Ono-4007
Ono-4007单钠盐 苯并-1,3-二氧戊环-4-甲酸甲酯 Chemical Name: 2-Deoxy-3-O-(9-phenylnonanoyl)-2-[3(S)-(9-phenylnonanoyloxy)tetradecanamido]-4-O-sulfo-D-glucopyranose monosodium salt
CAS No. 152646-95-2, 111250-67-0 (free acid)
项目整合开发状态: Phase II
项目研究机构: Ono (Originator)
合成路线:2) The acylation of the amine group of benzyl 2-amino-2-deoxy-4,6-O-isopropylidene-beta-D-glucopyranoside (IX) with 3(S)-hydroxytetradecanoic acid (II) by means of pivaloyl chloride in THF gives the corresponding amide (X),which is acylated with 9-phenylnonanoic acid (IV),2-chloro-1-methylpyridinium iodide (CMPI) and dimethylaminopyridine to yield the fully esterified compound (XI).Elimination of the isopropylidene group of (XI) with acetic acid/water affords the dihydroxy compound (XII),which is treated with tert-butyldimethylsilyl chloride and DMAP to give (XIII) with the primary OH-group protected with a TBDMS group.Elimination of the benzyl protecting group of (XIII) by hydrogenation as before gives 2-deoxy-6-O-(tert-butyldimethylsilyl)-3-O-(9-phenylnonanoyl)-2-[3(S)-(9-phenylnonanoyloxy)tetradecanamido]-D-glucopyranose (XIV),which is sulfonated with SO3/pyridine complex in pyridine yielding the 4-O-sulfonated compound (XV).Finally,this compound is desilylated by means of acetic acid in methanol.
📌 参考资料/链接：
参考文献标题:Novel glucopyranose derivs
文献作者:Toda,M.; Shimoji,K.; Sasaki,Y.(Ono Pharmaceutical Co.,Ltd.)
参考来源:EP 0226381; JP 1988179885
📄 详细内容
合成路线:1) The reaction of benzyl 2-amino-4,6-O-benzylidene-2-deoxy-alpha-D-glucopyranoside (I) with 3(S)-hydroxytetradecanoic acid (II) by means of pivaloyl chloride in THF gives the corresponding amide (III),which is acylated with 9-phenylnonanoic acid (IV),dimethylaminopyridine (DMAP) and triethylamine (or tetramethylurea and oxalyl chloride) yielding the fully esterified compound (V).Elimination of the benzylidene group of (V) with HBF4/NaBF4 and the benzyl group by hydrogenolysis with H2 over Pd/C affords the trihydroxy compound (VI),which is treated with tert-butyldimethylsilyl chloride (TBDMS-Cl) and pyridine to give (VII) with the primary OH-group protected with a TBDMS group.The sulfonation of (VII) with SO3/pyridine complex affords the sulfonated compound (VIII),which is finally desilylated with acetic acid in ethanol.
参考文献标题:Salts of glucopyranose deriv.and its intermediate
文献作者:Imaki,K.; Hashimoto,S.; Wakatsuka,H.(Ono Pharmaceutical Co.,Ltd.)
参考来源:EP 0553786; JP 1994041175; US 5733927
合成路线:1) The reaction of benzyl 2-amino-4,6-O-benzylidene-2-deoxy-alpha-D-glucopyranoside (I) with 3(S)-hydroxytetradecanoic acid (II) by means of pivaloyl chloride in THF gives the corresponding amide (III),which is acylated with 9-phenylnonanoic acid (IV),dimethylaminopyridine (DMAP) and triethylamine (or tetramethylurea and oxalyl chloride) yielding the fully esterified compound (V).Elimination of the benzylidene group of (V) with HBF4/NaBF4 and the benzyl group by hydrogenolysis with H2 over Pd/C affords the trihydroxy compound (VI),which is treated with tert-butyldimethylsilyl chloride (TBDMS-Cl) and pyridine to give (VII) with the primary OH-group protected with a TBDMS group.The sulfonation of (VII) with SO3/pyridine complex affords the sulfonated compound (VIII),which is finally desilylated with acetic acid in ethanol.
参考文献标题:ONO-4007
文献作者:Graul,A.; Martel,A.M.; Castar,J.
参考来源:Drugs Fut 1997,22(8),841
产品链接: CAS No. 152646-95-2›› 产品链接: CAS No.111250-67-0››