-ribo-pentodialdo-1,4-furanoside (1). Treatment of 1 with methyl Grignard reagent, followed by (p-nitrobenzoyl)ation, afforded two 5-epimers, methyl 6-deoxy-2,3-O-isopropylidene-5-O-(p-nitrobenzoyl)-β-d-allo- and -α-l-talo-furanosides (3 and 8) which were fractionally recrystallized. The l-talo isomer (8) separated first, and was treated with acid to remove the isopropylidene group, the product (p-nitrobenzoyl)ated, and the ester reacted with hydrogen bromide in acetic acid, to afford crystalline compound 11. The mother liquor from the fractional recrystallization was treated with acid, whereby methyl 6-deoxy-5-O-p-nitrobenzoyl)-d-allofuranoside was isolated. It was (p-nitrobenzoyl)ated, and the ester treated with hydrogen bromide in acetic acid, to afford crystalline bromide 6.     

The synthesis and cytotoxic activity of 1,3,4-tri-O-acetyl-2,6-dideoxy-L-arabino- and -L-lyxo-hexopyranose

Methyl 2,6-dideoxy-α-L-arabino-hexopyranoside (6) was prepared from L-rhamnose in five steps. Hydrolysis of6 with 50% aqueous acetic acid gave 2,6-dideoxy-L-arabino-hexopyranose. Treatment of 3,4-di-O-acetyl-L-rhamnal with acetic acid in the presence of acetic anhydride and 2% sulfuric acid afforded 1,2,3-tri-O-acetyl-2,6-dideoxy-L-arabino-hexopyranose in 65% yield. Selective benzoylation and subsequent mesylation of 6 afforded methyl 3-O-benzoyl-2,6-dideoxy-4-O-mesyl-α-L-arabino-hexopyranoside, which was treated with sodium benzoate and sodium azide in hexamethylphosphoric triamide to give the corresponding 3,4-dibenzoyl 9 and 4-azido 11 analogs. Hydrogenation and N-acetylation of 11 afforded the 4-acetamido derivative 12. Deprotection of 9 and 12 gave 2,6-dideoxy-L-lyxo-hexopyranose and 4-acetamido-2,4,6-trideoxy-L-lyxo-hexopyranose, which were characterized as their peracetates. The free and corresponding peracetylated derivatives were assayed for their ability to inhibit the growth of P388 leukemia cells in culture. Although the free sugars did not inhibit the replication of these tumor cells under the conditions employed, their peracetylated derivatives demonstrated significant activity.     

Synthesis of 2,4-diacetamido-2,4,6-trideoxy-D-Galactose

Treatment of benzyl 2-acetamido-3-O-benzyl-2,6-dideoxy-4-O-(methylsulfonyl)-α-D-glucopyranoside (1) with sodium azide in hexamethylphosphoric triamide gave the 4-azido-α-D-galacto derivative (2), which was converted into benzyl 2,4-di-acetamido-3-O-benzyl-2,3,6-trideoxy-α-D-galactopyranoside (3) by hydrogenation and subsequent acetylation. Hydrogenolysis of 3 at atmospheric pressure afforded benzyl 2,4-diacetamido-2,4,6-tridcoxy-α-D-galactopyranoside (4), which was acetylated to give the 3-O-acetyl derivative (5). The n.m.r. spectrum of 5 was in agreement with the assigned structure and different from that of benzyl 2,4-di-acetamido-3-O-acetyl-α-D-glucopyranoside (9), which was prepared from the known benzyl 2,4-diacetamido-3-O-benzyl-2,4,6-trideoxy-α-D-glucopyranoside. Catalytic hydrogenolysis of 4 gave 2,4-diacetamido-2,4,6-trideoxy-D-galactose (6).     

A synthesis of l-ristosamine and a derivative of its C-4 epimer

A synthesis of l-ristosamine from l-rhamnal is described, involving the sequence of reactions: methoxymercuration, tosylation, azide displacement, and reduction, which gave methyl α-l-ristosaminide (10). Acid hydrolysis then afforded l-ristosamine hydrochloride. Trifluoroacetylation of the hydrochloride of 10 followed by saponification and oxidation with ruthenium tetraoxide gave methyl 2,3,6-tri-deoxy-3-trifluoroacetamido-α-l-erythro-hexopyranosid-4-ulose (17). Borohydride reduction of 17 gave a separable, 1:1 mixture of methyl 2,3,6-trideoxy-3-trifluoroacetamido-α-l-ribo- and α-l-xylo-hexopyranoside.     

