Synthesis of D-Idurone

Abstract

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.

Epimerization of Monosaccharides in Acetic Acid and Acetic Anhydride. Synthesis of D-Altrose

“…With a longer reaction time of 89 h, the results were virtually unchanged; the yield of D-altrose was 41% and the D-altrose to D-allose ratio was 1.3 to 1. The high conversion of 1,2;5,6-di-0-isopropylidene-a-D-allofuranose to D-altrose supports the suggestion that the acetolysisinversion reaction occurs via the furanose form of a monosaccharide in which a cisorientation of groups is capable of assuming a trans-orientation through acetoxonium ion intermediates (3,4).…”

“…the observation that monosaccharides with a cis-configuration at C-2 and -3 generally form a mixture of C-2 epimers in an acetolysis medium containing a high concentration of acetic acid (ca. 90%) (3). This cis to trans conversion was first noted by Jerkeman with D-mannofuranose derivatives (4).…”

Epimerization of Monosaccharides Under Acetolysis Conditions

“…were p-anisidine hydrochloride (25) and silver nitrate -sodium hydroxide (26). Dibenzyl dithioacetals were prepared by treatment of the sugar with toluenethiol in the presence of trifluoroacet~c acid (27) for 2 h at room temperature, followed by evaporation of the mixture to dryness. Acefolysis of2,3;5,6-Di-0-isopropylidene-D-gulofuranose 2,3;5,6-Di-0-isopropylidene-D-gulofuranose was prepared by sodium borohydride reduction of 2,3;5,6-di-0-isopropylidene-D-gulonolactone in ether containing acetic acid (10).…”

Carbene radical anions. New species of reactive intermediate

“…Caled for [Ir(NH3)5NH2Cl](C104)3: N, 13.40; H, 2.73; NH2C1, 8.21; CIOr, 47.57. Found: N, 12.93; H, 2.56; NHiCl, 7.75; ClOr, 47.48.…”