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.     

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.     

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.     

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.     

Methylation of nitro sugars with diazomethane,and preparation of some new amino sugar methyl ethers

Diazomethane reacted with methyl 3,6-dideoxy-3-nitro-α-l-glucopyranoside (1) under catalysis by boron trifluoride to give the 2-O-methyl and the 2,4-di-O-methyl derivative (2 and 3). Similarly, the 4-acetate (4) of 1 afforded the 4-acetate (5) of 2. Boron trifluoride-catalyzed acetylation of 2 at about ?60° gave 5 whereas, at 0°, acetolysis took place producing 1,4-di-O-acetyl-3,6-dideoxy-2-O-methyl-3-nitro-α-l-glucopyranose (6). Diazomethane treatment of methyl 3,4,6-trideoxy-3-nitro-α-l-erythro- and -α-l-threo-hex-3-enopyranosides 7 and 8 furnished the corresponding 2-O-methyl derivatives 9 and 10. With triphenylphosphine and carbon tetrachloride, 2 yielded methyl 4-chloro-3,4,6-trideoxy-2-O-methyl-3-nitro-α-l-galactopyranoside (11) which was dehydrochlorinated to 9. Borohydride reduction of 9 gave methyl 3,4,6-trideoxy-2-O-methyl-3-nitro-α-l-xylo-hexopyranoside (12). Catalytic hydrogenation of 3 and 12 afforded the corresponding amino sugar hydrochlorides 13 and 15. Treatment of 5 with ammonia gave a 4-amino-3-nitro glycoside (isolated as the hydrochloride 17) hydrogenation of which led to methyl 3,4-diamino-3,4,6-trideoxy-2-O-methyl-α-l-glucopyranoside dihydrochloride (19). The N-acetyl derivatives (14, 16, 18, and 20) of the four new amino sugars were prepared.     

Synthesis of 3-amino-2,3,6-trideoxy-d-ribo- and -l-lyxo-hexofuranoses suitable for nucleoside synthesis

N-Acetylepidaunosamine (3-acetamido-2,3,6-trideoxy-d-ribo-hexopyranose) was converted into the diethyl dithioacetal and this was cyclized with HgCi₂, HgO, and MeOH, to give methyl 3-acetamido-2,3,6-trideoxy-α- and -β-d-ribo-hexofuranoside (4 and 5). These anomers were acetylated or (p-nitrobenzoyl)ated, and the esters were subjected to acetolysis, to afford 3-acetamido-1,5-di-O-acetyl-2,3,6-trideoxy-d-ribo-hexofuranose and 3-acetamido-1-O-acetyl-2,3,6-trideoxy-5-O-(p-nitrobenzoyl)-d-ribo-hexofuranose, respectively. Alternatively, compounds 4 and 5 were hydrolyzed to the free bases with barium hydroxide, and these were converted into the trifluoroacetamido derivatives which, on (p-nitrobenzoyl)ation and acetolysis, afforded 1-O-acetyl-2,3,6-trideoxy-5-O-(p-nitrobenzoyl)-3-(trifluoroacetamido)-d-ribo-hexofuranose. To prepare the corresponding daunosamine derivative, 2,3,6-trideoxy-3-(trifluoroacetamido)-l-lyxo-hexopyranose was converted into the diethyl dithioacetal, and this was cyclized in the same way, to afford methyl 2,3,6-trideoxy-3-(trifluoroacetamido)-α- and -β-l-lyxo-hexofuranoside. On (p-nitrobenzoyl)ation and acetolysis, both afforded 1-O-acetyl-2,3,6-trideoxy-5-O-(p-nitrobenzoyl)-3-(trifluoroacetamido)-l-lyxo-hexofuranose.     

A new synthesis of 4-O-α-d-galactopyranosyl-d-galactopyranose

The bromide-catalyzed condensation of 2,3,4,6-tetra-O-benzyl-d-galactopyranosyl bromide (11) with methyl 2,3,6-tri-O-benzoyl-α-d-galactopyranoside (3) gave methyl 2,3,6-tri-O-benzoyl-4-O-(2,3,4,6-tetra-O-benzyl-α-d-galactopyranosyl)-α-d-galactopyranoside (12) in 83% yield. The yield of this glycosidation reaction was high, despite the axial orientation of the 4-hydroxyl group of 3. Stepwise deprotection of 12 afforded methyl 4-O-α-d-galactopyranosyl-α-d-galactopyranoside (15). Acetylation of 15, followed by acetolysis, gave the known α-octaacetate 17. This scheme constituted a total synthesis of 4-O-α-d-galactopyranosyl-d-galactopyranose (2) in 25% yield from 3. The disaccharide 2 is the terminal disaccharide of the ceramide trisaccharide related to Fabry's disease.     