Synthesis of new branched-chain aminodeoxyhexoses related to daunosamine (3-amino-2,3,6-trideoxy-l-lyxo-hexose)

Addition of methylmagnesium iodide to methyl 2,3,6-trideoxy-3-trifluoro-acetamido-α-l-threo-hexopyranosid-4-ulose (3) gave methyl 2,3,6-trideoxy-4-C-methyl-3-trifluoroacetamido-α-l-lyxo-hexopyranoside (4) and its l-arabino analogue, depending upon the reaction temperature and the solvent. The corresponding 4-O-methyl derivatives were obtained by treatment of 4 and 5 with diazomethane in the presence of boron trifluoride etherate. Treatment of 4 with thionyl chloride, followed by an alkaline work-up, gave methyl, 2,3,4,6-tetradeoxy-4-C-methylene-3-trifluoro-acetamido-α-l-threo-hexopyranoside (8), which was stereoselectively reduced to methyl 2,3,4,6-tetradeoxy-4-C-methyl-3-trifluoroacetamido-α-l-arabino-hexopyranoside. Epoxidation of 8 with 3-chloroperoxybenzoic acid gave the corresponding 4,4₁-anhydro-4-C-hydroxymethyl-l-lyxo derivative (10), which was also prepared by treatment of 3 with diazomethane. Azidolysis of 10, followed by catalytic hydrogenation and N-trifluoroacetylation, gave methyl 2,3,6-trideoxy-3-trifuloroacetamido-4-C-trifluoroacetamidomethyl-α-l-lyxo-hexopyranoside.     

Synthesis of derivatives of 3-amino-2,3-dideoxy-l-hexoses related to daunosamine (3-amino-2,3,6-trideoxy-l-lyxo-hexose)

The synthesis is described of 3-amino-2,3-dideoxy-l-arabino-hexose (10), methyl 2,3-dideoxy-3-trifluoroacetamido-α-l-lyxo-hexopyranoside (17), methyl 3-amino-2,3-dideoxy-α-l-ribo-hexopyranoside (21), methyl 2,3-dideoxy-3-trifluoroacetamido-α-l-xylo-hexopyranoside (26), and certain derivatives from methyl 4,6-O-benzylidene-2-deoxy-α-l-arabino-hexopyranoside (3). Conversion of 2-deoxy-l-arabino-hexose into 3 by modified, standard procedures, and on a large scale, gave a 75% yield.     

Studies related to the synthesis of derivatives of 2,6-diamino-2,3,4,6-tetradeoxy-D-erythro-hexose (purpurosamine C), a component of gentamicin C12

Reduction of 1,6-anhydro-3,4-dideoxy-β-D-glycero-hex-3-enopyranos-2-ulose (levoglucosenone) with lithium aluminium hydride afforded principally 1,6-anhydro-3,4-dideoxy-β-D-threo-hex-3-enopyranose (3), which was converted into 3,4-dihydro-2(S)-hydroxymethyl-2H-pyran (8) following acid-catalysed methanolysis and reductive rearrangement of the resulting α-glycoside 4 with lithium aluminium hydride. 1,6-Anhydro-3,4-dideoxy-2-O-toluene-p-sulphonyl-β-D-threo-hexopyranose, prepared from 3, reacted slowly with sodium azide in hot dimethyl sulphoxide to give 1,6-anhydro-2-azido-2,3,4-trideoxy-β-D-erythro-hexopyranose, which was transformed into a mixture of methyl 2-acetamido-6-O-acetyl-2,3,4-trideoxy-α-D-erythro-hexopyranoside (10) and the corresponding β anomer following acid-catalysed methanolysis, catalytic reduction, and acetylation. Acid treatment of methyl 4,6-O-benzylidene-3-deoxy-α-D-erythro-hexopyranosid-2-ulose yielded the enone 15, which was readily transformed into methyl 6-O-acetyl-3,4-dideoxy-α-D-glycero-hexopyranosid-2-ulose (19). Procedures for the conversions of DL-8, 10, and 19 into methyl 2,6-diacetamido-2,3,4,6-tetradeoxy-α-D-erythro-hexopyranoside (methyl N,N′-di-acetyl-α-purpurosaminide C) have already been described.     

