Patent GB-796737-A (GB)
Title: A process for the production of glycan poly-(sulphuric acid esters)
IPC: C08B37/00
Filed: 1955-09-09
Abstract: Polysaccharide poly-(sulphuric acid esters), in which any primary amino groups therein are at least partially formylated, are produced by reacting a polysaccharide or a salt thereof with pyridine-(sulphur trioxide), with oleum, or with a mixture of oleum and pyridine, in the presence of formamide as a solvent. Suitable polysaccharides are laevan, partially degraded starch, chondroitin-sulphuric acid, polyuronic acids, e.g. pectic acid and alginic acid, and polyamino sugars, e.g. chitosan. Polysaccharides containing basic or acid groups are preferably used in the form of alkali metal salts, or organic or inorganic acid salts, e.g. formate, acetate or hydrochloride.  The starting material is dissolved in formamide and either treated with oleum at 0 DEG  to 25 DEG  C., preferably 5 DEG to 10 DEG  C., or heated with oleum and pyridine, or treated with pyridine-(sulphur trioxide), preferably at 30 DEG  to 110 DEG  C. Polysaccharides which contain primary amino groups are partially formylated due to the partial decomposition of the formamide into formic acid and ammonia by the sulphating agent.  In order to modify the physical properties of the product, a degradation step, e.g. using hydrogen peroxide, acids or alkali, may be effected before or after the sulphation step.  The degraded material may be fractionated before or after sulphation by fractional precipitation or fractional dissolution. Thus the polysaccharide salt or poly-(sulphuric acid ester), preferably the alkali metal salt of the latter, may be dissolved in water and treated with varying amounts of a water-miscible precipitating agent, e.g. methanol, ethanol, or acetone, to precipitate higher or lower molecular weight fractions as desired.  The poly-(sulphuric acid esters) may be recovered from the sulphation reaction mixture by precipitation with a water-miscible agent such as methanol and taken up in water.  The solution is adjusted to pH 9 with sodium hydroxide forming the sodium salt which may be converted to an alkaloid salt for further purification and then reconverted to the sodium salt.  The products are blood anticoagulating agents having activity related to heparin.  In examples: (1) chitosan formate is degraded by heating with aqueous hydrogen peroxide and then dissolved in formamide and treated with oleum at 5 DEG  to 10 DEG  C., the product being precipitated with methanol, dissolved in water and converted to the sodium salt, purified in the form of the narcotine salt treated with soda solution and then with glacial acetic acid to yield chitosan poly-(sulphuric acid ester); (2) degraded chitosan formate is dissolved in formamide and heated with oleum/pyridine mixture, the product being recovered as in (1); (3) degraded chondroitin sulphuric acid in formamide is treated with oleum while cooling and the product recovered as in (1); (4) partially degraded laevan and (5) partially degraded starch are similarly sulphated; (6) chitosan, synthesized from chitin by treatment with fused alkali, is dissolved in formic acid and the formate is precipitated with acetone and degraded as in (1), then heated with pyridine-(sulphur trioxide) and the product is recovered as in (1); (7) chondroitin sulphuric acid is further sulphated with pyridine-(sulphur trioxide) in formamide solution; (8) inulin is sulphated in a similar manner; (9) dextran is dissolved in formamide and treated with a formamide solution of pyridine-(sulphur trioxide); (11) potato starch, (12) sodium alginate, (13) laevan and (14) pectin are sulphated with pyridine-(sulphur trioxide) in formamide as above. Specifications 704,516 and 771,138 are referred to.ALSO:Poly-(sulphuric acid esters) of cellulose or cellulose derivatives are produced by treating cellulose or a cellulose derivative with oleum at 0-25 DEG  C., with oleum/pyridine mixture at elevated temperature, or with pyridine-(sulphur trioxide) at 30-110 DEG  C., in the presence of formamide as a solvent.  The product may be precipitated with a water-miscible precipitating agent such as methanol, taken up in water, and the solution adjusted to pH 9 with sodium hydroxide, giving the sodium salt. The latter may be converted to an alkaloid salt for further purification and then reconverted to the sodium salt.  In order to modify the physical properties of the product, a degradation step, e.g. with hydrogen peroxide, acids or alkalies, may be introduced before or after the sulphation.  The degraded material may be fractionated before or after sulphation by fractional precipitation or fractional dissolution.  In an example, carboxy-cellulose is dissolved in formamide and heated with pyridine-(sulphur trioxide) for 2 hours at 85 DEG  C.; the product is precipitated with methanol, taken up in water and converted to the sodium salt, which is further purified by forming the narcotine salt, reconverted to the sodium salt and acidified to give carboxy-cellulose poly-(sulphuric acid ester).