1-([(3aR,4R,5S,5aR,10bR,13aR)-3a-Ethyl-9-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0(4,12).0(5,10)]nonadeca-4(12),5,7,9-tetraen-13-yl]-4,5-dihydroxy-8-methoxy-6-methyl-3a,4,5,5a,6,11,12,13a-octahydro-1H-indolizino[8,1-cd]carbazol-5-yl]carbonyl)-1,2-triazadien-2-ium -Drug Synthesis Database

【结构式】

【分子编号】10348

【品名】1-([(3aR,4R,5S,5aR,10bR,13aR)-3a-Ethyl-9-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0(4,12).0(5,10)]nonadeca-4(12),5,7,9-tetraen-13-yl]-4,5-dihydroxy-8-methoxy-6-methyl-3a,4,5,5a,6,11,12,13a-octahydro-1H-indolizino[8,1-cd]carbazol-5-yl]carbonyl)-1,2-triazadien-2-ium

【CA登记号】

【分子式】C₄₃H₅₃N₇O₇

【分子量】779.9368

【元素组成】C 66.22% H 6.85% N 12.57% O 14.36%

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：(III)

This compound can be obtained by two related ways: 1) The reaction of vinblastine (I) with anhydrous hydrazine in hot ethanol gives 4-deacetylvinblastine-23-acid hydrazide (II), which by reaction with HCl and NaNO2 in cool methanol - water is converted into the corresponding azide (III). Finally, this compound is condensed with L-tryptophan ethyl ester (IV) in dichloromethane. 2) The hydrolysis of vinblastine (I) with NaOH in refluxing ethanol gives 4-deacetylvinblastoic acid (V), which is condensed with L-tryptophan ethyl ester (IV) by means of isobutyl chloroformate (VI) and N-ethylmorpholine in DMF to afford the 4-O-(isobutoxycarbonyl) derivative (VII). Finally, this compound is partially hydrolyzed with KOH in ethanol.

参考文献中间体

合成目标

【1】 Trouet, A.B.L.; Hannart, J.A.A.J.; Rao, K.S.B. (OmniChem); Vinblastin-23-oyl amino acid derivs. US 4639456 .
【2】 Hamashima, Y. (Shionogi & Co. Ltd.); 7-Carboxyalkenoylamido-3-cephem-4-carboxylic acid derivs.. EP 0136721; ES 8604602; ES 8605278; ES 8700222; GB 2154580; GB 2198727; JP 1985078987; JP 1985163884; JP 1985246388; US 4634697; US 4748170 .
【3】 Trouet, A.B.L.; Rao, K.S.B.; Hannart, J.A.A. (OmniChem); N-Vinblastinoyl-23) derivs. of amino acids and peptides, their preparation and their therapeutic application. EP 0041935 .
【4】 Atassi, G.; Rao, K.S.P.B.; Collard, M.-P.M.; Trouet, A.; Dejonghe, J.P.C.; Hannart, J.A.; Vinblastin-23-oyl amino acid derivatives: Chemistry, physicochemical data, toxicity, and antitumor activities against P388 and L1210 leukemias. J Med Chem 1985, 28, 8, 1079.
【5】 Castaner, J.; Prous, J.; Vintriptol Mesylate. Drugs Fut 1992, 17, 7, 569.

