SanOrg-123781, SR-123781A

Chemical Name: Methyl O-2,3,4,6-tetra-O-sulfo-alpha-D-glucopyranosyl-(1--4)-O-2,3,6-tri-O-sulfo-alpha-D-glucopyranosyl-(1--4)-O-2,3,6-tri-O-sulfo-beta-D-glucopyranosyl-(1--4)-O-2,3-di-O-methyl-6-O-sulfo-alpha-D-glucoyranosyl-(1--4)-[O-2,3,6-tri-O-methyl-beta-D-glucopyranosyl-(1--4)-O-2,3,6-tri-O-methyl-alpha-D-glucopyranosyl-(1--4)]3-O-2,3,6-tri-O-methyl-beta-D-glucopyranosyl-(1--4)-O-2,3-di-O-methyl-6-O-sulfo-alpha-D-glucopyranosyl-(1--4)-O-2,3-di-O-methyl-beta-D-glucopyranurosyl-(1--4)-O-2,3,6-tri-O-sulfo-alpha-D-glucopyranosyl-(1--4)-O-2,3-di-O-methyl-alpha-L-idopyranurosyl]-(1--4)-3-O-methyl-alpha-D-glucopyranoside bis(hydrogen sulfate) nonadecasodium salt
CAS No. 232602-93-6
项目整合开发状态: Phase I
项目研究机构: Sanofi-Aventis (Originator), Organon (Codevelopment)
合成路线:The intermediate thioglycoside (V) is prepared as follows.Esterification of maltotriose (I) with acetic anhydride and sodium acetate provides peracetate (II).Subsequent reaction of (II) with ethanethiol in the presence of boron trifluoride etherate yields the ethyl thiopyranoside (III).Removal of the acetate esters of (III) is effected by methanolysis in the presence of potassium tert-butoxide,yielding (IV).Then,reesterification of (IV) by means of benzoyl chloride and pyridine furnishes the target intermediate (V).

合成路线:The known disaccharide thioglucoside (VI) is esterified by means of benzoyl chloride and pyridine to give the penta-benzoate (VII).Coupling between thioglycoside (VII) and 2,3-di-O-methyl-1,6-anhydro-D-glucose (VIII) is effected by treatment with N-iodosuccinimide and trifluoromethanesulfonic acid,yielding trisaccharide (IX).After methanolysis of the benzoate esters,the resultant penta-hydroxy compound (X) is alkylated with iodomethane and NaH,leading to the corresponding methyl ether (XI).Hydrolysis of the benzylidene acetal of (XI) with 80% AcOH provides diol (XII).The primary hydroxyl group of (XII) is then selectively esterified by using 1-(benzoyloxy)-benzotriazole to produce the mono-benzoate (XIII).

合成路线:Coupling between trisaccharide (XIII) and thioglycoside (VII) using N-iodosuccinimide/trifluoromethanesulfonic acid furnishes pentasaccharide (XIV).After methanolysis of the benzoate esters of (XIV),the poly-methyl ether (XV) is prepared by methylation of (XIV) with iodomethane and NaH.Acidic hydrolysis of the benzylidene acetal (XV),followed by selective esterification with 1-(benzoyloxy)-benzotriazole affords benzoate (XVI).

合成路线:A new coupling of pentasaccharide (XVI) with thioglycoside (VII) produces heptasaccharide (XVII).Hydrolysis of the benzoate esters of (XVII),followed by O-methylation,yields methyl ether (XVIII).

合成路线:After acidic hydrolysis of the benzylidene acetal of (XVIII),esterification with 1-(benzoyloxy)-benzotriazole leads to (XIX).This is then coupled with a third moiety of disaccharide thioglycoside (VII),producing (XX).

合成路线:The nonasaccharide (XX) is transformed into (XXI) by the sequence of benzoate esters hydrolysis,O-methylation,acetal hydrolysis,and selective mono-benzoylation,following the same methods as above.The free hydroxyl group of (XXI) is subsequently protected by esterification with levulinic acid (XXII) to give levulinate ester (XXIII).Opening of the 1,6-anhydroglucose unit of (XXIII) is then accomplished by treatment with acetic anhydride in the presence of acetic acid and trifluoroacetic acid,producing (XXIV).