Preferential sulfonylation of methyl 2,6-di-O-mesyl-α-D-glucopyranoside

When equimolar ratios of mesyl chloride and methyl 2,6-di-O-mesyl-α-D-glucopyranoside were allowed to react in pyridine and the product resolved by preparative t.l.c., the 2,6-di-, 2,3,6-tri-, 2,4,6-tri-, and 2,3,4,6-tetra-mesyl esters were obtained in (0.5–0.6):1:(4–5):(1-2-1.4) molar ratio. Benzoylation of either the isolated 2,4,6-tri-O-mesyl ester or, more conveniently, the mixture from monomesylation gave the crystalline methyl 3-O-benzoyl-2,4,6-triO-mesyl-α-D-glucopyranoside (8). As both of these trimesyl esters (7 and 8) are unreported, isolation of the benzoate established the 2,4,6-ester arrangement, and the 2,3,6-triester was prepared by standard methods. Treating methyl α-D-glucopyranoside with 3 molar equivalents of mesyl chloride and, subsequently, with 1 molar equivalent of benzoyl chloride, proved a convenient method for preparing the 3-O-benzoyl derivative in moderate yield. Monotosylation of methyl 2,6-di-O mesyl-α-D-glucopyranoside was not so definitive as mesylation, but a molar ratio of 1:2.8 for the 3-O-tosyl:4-O-tosyl product was derived from n.m.r. data. This work, when combined with literature reports, establishes that, in methyl α-D-glucopyranoside, the reactivity toward sulfonylation is 6-OH>2-OH>4-OH>3-OH.     

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).     

Synthèse et réactivite du méthyl-2-O-benzoyl-3-bromo-3,6-didésoxy-α-l-altropyranoside et du méthyl-2-O-benzoyl-3-bromo-3,6-didésoxy-4-O-méthyl-α-l-altropyranoside

Methyl 2-O-benzoyl-3-bromo-3,6-dideoxy-α-l-altropyranoside (4) and methyl 2-O-benzoy]-3-bromo-3,6-dideoxy-4-O-methyl-α-l-altropyranoside (5) have been prepared from methyl-α-l-rhamnopyranoside, respectively, in 2 and 3 steps. Reduction of 4 with lithium aluminium hydride followed by acid hydrolysis afforded the 3,6-dideoxy-l-arabino-bexose (l-ascarylose). The anhydro sugars 8 and 9 have been used as intermediates in the stereoselective synthesis of 6-deoxy-3-O-methyl-l-altropyranose (l-vallarose) and of 3-amino-3-degxy-l-altro sugars. Under azidolysis conditions, and according to the temperature, 5 gave unsaturated sugars such as 20 and the derived 26, or azido compounds such as 21 and 24, and the derived sugar methyl 2-amino-2,3,6-trideoxy-α-l-threo-hexopyranosid-4-ulose (25).     

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).     

Aminoglycosides of D-pinitol. The 3-amino-3-deoxy-α-D-glucopyranoside,THE 3-acetamidino analog,and the 3,6-dideoxy-3,6-epimino-α-D-glucopyranoside

3-Azido-2,4,6-tri-O-benzyl-3-deoxy-α-D-glucopyranosyl chloride (7), prepared conventionally from the azido precursor 2, was coupled with “diisopropylidene-D-pinitol” (8) to give the α-D-glucoside 9 in good yield, together with some β anomer. Removal of the O-benzyl groups from 9 and reduction of the azido group to ?NH₂ were accomplished simultaneously. Further deprotection yielded 11, a 3-amino-3-deoxy-α-D-glucoside of D-pinitol (1a). Compound 11 was converted into the (impure) 3-acetamidino hydrochloride 12. The synthesis of 3,6-epimino-D-glucosides was accomplished by ring closure of the 3-N-tosyl-6-O-tosyl intermediates 17 and 13. The products, after deprotection, were methyl 3,6-dideoxy-3,6-epimino-β-D-glucopyranaside (20) and the novel 3,6-epimino analog 15 of the pinitol D-glucoside 11.     

Formation of 3-octuloses by a self-aldol reaction of d-erythrose

When kept at 105° for 2.5 h, weakly alkaline, syrupy d-erythrose was readily converted into a mixture containing mainly d-glycero-tetrulose, the previously unknown β-d-altro-l-glycero-3-octulofuranose (2), and α-d-gluco-l-glycero-3-octulopyranose, which were isolated as the corresponding acetates. Treatment of 2 with Dowex 50 (H⁺) resin yielded 3,8-anhydro-β-d-altro-l-glycero-octulopyranose, identified as its acetate. Previous discrepancies in the [α]_d values for d-erythrose appear partly to originate in the self-aldol reaction. The dimerisation of d-erythrose 4-phosphate is also described.     

