IDN-5390, -Drug Synthesis Database

【结构式】

【药物名称】IDN-5390

【化学名称】2-O-Acetyl-1,3-anhydro-2-C-[(1S,2S,3R,9S)-2-(benzoyloxy)-9-[3(S)-(tert-butoxycarboxamido)-2(R)-hydroxy-5-methylhexanoyloxy]-1,5-dihydroxy-4,8,11,11-tetramethyl-6-oxobicyclo[5.3.1]undeca-4,7-dien-3-yl]-4-deoxy-D-erythro-pentitol
　　　　　　Benzoic acid (1S,2S,3R,9S)-3-[(2R,3S)-3-(acetoxy)-2-(2-hydroxyethyl)-3-oxetanyl]-9-[(2R,3S)-3-(tert-butoxycarbonylamino)-2-hydroxy-5-methylhexanoyloxy]-1,5-dihydroxy-4,8,11,11-tetramethyl-6-oxobicyclo[5.3.1]undeca-4,7-dien-2-yl ester

【CA登记号】191276-31-0

【分子式】C₄₁H₅₇NO₁₄

【分子量】787.90974

【开发单位】Indena (Originator), Ist. di Ricerche Farmacol. Mario Negri (Codevelopment)

【药理作用】Oncolytic Drugs, Angiogenesis Inhibitors, Antimitotic Drugs, Microtubule-Stabilizing Agents, Taxanes

合成路线1

Oxidation of 10-deacetylbaccatin III (I) by means of cupric acetate yielded diketone (II), in equilibrium with the retroaldol product (III). Subsequent reduction employing NaBH4 and CeCl3 produced the seco-taxane (IV) as the major reaction product. Selective protection of the 7 and 9 hydroxyl groups was achieved by treatment with chlorotriethylsilane and imidazole. The resultant 7,9-disilylated derivative (V) was then acylated by the oxazolidinecarboxylic acid (VI) to furnish, after acidic hydrolysis, the title C-seco taxane derivative.

参考文献中间体

【1】 Appendino, G.; et al.; Synthesis and evaluation of C-seco paclitaxel analogues. Tetrahedron Lett 1997, 38, 24, 4273.

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)	10467	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,9,12,15-tetrahydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate	32981-86-5	C₂₉H₃₆O₁₀	详情	详情
(II)	54790	(1S,2S,3R,4S,7R,10S,15S)-4-(acetyloxy)-1,9,15-trihydroxy-10,14,17,17-tetramethyl-11,12-dioxo-6-oxatetracyclo[11.3.1.0~3,10~.0~4,7~]heptadec-13-en-2-yl benzoate		C₂₉H₃₄O₁₀	详情	详情
(III)	54791	(1S,2S,3R,9S)-3-[(2R,3S)-3-(acetyloxy)-2-(2-oxoethyl)oxetanyl]-1,5,9-trihydroxy-4,8,11,11-tetramethyl-6-oxobicyclo[5.3.1]undeca-4,7-dien-2-yl benzoate		C₂₉H₃₄O₁₀	详情	详情
(IV)	54792	(1S,2S,3R,9S)-3-[(2R,3S)-3-(acetyloxy)-2-(2-hydroxyethyl)oxetanyl]-1,5,9-trihydroxy-4,8,11,11-tetramethyl-6-oxobicyclo[5.3.1]undeca-4,7-dien-2-yl benzoate		C₂₉H₃₆O₁₀	详情	详情
(V)	54793	(1S,2S,3R,9S)-3-((2R,3S)-3-(acetyloxy)-2-{2-[(triethylsilyl)oxy]ethyl}oxetanyl)-1,9-dihydroxy-4,8,11,11-tetramethyl-6-oxo-5-[(triethylsilyl)oxy]bicyclo[5.3.1]undeca-4,7-dien-2-yl benzoate		C₄₁H₆₄O₁₀Si₂	详情	详情
(VI)	54794	(4S,5R)-3-(tert-butoxycarbonyl)-4-isobutyl-2-phenyl-1,3-oxazolidine-5-carboxylic acid		C₁₉H₂₇NO₅	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)