【结 构 式】 |
【分子编号】58645 【品名】(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 【CA登记号】 |
【 分 子 式 】C37H40N4O10S 【 分 子 量 】732.81156 【元素组成】C 60.64% H 5.5% N 7.65% O 21.83% S 4.38% |
合成路线1
该中间体在本合成路线中的序号:(XLVIII)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).
【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 | CAS号 | 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 |