Synthesis of laminarin sulfates with anticoagulant activity

Laminarin sulfates were synthesized without significant degradation of the genuine laminarin chain using SO3/pyridine complex as a sulfation reagent. 6 derivatives with a degree of sulfation (d.s.) ranging from 0.30 to 2.26 could be obtained. According to methylation analysis the C-6-OH-groups of the glucose molecules were preferentially substituted, followed by the OH-groups at C-2 and C-4. The derivatives Lam S1 (d.s. = 0.30) and Lam S2 (d.s. = 0.64) showed no activity in the blood coagulation tests. With increasing d.s. the anticoagulant activity increased until an optimum d.s. of 1.49. Anticoagulant laminarin sulfates showed significant activity in the activated partial thromboplastin time (APTT) test but were less active in the anti-Factor Xa as well as anti-Factor IIa assay. Therefore, the anticoagulant activity of the synthesized laminarin sulfates is due to the interaction at an early stage of the coagulation cascade and neither to a direct inhibition of Factor Xa and IIa nor to an indirect effect mediated by antithrombin III.