Synthesis of acetylenic sugars and uronic acids via two-carbon chain extension of d-ribose

Treatment of methyl β-d-ribofuranoside with acetone gave methyl 2,3-O-isopropylidene-β-d-ribofuranoside (1, 90%), whereas methyl α-d-ribofuranoside gave a mixture (30%) of 1 and methyl 2,3-O-isopropylidene-α-d-ribofuranoside (1a). On oxidation, 1 gave methyl 2,3-O-isopropylidene-β-d-ribo-pentodialdo-1,4-furanoside (2), whereas no similar product was obtained on oxidation of 1a. Ethynylmagnesium bromide reacted with 2 in dry tetrahydrofuran to give a 1:1 mixture (95%) of methyl 6,7-dideoxy-2,3-O-isopropylidene-β-d-allo- (3) and -α-l-talo-hept-6-ynofuranoside (4). Ozonolysis of 3 and 4 in dichloromethane gave the corresponding d-allo- and l-talo-uronic acids, characterized as their methyl esters (5 and 6) and 5-O-formyl methyl esters (5a and 6a). Ozonolysis in methanol gave a mixture of the free uronic acid and the methyl ester, and only a small proportion of the 5-O-formyl methyl ester. Malonic acid reacted with 2 to give methyl 5,6-dideoxy-2,3-O-isopropylidene-β-d-ribo-trans-hept-5-enofuranosiduronic acid (7).     

Synthesis of phenyl 2-acetamido-2-deoxy-3-O-α-l-fucopyranosyl-β-d-glucopyranoside and related compounds

The reaction of phenyl 2-acetamido-2-deoxy-4,6- O-(p-methoxybenzylidene)-β-d-glucopyranoside with 2,3,4-tri-O-benzyl-α-l-fucopyranosyl bromide under halide ion-catalyzed conditions proceeded readily, to give phenyl 2-acetamido-2-deoxy-4,6-O-(p-methoxybenzylidene)-3-O-(2,3,4-tri-O-benzyl-α-l-fucopyranosyl)-β-d-glucopyranoside (8). Mild treatment of 8 with acid, followed by hydrogenolysis, provided the disaccharide phenyl 2-acetamido-2-deoxy-3-O-α-l-fucopyranosyl-β-d-glucopyranoside. Starting from 6-(trifluoroacetamido)hexyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-d-glucopyranoside, the synthesis of 6-(trifluoroacetamido)hexyl 2-acetamido-2-deoxy-3-O-β-l-fucopyranosyl-β-d-glucopyranoside has been accomplished by a similar reaction-sequence. On acetolysis, methyl 2-acetamido-2-deoxy-3-O-α-l-fucopyranosyl-α-d-glucopyranoside gave 2-methyl-[4,6-di-O-acetyl-1,2-dideoxy-3-O-(2,3,4-tri-O-acetyl-α-l-fucopyranosyl)-α-d-glucopyrano]-[2, 1-d]-2-oxazoline as the major product.     

An application of the palladium-catalyzed,allylic amination of unsaturated sugars: a new synthesis of d-forosamine

Methyl 4-O-benzoyl-6-bromo-6-deoxy-α-d-glucopyranoside, obtainable from methyl 4,6-O-benzylidene-α-d-glucopyranoside (1), was converted into the 2,3-unsaturated 4-benzoate (3) by application of the triiodoimidazole method. Debenzoylation of 3, followed by acetylation, afforded crystalline methyl 4-O-acetyl-6-bromo-2,3,6-trideoxy-α-d-erythro-hex-2-enopyranoside (5). Treatment of 5 with benzylmethylamine under conditions of palladium-catalyzed, allylic substitution gave a separable mixture of the corresponding 4-(N-benzyl)methylamino-6-bromo-2-enoside (37%) and the 4,6-di-[(N-benzyl)methylamino]-2-enoside (55%). Debromination of 5 with lithium triethylborohydride, proceeding with simultaneous deacetylation, readily yielded methyl 2,3,6-trideoxy-α-d-erythro-hex-2-enopyranoside (8). The 4-acetate of 8 (obtained by reacetylation), and also its 4-benzoate (prepared by a different synthetic route), furnished high yields (～80%) of methyl 4-[(N-benzyl)-methylamino]-2,3,4,6-tetradeoxy-α-d-erythro-hex-2-enopyranoside (13) upon palladium-catalyzed animation with benzylmethylamine. Catalytic hydrogenation of 13 effected saturation of the alkenic double bond and removal of the N-benzyl group, to afford methyl 2,3,4,6-tetradeoxy-4-methylamino-α-d-erythro-hexopyranoside, which was subsequently N-methylated with formaldehyde and sodium borohydride, to give its N,N-dimethyl analog, methyl α-d-forosaminide (15). The overall yield of 15 from 1 was 24%. Hydrolysis of 15 to the free sugar has been described previously.     

