Polysaccharide sulfates. II. Sulfuric acid esters of glycuronans having various degrees of substitution

Abstract

By use of an N,N-dimethylformamide-sulfur trioxide complex in N,N-dimethylformamide as a solvent, and after proper activation, alginic and pectic acids are sulfated without difficulty up to a degree of substitution (d.s.) of about 1.8. Lower d.s. levels are obtained by decreasing the proportion of complex. Degradation, as indicated by viscosity measurements, is minor. All sulfated glycuronans exhibit reactivity with proteins that becomes more pronounced as the d.s. increases. Solutions of algin sulfates having d.s. >1.0 gelatinize in the presence of the heavier alkali-metal ions. Only two other polysaccharide sulfates, K -carrageenan and cellulose sulfate, prepared recently, exhibit such properties. Among the polysaccharides, glycuronans present the most difficulties for the substitution of their hydroxyl groups. For example, conventional methods of acetylating alginic acid [composed of β- D-(1→4)-linked D-mannuronic 1.2 and L-guluronic 3 acid residues], and pectic acid (a D-galacturonan 4) were unsuccessful 5. Under more rigorous conditions, highly degraded products usually result. Although the close proximity of the electronegative carboxyl group may be responsible to some extent for this lack of reactivity, it has been proposed recently that the principal reason is the extensive formation of hydrogen bonds between hydroxyl groups. It was shown that alginic acid 6 and pectic acid 7 could be acetylated without difficulty after the extent of hydrogen bonding had been decreased; that is, the acids had been properly “activated”. In sulfation of a glycuronan, not only is the lack of reactivity of the polymer a handicap but, additionally, the usual conditions for sulfation are vigorous and apt to degrade polysaccharides. Thus, Whistler and Spencer 8 could not esterify alginic acid by use of a triethylamine-sulfur trioxide complex. Apart from a few patents describing the preparation of highly degraded algin sulfates 9 and pectin sulfates 10 to be used as blood anticoagulants, no other reports of a successful method for sulfating glycuronans has appeared in the literature so far. In the preceding article of this series 11, a new method of sulfating cellulose was reported. A complex of acid sulfates and that of alginic acid sulfate having a d.s. of 1 did not gelatinize at any temperature. The results from the algin sulfate having a d.s. of 1.5 are given in Table III.