【药物名称】Ono-4007
化学结构式(Chemical Structure):
参考文献No.6481
标题:Novel glucopyranose derivs
作者:Toda, M.; Shimoji, K.; Sasaki, Y. (Ono Pharmaceutical Co., Ltd.)
来源:EP 0226381; JP 1988179885
合成路线图解说明:

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.

参考文献No.21590
标题:Salts of glucopyranose deriv. and its intermediate
作者:Imaki, K.; Hashimoto, S.; Wakatsuka, H. (Ono Pharmaceutical Co., Ltd.)
来源:EP 0553786; JP 1994041175; US 5733927
合成路线图解说明:

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No.416897
标题:ONO-4007
作者:Graul, A.; Martel, A.M.; Casta馿r, J.
来源:Drugs Fut 1997,22(8),841
合成路线图解说明:

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.

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