(1R,2R,3R,11S,12R,14R)-12-cyano-5-hydroxy-6-methoxy-7,21,30-trimethyl-26,27-dioxo-17,19,28-trioxa-24-thia-13,30-diazaheptacyclo[12.9.6.1~3,11~.0~2,13~.0~4,9~.0~15,23~.0~16,20~]triaconta-4,6,8,15,20,22-hexaen-22-yl acetate -Drug Synthesis Database

【结构式】

【分子编号】58648

【品名】(1R,2R,3R,11S,12R,14R)-12-cyano-5-hydroxy-6-methoxy-7,21,30-trimethyl-26,27-dioxo-17,19,28-trioxa-24-thia-13,30-diazaheptacyclo[12.9.6.1~3,11~.0~2,13~.0~4,9~.0~15,23~.0~16,20~]triaconta-4,6,8,15,20,22-hexaen-22-yl acetate

【CA登记号】

【分子式】C₃₁H₃₁N₃O₉S

【分子量】621.66796

【元素组成】C 59.89% H 5.03% N 6.76% O 23.16% S 5.16%

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：(LI)

Cleavage of the thioacetate bond of (XLIV) by means of hydrazine yields the thiol (XLV), which is cyclized by means of TFA in trifluoroethanol under high dilution conditions to afford the macrocyclic compound (XLVI). The reaction of (XLVI) with Ac2O and pyridine provides the acetate (XLVII), which is treated with Zn and HOAc in ethyl ether to eliminate the troc-protecting group, yielding (XLVIII). The reductive methylation of the NH group of (XLVIII) by means of HCHO, NaBH3CN and HOAc in methanol affords the N-methylamine derivative (XLIX), whose Alloc and ally ether groups are simultaneously eliminated by treatment with PdCl2(PPh3)2 and Bu3SnH in dichloromethane to provide the aminophenol (L). The transamination reaction of (L) with 4-formyl-1-methylpyridinium benzenesulfonate (FMPBS) and DBU in DMF/dichloromethane gives the alpha-ketolactone (LI).