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)	10346	methyl (3aR,4R,5S,5aR,10bR,13aR)-4-(acetoxy)-3a-ethyl-9-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0(4,12).0(5,10)]nonadeca-4(12),5,7,9-tetraen-13-yl]-5-hydroxy-8-methoxy-6-methyl-3a,4,5,5a,6,11,12,13a-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate	446-86-6	C₄₆H₅₈N₄O₉	详情	详情
(II)	10347	methyl (13S,15S,17S)-13-[(3aR,4R,5S,5aR,10bR,13aR)-3a-ethyl-5-(hydrazinocarbonyl)-4,5-dihydroxy-8-methoxy-6-methyl-3a,4,5,5a,6,11,12,13a-octahydro-1H-indolizino[8,1-cd]carbazol-9-yl]-17-ethyl-17-hydroxy-1,11-diazatetracyclo[13.3.1.0(4,12).0(5,10)]nonadeca-4(12),5,7,9-tetraene-13-carboxylate		C₄₃H₅₆N₆O₇	详情	详情
(III)	10348	1-([(3aR,4R,5S,5aR,10bR,13aR)-3a-Ethyl-9-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0(4,12).0(5,10)]nonadeca-4(12),5,7,9-tetraen-13-yl]-4,5-dihydroxy-8-methoxy-6-methyl-3a,4,5,5a,6,11,12,13a-octahydro-1H-indolizino[8,1-cd]carbazol-5-yl]carbonyl)-1,2-triazadien-2-ium		C₄₃H₅₃N₇O₇	详情	详情
(IV)	10349	ethyl (2S)-2-amino-3-(1H-indol-3-yl)propanoate		C₁₃H₁₆N₂O₂	详情	详情
(V)	10350	(3aR,4R,5S,5aR,10bR,13aR)-3a-Ethyl-9-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0(4,12).0(5,10)]nonadeca-4(12),5,7,9-tetraen-13-yl]-4,5-dihydroxy-8-methoxy-6-methyl-3a,4,5,5a,6,11,12,13a-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylic acid		C₄₃H₅₄N₄O₈	详情	详情
(VI)	13423	1-[(Chlorocarbonyl)oxy]-2-methylpropane; Isobutyl chloroformate;isobutyl carbonochloridate	543-27-1	C₅H₉ClO₂	详情	详情
(VII)	10351	methyl (13S,15S,17S)-13-[(3aR,4R,5S,5aR,10bR,13aR)-5-([[(1S)-2-ethoxy-1-(1H-indol-3-ylmethyl)-2-oxoethyl]amino]carbonyl)-3a-ethyl-5-hydroxy-4-[(isobutoxycarbonyl)oxy]-8-methoxy-6-methyl-3a,4,5,5a,6,11,12,13a-octahydro-1H-indolizino[8,1-cd]carbazol-9-yl]-17-ethyl-17-hydroxy-1,11-diazatetracyclo[13.3.1.0(4,12).0(5,10)]nonadeca-4(12),5,7,9-tetraene-13-carboxylate		C₆₁H₇₆N₆O₁₁	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The condensation of O4-deacetyl-vinblastine carboxazide (I) with diethyl ester (+) of 1-amino-2-methylpropylphosphonic acid (II), in cold methylene chloride, gives (1S)-1-[3-(O4-deacetyl-3-demethoxycarbonylvincaleukoblastinyl) carbonylamino]-2-methylpropylphosphonic acid diethyl ester (III).

参考文献中间体

合成目标

【1】 Bizzari, J.P.; Vinfosiltine Sulfate. Drugs Fut 1991, 16, 9, 822.
【2】 Lavielle, G.; Schaeffer, C.; Hautefaye, P.; Boutin, J.A.; Cudennec, C.A.; Pierré, A.; New alpha-aminophosphonic acid derivatives of vinblastine: Chemistry and antitumor activity. J Med Chem 1991, 34, 7, 1998-2003.

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)	10348	1-([(3aR,4R,5S,5aR,10bR,13aR)-3a-Ethyl-9-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0(4,12).0(5,10)]nonadeca-4(12),5,7,9-tetraen-13-yl]-4,5-dihydroxy-8-methoxy-6-methyl-3a,4,5,5a,6,11,12,13a-octahydro-1H-indolizino[8,1-cd]carbazol-5-yl]carbonyl)-1,2-triazadien-2-ium		C₄₃H₅₃N₇O₇	详情	详情
(II)	14215	diethyl (1S)-1-amino-2-methylpropylphosphonate		C₈H₂₀NO₃P	详情	详情

Extended Information