The synthesis of 3-amino-2,3,6-trideoxy-l-xylo-hexopyranose derivatives

Derivatives (the 3-acetamido-4-benzoate 12, the 3-acetamido-4-acetate 13, and the N-acetyl derivative 14) of the methyl glycoside of the title sugar were prepared in a sequence of high-yielding steps from methyl 3-azido-4,6-O-benzylidene-2,3-di-deoxy-α-d-arabino-hexopyranoside (4). N-Bromosuccinimide converted 4 into the crystalline 4-O-benzoyl-6-bromide 5, which was treated with silver fluoride to afford the 5,6-unsaturated glycoside 6. Catalytic hydrogenation of 6 led, essentially, to a 7:1 mixture of 12 and its 5-epimeric d-arabino isomer 7. Alternatively, 6 was debenzoylated to 10, and the latter treated with lithium aluminum hydride to give crystalline methyl 3-amino-2,3,6-trideoxy-α-d-threo-hex-5-enopyranoside (11). Reduction of 11 (as its salt) by hydrogen, with subsequent N-acetylation, furnished the methyl β-l-xylo-glycoside 13 almost exclusively, with net inversion at C-5. Compound 13 was readily converted into the crystalline target compound 14. When dehydrobromination by silver fluoride was attempted with the 3-acetamido analog (2) of 5, a 3,6-anhydro product (1) was obtained, instead of the expected 5,6-alkene 3.     

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 5-deoxy-β-d-galactofuranosides as tools for the characterization of β-d-galactofuranosidases

Derivatives of 5-deoxy-β-d-galactofuranose (5-deoxy-α-l-arabino-hexofuranose) have been synthesized starting from d-galacturonic acid. The synthesis of methyl 5-deoxy-α-l-arabino-hexofuranoside (14α) was achieved by an efficient strategy previously optimized, involving a photoinduced electron transfer (PET) deoxygenation. Compound 14α was converted into per-O-acetyl-5-deoxy-α,β-l-arabino-hexofuranoside (16), an activated precursor for glycosylation reactions. The SnCl₄-promoted glycosylation of 16 led to 4-nitrophenyl (19α), and 4-methylthiophenyl 5-deoxy-α-l-arabino-hexofuranosides (20α). The oxygenated analog 4-methylphenyl 1-thio-β-d-galactofuranoside (23β) was also prepared. The 5-deoxy galactofuranosides were evaluated as inhibitors or substrates of the exo-β-d-galactofuranosidase from Penicillium fellutanum, showing that the absence of HO-5 drastically diminishes the affinity for the protein.     

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.     

The stereochemistry of palladium- and platinum-catalyzed hydrogenations of nitro sugar epoxides

The catalytic hydrogenation of carbohydrate α-nitroepoxides with palladium and platinum was investigated with regard to regiospecificity and stereochemistry of ring opening, and the fate of the nitro group. 5,6-Anhydro-1,2-O-isopropylidene- 6-C-nitro-α-D-glucofuranose gave 6-amino-6-deoxy-1,2-O-isopropylidene-α-D-gluco-furanose under platinum catalysis. The methyl 2,3-anhydro-4,6-O-benzylidene-3-C- nitrohexopyranosides having the β-D-gulo (4), ?-D-allo (9), α-D-manno (13), and β-D-manno (18) configurations underwent facile, hydrogenolytic ring-opening in the presence of palladium, to give, regardless of the orientation of the oxirane ring, methyl 4,6-O-benzylidene-3-deoxy-3-C-nitro-D-hexopyranosides having an equatorial nitro group (5, 10, 14, and 19, respectively). In addition, 3-deoxy-3-oximino derivatives arose in various proportions, and two of these (from 9, and from 18) were isolated crystalline. It was shown that the oximes did not result from over-hydrogenation of the 3-deoxy-3-C-nitro glycosides produced, and it is suggested that they originated from intermediary nitronic acids. By catalysis with platinum, the oxirane rings in 4, 9, 13, and 18 were opened in the same regiospecific sense as with palladium, but notable differences were observed otherwise. Compound 4 gave the amino analog of 5, whereas 9 retained the nitro group and gave the 4,6-O-(cyclohexylmethylene) analog of 10. The α-D-manno epoxide 13 reacted with concomitant debenzylidenation, to yield methyl 3-amino-3-deoxy-α-D-altropyranoside hydrochloride, whereas the β-D-manno epoxide 18 gave the corresponding, debenzylidenated amino β-D-altroside together with the 4,6-O-(cyclohexylmethylene)-3-nitro- and -3-amino-β-D-mannosides. The results are compared with literature reports on the stereochemistry of hydrogenolysis of oxiranes, and mechanisms that may operate for the nitro derivatives are discussed.