(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy]-1,9,12-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate -Drug Synthesis Database

【结构式】

【分子编号】10470

【品名】(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy]-1,9,12-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate

【CA登记号】

【分子式】C₄₅H₄₉NO₁₃

【分子量】811.883

【元素组成】C 66.57% H 6.08% N 1.73% O 25.62%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(II)

Two new syntheses of taxol have been described: 1) The oxidative cleavage of 10-deacetyltaxol-7-xyloside (I) with sodium periodate in methanol - chloroform gives 10-deacetyltaxol (II), which is then acetylated with acetic anhydride and pyridine. 2) By deacetylation of 2'-acetyltaxol (III) by means of dimethylamine in aqueous methanol.

参考文献中间体

合成目标

【1】 Rao, K.V. (University of Florida); Process for the preparation of taxol and 10-deacetyltaxol. US 5200534 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	10469	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy]-1,12-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2R,3R,4S,5R)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl]oxy]-6-oxatetracyclo[11.3.1.0(3,10)	C₅₀H₅₇NO₁₇	详情	详情
(II)	10470	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy]-1,9,12-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate	C₄₅H₄₉NO₁₃	详情	详情
(III)	10471	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-2-(acetoxy)-3-(benzoylamino)-3-phenylpropanoyl]oxy]-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate	C₄₉H₅₃NO₁₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IIa)

Several partial syntheses of docetaxel have been described: The selective hydrolysis of Taxol A (I, R = Ph), Taxol B (I, R = C(Me)=CHMe) or Taxol C (I, R = C5H11) with NaHCO3 in THF/water gives the corresponding 10-deacetyl derivatives (II), which by selective silylation with triethylsilyl chloride in pyridine are converted into the 10-deacetyl-2',7-bis(triethylsilyl) compounds (III). The reaction of compounds (III) with zirconocene chloride hydride [bis(cyclopentadienyl)zirconium chloride hydride] in THF afford the corresponding imino derivatives (IV), which, without isolation are hydrolyzed and desilylated by a treatment with concentrated aqueous HCl in ethanol giving 10-deacetyltaxolamine (V). Finally, this compound is acylated at the amino group by a treatment by di-tert-butyl dicarbonate and NaHCO3 in ethyl acetate/water.

参考文献中间体

合成目标

【1】 Young, T.H. (Hauser, Inc.); Preparation of Taxol and docetaxel through primary amines. EP 0852581; WO 9623780 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	14346	di(tert-butyl) malonate; Di-tert-butyl malonate	541-16-2	C₁₁H₂₀O₄	详情	详情
(IIa)	10470	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy]-1,9,12-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₄₅H₄₉NO₁₃	详情	详情
(Ia)	10595	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy]-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate	33069-62-4	C₄₇H₅₁NO₁₄	详情	详情
(Ib)	10731	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,9-dihydroxy-15-[((2R,3S)-2-hydroxy-3-[[(E)-2-methyl-2-butenoyl]amino]-3-phenylpropanoyl)oxy]-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₄₅H₅₃NO₁₄	详情	详情
(IIIa)	12495	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-([(2R,3S)-3-(benzoylamino)-3-phenyl-2-[(triethylsilyl)oxy]propanoyl]oxy)-1,12-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₅₇H₇₇NO₁₃Si₂	详情	详情
(IVa)	12496	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,12-dihydroxy-10,14,17,17-tetramethyl-11-oxo-15-([(2R,3S)-3-phenyl-3-[[(E)-benzylidene]amino]-2-[(triethylsilyl)oxy]propanoyl]oxy)-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₅₇H₇₇NO₁₂Si₂	详情	详情
(Ic)	28490	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-([(2R,3S)-3-[(cyclopentylcarbonyl)amino]-2-hydroxy-3-phenylpropanoyl]oxy)-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₄₆H₅₅NO₁₄	详情	详情
(IIb)	28491	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,9,12-trihydroxy-15-[((2R,3S)-2-hydroxy-3-[[(Z)-2-methyl-2-butenoyl]amino]-3-phenylpropanoyl)oxy]-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₄₃H₅₁NO₁₃	详情	详情
(IIc)	28492	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-([(2R,3S)-3-[(cyclopentylcarbonyl)amino]-2-hydroxy-3-phenylpropanoyl]oxy)-1,9,12-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₄₄H₅₃NO₁₃	详情	详情
(IIIb)	28493	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,12-dihydroxy-10,14,17,17-tetramethyl-15-([(2R,3S)-3-[[(Z)-2-methyl-2-butenoyl]amino]-3-phenyl-2-[(triethylsilyl)oxy]propanoyl]oxy)-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₅₅H₇₉NO₁₃Si₂	详情	详情
(IIIc)	28494	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-([(2R,3S)-3-[(cyclopentylcarbonyl)amino]-3-phenyl-2-[(triethylsilyl)oxy]propanoyl]oxy)-1,12-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₅₆H₈₁NO₁₃Si₂	详情	详情
(IVb)	28495	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,12-dihydroxy-10,14,17,17-tetramethyl-15-([(2R,3S)-3-[[(E,2Z)-2-methyl-2-butenylidene]amino]-3-phenyl-2-[(triethylsilyl)oxy]propanoyl]oxy)-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₅₅H₇₉NO₁₂Si₂	详情	详情
(IVc)	28496	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-([(2R,3S)-3-[[(E)-cyclopentylmethylidene]amino]-3-phenyl-2-[(triethylsilyl)oxy]propanoyl]oxy)-1,12-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₅₆H₈₁NO₁₂Si₂	详情	详情
(V)	12497	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-[[(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl]oxy]-1,9,12-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₃₈H₄₅NO₁₂	详情	详情

Extended Information