SEMISYNTHETIC HEPARINS WITH 2-DEOXY-2-SULFAMINO-ALPHA-L-IDURONIC ACIDRESIDUES - CHEMICAL-REACTIVITY AND BIOLOGICAL-ACTIVITY

Ammonolysis of the epoxide rings of 2,3-anhydro-alpha-L-guluronic acid residues, generated in alkaline medium from 2-O-sulfated alpha-L-idur onic acid residues of heparin quantitatively afforded 2-amino-2-deoxy- alpha-L-iduronic acid residues. N-sulfation of these residues by TMA . SO3 complex led to a formal replacement of the original 2-O-sulfate g roups of heparin with N-sulfates, without configurational changes. The se modified uronic acid residues (no longer amenable to alkaline epoxi dation) can be easily N-desulfated. The presence of negative or positi ve charges at position 2 of the newly generated 2-amino-2-deoxy-alpha- L-iduronic acid residues influences the in vivo antithrombotic activit y and haemorrhagic effects in different ways. A free amino group mainl y decreases the haemorrhagic properties of heparin, while a negatively charged N-sulfate group decreases the coagulation parameters.