A mild method for the hydrolysis of acetal groups attached to sugars and nucleosides

L-Iduronic acid is a major constituent of the anticoagulant heparin according to recent evidence obtained from chemical degradation studies (1) and by 220 MHz p.m.r. spectroscopy (2). Contrary to earlier work (3-6), D-glucuronic acid appears to be a minor rather than a major component of the mucopolysaccharide. The p.m.r. data at 220 MHz confirm that L-idosyluronic acid residues occur also in dermatan (chondroitin sulfate B) and possibly heparitin (2).Synthetic L-iduronic acid is not readily available. It has been prepared by application of the cyanohydrin synthesis to 1,2-0-isopropylidenea-D-xylo-pentodialdo-1 ,Cfuranose, the product of periodate oxidation of 1,2-0-isopropylidenea-D-glucofuranose (7). In this procedure 1,2-0-isopropylidene-P-L-idofuranurono-6,3-lac is separated from the co-product, 1,2-0-isopropylidene-a-D-glucofuranurono-6,3-lactone, by columnchromatography onclay. Reported recently is an alternative synthesis also based on chain extension of 1 ,2-0-isopropylidene-a-D-xylo-pentodialdo-1,Cfuranose (8). The xylo derivative, or its 3-benzyl ether, is ethynylated to yield a mixture of 5-epimeric, 7-carbon acetylenic sugars. The epimeric heptynes are separated by fractional distillation or by silica gel chromatography and converted by ozonolysis into derivatives of D-glucuronic and L-iduronic acids.For many purposes in investigations of natural polymers containing L-iduronic acid, the enantiomer would serve as a reference compound. as in the preparation of L-glucurone (9). D-Idurone was isolated by preparative paper chromatography. On a millimolar scale, the yield was around 50%. A useful crystalline derivative is the dibenzyl dithioacetal. To minimize degradation of the uronic acid, it was advantageous to use trifluoroacetic acid instead of hydrochloric acid as a catalyst for thioacetalation.The preparation of D-idurone was further simplified by oxidizing a mixture of D -~~Y c~~o ido-heptonolactone and D-glycero-D-gulo-heptonolactone, thus avoiding isolation of pure ido starting material. The mixture of heptonolactones was easily obtainable either from D-glucose by the cyanohydrin synthesis (10) or by epimerization of commercially-available D-glycero-D-guloheptonolactone with pyridine. After periodate oxidation of the mixed lactones, both D-idurone and L-glucurone were isolated by paper chromatography in butanol-ethanol-water (5 :2: 1 v/v), a solvent system in which they are widelyseparated.The straightforward resolution of D-idurone Can. J. Chem. Downloaded from www.nrcresearchpress.com by 54.245.55.244 on 05/11/18For personal use only.

Section: D-idurolze From D-glycero-d-ido-heptonolactolrementioning

confidence: 99%

Synthesis of D-Idurone

Sowa¹

1971

“…Both compou~lds were obtained crystalline. The disaccharides (I to 6) were prepared from the di-0-isopropylider?e derivatives by hydrolysis of the isopropylidene groups using aqueous triAuoroacetic acid (6) followed by chromatographic purification using an ion-exchange resin in the potassium salt from 47). Although none of the disaccharides was obtained crystalline, all provided the expected hexoses (or hexose) on acid Can.…”