Synthesis of 3-O Substituted D-Mannoses

1,2,4,6-Tetra-O-acetyl-3-O-benzyl-α-D-mannopyranose (7) was obtained in good yield from 3,4,6-tri-O-benzyl-1,2-O-(1-methoxyethylidene)-β-D-mannopyranose (1) by acetolysis. Hydrogenolysis of 7 afforded 1,2,4,6-tetra-O-acetyl-α-D-mannopyranose which is a versatile intermediate for the preparation of other 3-O-substituted D-mannoses, such as 3-O-methyl-D-mannose and 3-O-α-D-mannopyranosyl-D-mannose. 3,4-Di-O-methyl-D-mannose was readily prepared from 1,2,6-tri-O-acetyl-3,4-di-O-benzyl-α-D-mannopyranose, which was also obtained from 1 by controlled acetolysis.     

Ring-opening reactions of sucrose epoxides: Synthesis of 4′-derivatives of sucrose

The 2,1′-O-isopropylidene derivative (1) of 3-O-acetyl-4,6-O-isopropylidene-α-d-glucopyranosyl 6-O-acetyl-3,4-anhydro-β-d-lyxo-hexulofuranoside and 2,3,4-tri-O-acetyl-6-O-trityl-α-d-glucopyranosyl 3,4-anhydro-1,6-di-O-trityl-β-d-lyxo-hexulofuranoside have been synthesised and 1 has been converted into 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 1,6-di-O-acetyl-3,4-anhydro-β-d-lyxo-hexulofuranoside (2). The S_N2 reactions of 2 with azide and chloride nucleophiles gave the corresponding 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 1,3,6-tri-O-acetyl-4-azido-4-deoxy-β-d-fructofuranoside (6) and 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 1,3,6-tri-O-acetyl-4-chloro-4-deoxy-β-d-fructofuranoside (8), respectively. The azide 6 was catalytically hydrogenated and the resulting amine was isolated as 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 4-acetamido-1,3,6-tri-O-acetyl-4-deoxy-β-d-fructofuranoside. Treatment of 5 with hydrogen bromide in glacial acetic acid followed by conventional acetylation gave 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 1,3,6-tri-O-acetyl-4-bromo-4-deoxy-β-d-fructofuranoside. Similar S_N2 reactions with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 1,6-di-O-acetyl-3,4-anhydro-β-d-ribo-hexulofuranoside (12) resulted in a number of 4′-derivatives of α-d-glucopyranosyl β-d-sorbofuranoside. The regiospecific nucleophilic substitution at position 4′ in 2 and 12 has been explained on the basis of steric and polar factors.     

Chain elongation by a seemingly stereospecific cyanohydrin synthesis: the preparation and configurational assignment of 3,7-anhydro-d-threo-l-talo- and -l-galacto-octose

2,6-Anhydro-d-glycero-l-manno-heptose (1) is converted by the cyanohydrin reaction into crystalline d-threo-l-talo-octononitrile (3), which shows mutarotation in water. The equilibrium mixture, as measured by ¹³C-n.m.r. spectroscopy, contains about equal amounts of 3 and its epimer, d-threo-l-galacto-octononitrile. On evaporation of the aqueous mixture, pure, crystalline 3 is again obtained. Labelling experiments in ³H₂O proved that epimerization proceeds through reversible deprotonation. Stabilization of 3 in the solid state is explained by intramolecular hydrogen-bonding. In pyridine, rapid isomerization of 3 occurs. When acetylation of 3 is conducted in this solvent, the yield of 2,4,5,6,8-penta-O-acetyl-3,7-anhydro-d-threo-l-talo-octono-nitrile (4) depends strongly on the conditions of acetylation. Acetylation after equilibration produces an equimolar mixture of 4 and its isomer 2,4,5,6,8-penta-O-acetyl-3,7-anhydro-d-threo-l-galacto-octononitrile. Structural assignment for both was achieved by 360-Mhz, ¹H- and ¹³C-n.m.r. spectroscopy. Reduction of 4 in pyridine-acetic acid-water in the presence of N,N-diphenylethylenediamine yields a 1:2.36 mixture of 2,4,5,6,8-penta-O-acetyl-3,7-anhydro-d-threo-l-talo-octose N,N-diphenylimidazolidine (6) and 2,4,5,6,8-penta-O-acetyl-3,7-anhydro-d-threo-l-galacto-octose N,N-diphenylimidazolidine (8). Compounds 6 and 8 could be separated and obtained as crystalline solids, and their structure proved by ¹H- and ¹³C-n.m.r. spectroscopy. Hydrolysis of 6 and 8 gave 2,4,5,6,8-penta-O-acetyl-3,7-anhydro-d-threo-l-galacto-octose and -d-threo-l-talo-octose.