参考文献中间体

合成目标

【1】 Abe, M.; Yanagisawa, A.; Tohma, S.; Kan, T.; Fukuyama, T.; Endo, A.; Total synthesis of ecteinascidin 743. J Am Chem Soc 2002, 124, 23, 6552.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XLIV)	58641	2,2,2-trichloroethyl (1R,2R,3S,13R,15R,16S)-13-{[((2R)-3-(acetylsulfanyl)-2-{[(allyloxy)carbonyl]amino}propanoyl)oxy]methyl}-22-(allyloxy)-15-cyano-3,5-dihydroxy-21-methoxy-6,20-dimethyl-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0~2,14~.0~4,12~.0~7,11~	C₄₀H₄₃Cl₃N₄O₁₃S	详情	详情
(XLV)	58642	2,2,2-trichloroethyl (1R,2R,3S,13R,15R,16S)-22-(allyloxy)-13-{[((2R)-2-{[(allyloxy)carbonyl]amino}-3-sulfanylpropanoyl)oxy]methyl}-15-cyano-3,5-dihydroxy-21-methoxy-6,20-dimethyl-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0~2,14~.0~4,12~.0~7,11~.0~18,23	C₃₈H₄₁Cl₃N₄O₁₂S	详情	详情
(XLVI)	58643	2,2,2-trichloroethyl (1R,2R,3R,11S,12R,14R,26R)-5-(allyloxy)-26-{[(allyloxy)carbonyl]amino}-12-cyano-22-hydroxy-6-methoxy-7,21-dimethyl-27-oxo-17,19,28-trioxa-24-thia-13,30-diazaheptacyclo[12.9.6.1~3,11~.0~2,13~.0~4,9~.0~15,23~.0~16,20~]triaconta-4,6,8,15,20,22-hexaen-22-yl acetate	C₃₈H₃₉Cl₃N₄O₁₁S	详情	详情
(XLVII)	58644	2,2,2-trichloroethyl (1R,2R,3R,11S,12R,14R,26R)-22-(acetyloxy)-5-(allyloxy)-26-{[(allyloxy)carbonyl]amino}-12-cyano-6-methoxy-7,21-dimethyl-27-oxo-17,19,28-trioxa-24-thia-13,30-diazaheptacyclo[12.9.6.1~3,11~.0~2,13~.0~4,9~.0~15,23~.0~16,20~]triaconta-4,6,8,15,20,22-hexaen-22-yl acetate	C₄₀H₄₁Cl₃N₄O₁₂S	详情	详情
(XLVIII)	58645	(1R,2R,3R,11S,12R,14R,26R)-5-(allyloxy)-26-{[(allyloxy)carbonyl]amino}-12-cyano-6-methoxy-7,21-dimethyl-27-oxo-17,19,28-trioxa-24-thia-13,30-diazaheptacyclo[12.9.6.1~3,11~.0~2,13~.0~4,9~.0~15,23~.0~16,20~]triaconta-4,6,8,15,20,22-hexaen-22-yl acetate	C₃₇H₄₀N₄O₁₀S	详情	详情
(XLIX)	58646	(1R,2R,3R,11S,12R,14R,26R)-5-(allyloxy)-26-{[(allyloxy)carbonyl]amino}-12-cyano-6-methoxy-7,21,30-trimethyl-27-oxo-17,19,28-trioxa-24-thia-13,30-diazaheptacyclo[12.9.6.1~3,11~.0~2,13~.0~4,9~.0~15,23~.0~16,20~]triaconta-4,6,8,15,20,22-hexaen-22-yl acetate	C₃₈H₄₂N₄O₁₀S	详情	详情
(L)	58647	(1R,2R,3R,11S,12R,14R,26R)-26-amino-12-cyano-5-hydroxy-6-methoxy-7,21,30-trimethyl-27-oxo-17,19,28-trioxa-24-thia-13,30-diazaheptacyclo[12.9.6.1~3,11~.0~2,13~.0~4,9~.0~15,23~.0~16,20~]triaconta-4,6,8,15,20,22-hexaen-22-yl acetate	C₃₁H₃₄N₄O₈S	详情	详情
(LI)	58648	(1R,2R,3R,11S,12R,14R)-12-cyano-5-hydroxy-6-methoxy-7,21,30-trimethyl-26,27-dioxo-17,19,28-trioxa-24-thia-13,30-diazaheptacyclo[12.9.6.1~3,11~.0~2,13~.0~4,9~.0~15,23~.0~16,20~]triaconta-4,6,8,15,20,22-hexaen-22-yl acetate	C₃₁H₃₁N₃O₉S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(LI)

The Pictet-Spengler cyclization of (LI) with 2-(3-hydroxy-4-methoxyphenyl)ethylamine (LII) by means of NaOAc in ethanol yields the spiro-tetrahydroisoquinoline (LIII). Finally, the nitrile group of (LIII) is treated with AgNO3 in acetonitrile/water to afford the target Ecteinascidin 743.

参考文献中间体

合成目标

【1】 Abe, M.; Yanagisawa, A.; Tohma, S.; Kan, T.; Fukuyama, T.; Endo, A.; Total synthesis of ecteinascidin 743. J Am Chem Soc 2002, 124, 23, 6552.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(LI)	58648	(1R,2R,3R,11S,12R,14R)-12-cyano-5-hydroxy-6-methoxy-7,21,30-trimethyl-26,27-dioxo-17,19,28-trioxa-24-thia-13,30-diazaheptacyclo[12.9.6.1~3,11~.0~2,13~.0~4,9~.0~15,23~.0~16,20~]triaconta-4,6,8,15,20,22-hexaen-22-yl acetate	C₃₁H₃₁N₃O₉S	详情	详情
(LII)	36471	5-(2-aminoethyl)-2-methoxyphenol	C₉H₁₃NO₂	详情	详情
(LIII)	58649		C₄₀H₄₂N₄O₁₀S	详情	详情

Extended Information