mentioning

confidence: 99%

Chemical Syntheses of α-Linked Disaccharides

Lemieux¹,

James²,

Nagabhushan³

1973

Chemical syntheses of six a-linked disaccharides are described, namely, 6-0-(a- [Traduit par le journal]DCan J Cheili 51 J? (1973) This paper presents syntheses of the six a-linked disaccharides (I to 6) from previously reported (1) oximino-disaccharide structures; namely, the tri-0-acetyl-2-oxin7ino-a-D-arabiko-hexopyranosyl and tri-0-acetyl-2-oxirnino-a-D-/jlxo-hexopyranosyl derivatives of 1,2;5,6-di-0-isopropyiidene-a-D-glucofuranose and of 1,2;3,4-di-0-isopropylidene-a-D-galaclopyranose. The latter compounds were deoximated (2) and the resulting ketonic substances were reduced with sodium borohydride (3) without prior purification. In the preparation of compounds 4, 5, and 6, the use of acetaldehyde in acetonitrilehydrochloric acid reagent (2) for deoximation caused substantial loss of the acid labile 5,6-0-isopropylidene protecting group. However, in the preparation of compounds 1, 2, and 3, deoxirnation under similar conditions caused only small losses of the 0-In view of the high degree of stereoselectivity observed in the reductions to a-D-glucopyranosides (3), the preparations of compounds B and 4 proceeded with little difficulty in 54 and 67% yields, respectively. Although both the interme-propylidene-a-u-galactopyranose and its tetraacetate failed to crystallize, both 3-0-(a-D-glucopyranosyl) -1,2 i5.6-di-0-isopropylidene-a-D-glucofuranose and its tetraacetate were obtained in crystalline condition.As previously reported (3), the reduction of a tri-0-acetyl-a-D-lyxo-hexosuloside with sodium borohydride leads to a mixture of galactosides and talosides. 6-0-(Tetra-0-acetyl-x-D-galactopyranosyl) -1,2:3,4-di-0-isopropylidene-a -D-galactopyranose was obtained crystalline in 51%yield and was readily separated from 6-0-(tetraisopropylidene groups. Treatment of the crude 0-acetyl-a-D-talopyranosy1)-1 ,2:3,4-di-0-isoproketones in these cases with 2,2-dirnethoxypropane pylidene-a-D-galactopyranose (30$/: yield as a andp-to!uenesulfonic acid monohydrate re-intro-syrup) by column chromatography on silicic acid. duced these groups in near quantitative yields. This was not the case in the preparation of compounds 4, 5, and 6. Therefore, lor the syl~tllesis of these compounds deoximation under neutral conditions with titanium trichloride (3, 4) was used. Reduction followed by 0-acetylation enabled compounds 1 to 4 to be isolated as the O-(tetra-8-acetyl-31-~-P1exopyranosy~)-di-0-isopropylidene-D-hexoses. 'Presented at the ihlst National American Chemical Society Meeting, Eos Angeles, California, March 28,1971. 'University of Alberta Postdoctoral Fellow, 1970. 3Professional Research Associate, 1970 Column chromatography on a resin in the hydroxide fornu (5) was used to separate 3-0-(a-Dgalactopyranosyl) -1,2:5,6-di -0 -isopropylidener-D-glucofuranose from the talo-isomer. Both compou~lds were obtained crystalline. The disaccharides (I to 6) were prepared from the di-0-isopropylider?e derivatives by hydrolysis of the isopropylidene groups using aqueous triAuoroacetic acid (6) followed by chromatographic purificat...

“…The starting compounds 1 (6), 2 (7), 3 (9), I0 (6), 12 (lo), the L-enantiomer of 12 (ll), and 13 (10) were prepared as previously reported. Melting points were taken in capillaries in an electric aluminium block apparatus.…”

Section: Methodsmentioning

confidence: 99%

“…Another sample of 15 (45 mg) was treated at room temperature with 1 ml of 90% trifluoroacetic acid (12) in which it dissolved within 10min. After 45 min the solution was concentrated in uacuo (bath temperature, 30") to 0.5 ml.…”

Section: Metliyl3-deoxymentioning

confidence: 99%

Reactions of nitro sugars. XII. A novel type of disaccharide synthesis

Baer¹,

Kienzle²

1969

Nitro disaccharide methyl glycosides were obtained by base-catalyzed addition of partially blocked sugar derivatives having one free hydroxyl group, across the ethylenic bond in methyl 4,6-O-benzylidene-2,3-dideoxy-3-nitro-β-D-erythro-hex-2-enopyranoside (1) and its α-anomer (2). Thus, the addition of 2,3,4,6-tetra-O-acetyl-β-D-glucopyranose (3) gave blocked derivatives of sophorose, namely methyl 2-O-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-4,6-O-benzylidene-3-deoxy-3-nitro-β-D-glucopyranoside (4) and -α-D-glucopyranoside (5). Similarly, the use of methyl 4,6-O-benzylidene-3-deoxy-3-nitro-β-D-glucopyranoside (10) and its α-anomer (13) as addends led to 2 → 2 linked bisglycosidyl ethers; these were the methyl 4,6-O-benzylidene-3-deoxy-2-O-(methyl 4,6-O-benzylidene-2,3-dideoxy-3-nitro-D-gluco-pyranosid-2-yl)-3-nitro-D-glucopyranosides with the anomeric configurations β,β, α,α, and α,β (11, 14, and 15, respectively). Methyl 4,6-O-benzylidene-3-deoxy-3-nitro-β-D-mannopyranoside (12) was found to epimerize to 10 under the reaction conditions; therefore, interaction of 12 and 1 also gave the bis-β-D-glucosidyl ether (11). The L-enantiomer of 12 gave with 1 an optically inactive meso compound (16) possessing a β-L- and a β-D-glucosidyl moiety.