AT-2433 B1, -Drug Synthesis Database

【结构式】

【药物名称】AT-2433 B1

【化学名称】13-[6-O-[2,4-Dideoxy-4-(methylamino)-alpha-L-threo-pentofuranosyl]-4-O-methyl-beta-D-glucopyranosyl]-6-methyl-6,7,12,13-tetrahydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione

【CA登记号】102622-96-8

【分子式】C₃₄H₃₆N₄O₉

【分子量】644.68742

【开发单位】Schering-Plough (Originator)

【药理作用】Antibiotics and Alkaloids, Antineoplastic Antibiotics, ONCOLYTIC DRUGS

合成路线1 合成路线2

合成路线1

The cyclization of 3,4-bis(3-indolyl)-1-methylpyrroline-2,5-dione (I) by hydrogenation with H2 over Pd/C in DMF, followed by a treatment with TFA, gives the hexacyclic dione (II), which then is condensed with aminosugar (III) in refluxing methanol and dehydrogenated with DDQ in THF to afford the target glycoside.

参考文献中间体

【1】 Van Vranken, D.L.; Chisholm, J.D.; Regiocontrolled synthesis of the antitumor antibiotic AT2433-A1. J Org Chem 2000, 65, 22, 7541.
【2】 Chisholm, J.D.; et al.; A caveat in the application of the excition chirality method to N, N-dialkyl amides. Synthesis and structural revision of AT2433-B1. J Am Chem Soc 1999, 121, 15, 3801.

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)	41012	3,4-di(1H-indol-3-yl)-1-methyl-1H-pyrrole-2,5-dione	113963-68-1	C₂₁H₁₅N₃O₂	详情	详情
(II)	45598	(4bS,4cS,7aS,12bR)-6-methyl-7a,12,12b,13-tetrahydro-4bH-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(4cH,6H)-dione		C₂₁H₁₇N₃O₂	详情	详情
(III)	45599	(3R,4R,5S,6R)-6-([[(2S,4S,5S)-4-hydroxy-5-(methylamino)tetrahydro-2H-pyran-2-yl]oxy]methyl)-5-methoxytetrahydro-2H-pyran-2,3,4-triol		C₁₃H₂₅NO₈	详情	详情

合成路线2

The intermediate aminosugar (III) has been obtained as follows: The protection of the alcohol (IV) with Bn-Br and NaH in DMF gives the benzyl ether (V), which is oxidized with OsO4 and NaIO4 in acetone/THF to yield the aldehyde (VI). The cyclization of (VI) by means of TsOH in dioxane/water affords the lactol (VII), which is treated with diethylamino sulfurtrifluoride (DAST) to provide the glycosyl fluoride (VIII). The condensation of (VIII) with the benzylated glucose derivative (IX) by means of AgClO4 and SnCl2 in THF/ethyl ether gives the disaccharide (X). The reduction of the carbamoyl group of (X) with LiAlH4 in refluxing THF yields the methylamino derivative (XI), which is finally debenzylated by hydrogenation over Pd/C in ethanol/THF to afford the target aminosugar (III).

参考文献中间体

【1】 Van Vranken, D.L.; Chisholm, J.D.; Regiocontrolled synthesis of the antitumor antibiotic AT2433-A1. J Org Chem 2000, 65, 22, 7541.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(III)	45599	(3R,4R,5S,6R)-6-([[(2S,4S,5S)-4-hydroxy-5-(methylamino)tetrahydro-2H-pyran-2-yl]oxy]methyl)-5-methoxytetrahydro-2H-pyran-2,3,4-triol		C₁₃H₂₅NO₈	详情	详情
(IV)	45589	tert-butyl (4S)-4-(1-hydroxy-3-butenyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate		C₁₄H₂₅NO₄	详情	详情
(V)	45590	tert-butyl (4S)-4-[1-(benzyloxy)-3-butenyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate	15930-53-7	C₂₁H₃₁NO₄	详情	详情
(VI)	45591	tert-butyl (4S)-4-[1-(benzyloxy)-3-oxopropyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate		C₂₀H₂₉NO₅	详情	详情
(VII)	45592	tert-butyl (3S,4S)-4-(benzyloxy)-6-hydroxytetrahydro-2H-pyran-3-ylcarbamate		C₁₇H₂₅NO₅	详情	详情
(VIII)	45593	tert-butyl (3S,4S)-4-(benzyloxy)-6-fluorotetrahydro-2H-pyran-3-ylcarbamate		C₁₇H₂₄FNO₄	详情	详情
(IX)	45594	[(2R,3S,4S,5R,6R)-4,5,6-tris(benzyloxy)-3-methoxytetrahydro-2H-pyran-2-yl]methanol		C₂₈H₃₂O₆	详情	详情
(X)	45595	tert-butyl (3S,4S,6S)-4-(benzyloxy)-6-[[(2R,3S,4S,5R,6R)-4,5,6-tris(benzyloxy)-3-methoxytetrahydro-2H-pyran-2-yl]methoxy]tetrahydro-2H-pyran-3-ylcarbamate		C₄₅H₅₅NO₁₀	详情	详情
(XI)	45596	N-((3S,4S,6S)-4-(benzyloxy)-6-[[(2R,3S,4S,5R,6R)-4,5,6-tris(benzyloxy)-3-methoxytetrahydro-2H-pyran-2-yl]methoxy]tetrahydro-2H-pyran-3-yl)-N-methylamine; (3S,4S,6S)-4-(benzyloxy)-N-methyl-6-[[(2R,3S,4S,5R,6R)-4,5,6-tris(benzyloxy)-3-methoxytetrahydro-2H-pyran-2-yl]methoxy]tetrahydro-2H-pyran-3-amine		C₄₁H₄₉NO₈	详情	详情

Extended Information