methyl (2R,8S)-8-(bromomethyl)-4-hydroxy-2-methyl-1-oxo-6-[(5,6,7-trimethoxy-1H-indol-2-yl)carbonyl]-1,2,3,6,7,8-hexahydropyrrolo[3,2-e]indole-2-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】33739

【品名】methyl (2R,8S)-8-(bromomethyl)-4-hydroxy-2-methyl-1-oxo-6-[(5,6,7-trimethoxy-1H-indol-2-yl)carbonyl]-1,2,3,6,7,8-hexahydropyrrolo[3,2-e]indole-2-carboxylate

【CA登记号】

【分子式】C₂₆H₂₆BrN₃O₈

【分子量】588.41186

【元素组成】C 53.07% H 4.45% Br 13.58% N 7.14% O 21.75%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(I)

Protection of the phenolic group of duocarmycin B2 (I) with tert-butyldimethylsilyl chloride and imidazole afforded silyl ether (II). The methyl ester group of (III) was then converted to either allyl ester (III) or benzyl ester (IV) upon treatment with the respective alcohols and K2CO3 at 0 C. Reduction of (III) or (IV) with NaBH4 in allyl alcohol provided the 3alpha-hydroxy compounds (V) and (VI). Subsequent BF3-catalyzed Wagner-Meerwein type rearrangement in (V) or (VI) produced the indole-3-carboxylates (VII) and (VIII). Carboxylic acid (IX) was then obtained by deprotection of the allyl group of (VII) using Pd(PPh3)4/dimedone or the benzyl group of (VIII) using Pd/C in the presence of ammonium formate.

参考文献中间体

合成目标

【1】 Saito, H.; Konayashi, E.; Gomi, K.; Asai, A.; Nagamura, S.; Kanda, Y.; Wagner-Meerwein rearangement of duocarmycins. Chem Pharm Bull 1996, 44, 5, 933-939.
【2】 Okabe, M.; Tamaoki, T.; Saito, H.; Okamoto, A.; Amishiro, N.; Murakata, C.; Synthesis and antitumor activity of duocarmycin derivatives: Modification of segment-A of A-ring pyrrole compounds. J Med Chem 1999, 42, 15, 2946-60.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	33739	methyl (2R,8S)-8-(bromomethyl)-4-hydroxy-2-methyl-1-oxo-6-[(5,6,7-trimethoxy-1H-indol-2-yl)carbonyl]-1,2,3,6,7,8-hexahydropyrrolo[3,2-e]indole-2-carboxylate	C₂₆H₂₆BrN₃O₈	详情	详情
(II)	33740	methyl (2R,8S)-8-(bromomethyl)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-1-oxo-6-[(5,6,7-trimethoxy-1H-indol-2-yl)carbonyl]-1,2,3,6,7,8-hexahydropyrrolo[3,2-e]indole-2-carboxylate	C₃₂H₄₀BrN₃O₈Si	详情	详情
(III)	33741	allyl (2R,8S)-8-(bromomethyl)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-1-oxo-6-[(5,6,7-trimethoxy-1H-indol-2-yl)carbonyl]-1,2,3,6,7,8-hexahydropyrrolo[3,2-e]indole-2-carboxylate	C₃₄H₄₂BrN₃O₈Si	详情	详情
(IV)	33742	benzyl (2R,8S)-8-(bromomethyl)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-1-oxo-6-[(5,6,7-trimethoxy-1H-indol-2-yl)carbonyl]-1,2,3,6,7,8-hexahydropyrrolo[3,2-e]indole-2-carboxylate	C₃₈H₄₄BrN₃O₈Si	详情	详情
(V)	33743	allyl (1R,2R,8S)-8-(bromomethyl)-4-[[tert-butyl(dimethyl)silyl]oxy]-1-hydroxy-2-methyl-6-[(5,6,7-trimethoxy-1H-indol-2-yl)carbonyl]-1,2,3,6,7,8-hexahydropyrrolo[3,2-e]indole-2-carboxylate	C₃₄H₄₄BrN₃O₈Si	详情	详情
(VI)	33744	benzyl (1R,2R,8S)-8-(bromomethyl)-4-[[tert-butyl(dimethyl)silyl]oxy]-1-hydroxy-2-methyl-6-[(5,6,7-trimethoxy-1H-indol-2-yl)carbonyl]-1,2,3,6,7,8-hexahydropyrrolo[3,2-e]indole-2-carboxylate	C₃₈H₄₆BrN₃O₈Si	详情	详情
(VII)	33745	allyl (8S)-8-(bromomethyl)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-6-[(5,6,7-trimethoxy-1H-indol-2-yl)carbonyl]-3,6,7,8-tetrahydropyrrolo[3,2-e]indole-1-carboxylate	C₃₄H₄₂BrN₃O₇Si	详情	详情
(VIII)	33746	benzyl (8S)-8-(bromomethyl)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-6-[(5,6,7-trimethoxy-1H-indol-2-yl)carbonyl]-3,6,7,8-tetrahydropyrrolo[3,2-e]indole-1-carboxylate	C₃₈H₄₄BrN₃O₇Si	详情	详情
(IX)	33747	(8S)-8-(bromomethyl)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-6-[(5,6,7-trimethoxy-1H-indol-2-yl)carbonyl]-3,6,7,8-tetrahydropyrrolo[3,2-e]indole-1-carboxylic acid	C₃₁H₃₈BrN₃O₇Si	详情	详情

Extended Information