N-{[(2S)-4-ethyl-2,3-dihydro-2-furanyl]methyl}-2,4-dinitrobenzenesulfonamide -Drug Synthesis Database

【结构式】

【分子编号】63759

【品名】N-{[(2S)-4-ethyl-2,3-dihydro-2-furanyl]methyl}-2,4-dinitrobenzenesulfonamide

【CA登记号】

【分子式】C₁₃H₁₅N₃O₇S

【分子量】357.34412

【元素组成】C 43.7% H 4.23% N 11.76% O 31.34% S 8.97%

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：(VIII)

A stereocontrolled total synthesis of vinblastine has been reported. 3-Ethyl-5-phenyl-4-pentenal (I) is transformed into cyanohydrin (II), which is further acetylated with Ac2O in pyridine to furnish the racemic alpha-acetoxy nitrile (III). Enzymatic hydrolysis of cyanohydrin acetate (III) leads to (S)-cyanohydrin (IV) as a mixture of diastereomers at the 4-ethyl group. Ozonolysis of (IV) produces the cyclic hemiacetal (V), which is subsequently dehydrated to the dihydrofuran (VI) employing mesyl chloride and triethylamine. The cyano group of (VI) is then reduced to the primary amine (VII) with LiAlH4 in THF. Acylation of amine (VII) with 2,4-dinitrobenzenesulfonyl chloride leads to the corresponding sulfonamide (VIII) (8).

参考文献中间体

合成目标

【1】 Yokoshima, S.; Ueda, T.; Kobayashi, S.; Sato, A.; Kuboyama, T.; Tokuyama, H.; Fukuyama, T.; Stereocontrolled total synthesis of (+)-vinblastine. J Am Chem Soc 2002, 124, 10, 2137.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	63644	(E)-3-ethyl-5-phenyl-4-pentenal	C₁₃H₁₆O	详情	详情
(II)	63645	(E)-4-ethyl-2-hydroxy-6-phenyl-5-hexenenitrile	C₁₄H₁₇NO	详情	详情
(III)	63646	(E)-1-cyano-3-ethyl-5-phenyl-4-pentenyl acetate	C₁₆H₁₉NO₂	详情	详情
(IV)	63647		C₁₄H₁₇NO	详情	详情
(V)	63648	(2S)-4-ethyl-5-hydroxytetrahydro-2-furancarbonitrile	C₇H₁₁NO₂	详情	详情
(VI)	63757	(2S)-4-ethyl-2,3-dihydro-2-furancarbonitrile	C₇H₉NO	详情	详情
(VII)	63758	[(2S)-4-ethyl-2,3-dihydro-2-furanyl]methanamine; [(2S)-4-ethyl-2,3-dihydro-2-furanyl]methylamine	C₇H₁₃NO	详情	详情
(VIII)	63759	N-{[(2S)-4-ethyl-2,3-dihydro-2-furanyl]methyl}-2,4-dinitrobenzenesulfonamide	C₁₃H₁₅N₃O₇S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

Mitsunobu coupling between tryptophol (XVII) and sulfonamide (VIII) yields the N-sulfonyl tryptamine derivative (XVIII). Hydration of the cyclic enol ether, with simultaneous Boc group cleavage under acidic conditions affords lactol (XIX). Subsequent deprotection of the dinitrobenzenesulfonyl group of (XIX) with piperidine in MeOH proceeds with rearrangement of the deprotected amino lactol to the cyclic hydroxy enamine (XX). This, upon further heating, undergoes a Diels-Alder type reaction to afford the pentacyclic vindoline ring system (XXI). Following a previously reported synthetic pathway for (XXI), regioselective elimination of the secondary alcohol function, followed by protective group exchange at the phenolic hydroxyl, and oxidation with benzeneseleninic anhydride leads to the C4-alcohol (XXII). Further introduction of the C3-hydroxyl with m chloroperbenzoic acid, and reduction of the resultant imine with NaBH3CN provides diol (XXIII). After reductive methylation of the indoline N of (XXIII) with HCHO/NaBH3CN, acetylation of the secondary hydroxyl group produces ( ) vindoline (XXIII) (8, 9).

参考文献中间体

合成目标

【1】 Schneider, C.; First de novo synthesis of the bisindole alkaloid vinblastine. Angew Chem. Int Ed 2002, 41, 22, 4217.
【2】 Yokoshima, S.; Ueda, T.; Kobayashi, S.; Sato, A.; Kuboyama, T.; Tokuyama, H.; Fukuyama, T.; Stereocontrolled total synthesis of (+)-vinblastine. J Am Chem Soc 2002, 124, 10, 2137.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VIII)	63759	N-{[(2S)-4-ethyl-2,3-dihydro-2-furanyl]methyl}-2,4-dinitrobenzenesulfonamide	C₁₃H₁₅N₃O₇S	详情	详情
(XVII)	63768	tert-butyl 3-(2-hydroxyethyl)-2-[1-(methoxycarbonyl)vinyl]-6-[(methylsulfonyl)oxy]-1H-indole-1-carboxylate	C₂₀H₂₅NO₈S	详情	详情
(XVIII)	63769	tert-butyl 3-[2-([(2,4-dinitrophenyl)sulfonyl]{[(2S)-4-ethyl-2,3-dihydro-2-furanyl]methyl}amino)ethyl]-2-[1-(methoxycarbonyl)vinyl]-6-[(methylsulfonyl)oxy]-1H-indole-1-carboxylate	C₃₃H₃₈N₄O₁₄S₂	详情	详情
(XIX)	63770	methyl 2-{3-[2-([(2,4-dinitrophenyl)sulfonyl]{[(2S)-4-ethyl-5-hydroxytetrahydro-2-furanyl]methyl}amino)ethyl]-6-[(methylsulfonyl)oxy]-1H-indol-2-yl}acrylate	C₂₈H₃₂N₄O₁₃S₂	详情	详情
(XX)	63771	methyl 2-{3-{2-[(3S)-5-ethyl-3-hydroxy-3,4-dihydro-1(2H)-pyridinyl]ethyl}-6-[(methylsulfonyl)oxy]-1H-indol-2-yl}acrylate	C₂₂H₂₈N₂O₆S	详情	详情
(XXI)	63772	methyl (2S,3aR,10bR,13aS)-3a-ethyl-2-hydroxy-8-[(methylsulfonyl)oxy]-2,3,3a,4,6,11,12,13a-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate	C₂₂H₂₈N₂O₆S	详情	详情
(XXII)	63773	methyl (3aR,4R,10bR,13aR)-3a-ethyl-4-hydroxy-8-methoxy-3a,4,6,11,12,13a-hexahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate	C₂₂H₂₆N₂O₄	详情	详情
(XXIII)	63774	methyl (3aR,4R,5S,5aR,10bS,13aR)-3a-ethyl-4,5-dihydroxy-8-methoxy-3a,4,5,5a,6,11,12,13a-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate	C₂₂H₂₈N₂O₅	详情	详情
(XXIV)	63596	methyl 4-(acetyloxy)-3a-ethyl-5-hydroxy-6-methyl-8-(methyloxy)-3a,4,5,5a,6,11,12,13a-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate	C₂₅H₃₂N₂O₆	详情	详情

Extended Information