-Drug Synthesis Database

【结构式】

【药物名称】

【化学名称】2(S)-Hydroxy-4-oxo-4-(paclitaxel-2'-O-yl)butyric acid sodium salt
　　　　　　[2aR,4S,4aS,6R,9S(2R,3S),11S,12S,12aR,12bS]-3-Benzamido-2-[4-carboxy-3(S)-hydroxypropanoyloxy]-3-phenylpropionic acid 6,12b-diacetoxy-12-(benzoyloxy)-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benz[1,2-b]oxet-9-yl ester sodium salt

【CA登记号】

【分子式】C₅₁H₅₄NNaO₁₈

【分子量】991.98473

【开发单位】Pharmachemie (Originator)

【药理作用】Chemical Delivery Systems, DRUG DELIVERY, Drug Delivery Systems, ONCOLYTIC DRUGS, Antimitotic Drugs, Microtubule-Stabilizing Agents, Taxanes

合成路线1

Malic acid (I) was protected as the 1,2-O-isopropylidene derivative (II) upon treatment with acetone in the presence of acid catalyst. Condensation of (II) with paclitaxel (III) using diisopropylcarbodiimide and DMAP produced the 2'-ester (IV). After hydrolytic cleavage of the isopropylidene protecting group of (IV), conversion to the corresponding sodium carboxylate salt furnished the title compound.

参考文献中间体

【1】 Braamer, L.; Damen, E.W.P.; Wiegerinck, P.H.G.; Sperling, D.; de Vos, D.; Scheren, H.W.; Paclitaxel esters of malic acid as prodrugs with improved water solubility. Bioorg Med Chem 2000, 8, 2, 427.
【2】 Wiegerinck, P.H.G.; Scheeren, J.W.; Damen, E.W.P.; Sperling, D.; Braamer, L.; De Vos, D. (Pharmachemie BV); Water soluble analogs and prodrugs of paclitaxel. WO 0010988 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	11058	(S)-(+)-Hydroxysuccinic acid; (S)-(+)-Malic acid; (S)-(+)-2-Hydroxybutanedioic acid; L-(-)-Apple acid	97-67-6	C₄H₆O₅	详情	详情
(II)	39221	2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]acetic acid	73991-95-4	C₇H₁₀O₅	详情	详情
(III)	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
(IV)	39222	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-([2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]acetyl]oxy)-3-phenylpropanoyl]oxy]-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]		C₅₄H₅₉NO₁₈	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)