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【结 构 式】 
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【分子编号】36466 【品名】(1R,2S,4R,13R,15R,16S)-4-hydroxy-13-(hydroxymethyl)-21-methoxy-22-(methoxymethoxy)-6,20,24-trimethyl-5-oxo-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0(2,14).0(4,12).0(7,11).0(18,23)]tetracosa-6,11,18,20,22-pentaene-15-carbonitrile 【CA登记号】 |
【 分 子 式 】C28H33N3O8 【 分 子 量 】539.58544 【元素组成】C 62.33% H 6.16% N 7.79% O 23.72% |
合成路线1
该中间体在本合成路线中的序号：(XVIII)The selective trifluoromethanesulfonation of the least hindered phenolic OH group of (XI) with Tf2NPh, TEA and DMAP gives monosulfonate (XII), which is selectively silylated at the primary OH group with TBDPSCl yielding silyl ether (XIII). The protection of the last OH group of (XIII) with Mom-Br and DIEA affords the fully protected intermediate (XIV), which is deallylated with Bu3SnH and PdCl2(PPh3)2 to give the intermediate (XV). The reductive methylation of the NH group of (XV) with formaldehyde and NaBH3CN yields the N-methyl derivative (XVI). The replacement of the CF3SO3 group of (XVI) by methyl is performed by treatment with Me4Sn and PdCl2(PPh3)2 in hot DMF provides the phenol (XVII), which is oxidized with (PhSeO)2O and desilylated with TBAF to give the dihydroxydienone (XVIII).
| 【1】 Gin, D.Y.; Corey, E.J.; Kania, R.S.; Enantioselective total synthesis of Ecteinascidin 743. J Am Chem Soc 1996, 118, 38, 9202-03. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 36459 | allyl (1R,2S,13R,15R,16S)-5-(allyloxy)-15-cyano-20,22-dihydroxy-13-(hydroxymethyl)-21-methoxy-6-methyl-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0(2,14).0(4,12).0(7,11).0(18,23)]tetracosa-4,6,11,18,20,22-hexaene-24-carboxylate | C31H33N3O9 | 详情 | 详情 | |
| (XII) | 36460 | allyl (1R,2S,13R,15R,16S)-5-(allyloxy)-15-cyano-22-hydroxy-13-(hydroxymethyl)-21-methoxy-6-methyl-20-[[(trifluoromethyl)sulfonyl]oxy]-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0(2,14).0(4,12).0(7,11).0(18,23)]tetracosa-4,6,11,18,20,22-hexaene-24-carbox | C32H32F3N3O11S | 详情 | 详情 | |
| (XIII) | 36461 | allyl (1R,2S,13R,15R,16S)-5-(allyloxy)-13-([[tert-butyl(diphenyl)silyl]oxy]methyl)-15-cyano-22-hydroxy-21-methoxy-6-methyl-20-[[(trifluoromethyl)sulfonyl]oxy]-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0(2,14).0(4,12).0(7,11).0(18,23)]tetracosa-4,6,11,1 | C48H50F3N3O11SSi | 详情 | 详情 | |
| (XIV) | 36462 | allyl (1R,2S,13R,15R,16S)-5-(allyloxy)-13-([[tert-butyl(diphenyl)silyl]oxy]methyl)-15-cyano-21-methoxy-22-(methoxymethoxy)-6-methyl-20-[[(trifluoromethyl)sulfonyl]oxy]-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0(2,14).0(4,12).0(7,11).0(18,23)]tetracosa | C50H54F3N3O12SSi | 详情 | 详情 | |
| (XV) | 36463 | (1R,2S,13R,15R,16S)-13-([[tert-butyl(diphenyl)silyl]oxy]methyl)-15-cyano-5-hydroxy-21-methoxy-22-(methoxymethoxy)-6-methyl-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0(2,14).0(4,12).0(7,11).0(18,23)]tetracosa-4,6,11,18,20,22-hexaen-20-yl trifluoromethan | C43H46F3N3O10SSi | 详情 | 详情 | |
| (XVI) | 36464 | (1R,2S,13R,15R,16S)-13-([[tert-butyl(diphenyl)silyl]oxy]methyl)-15-cyano-5-hydroxy-21-methoxy-22-(methoxymethoxy)-6,24-dimethyl-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0(2,14).0(4,12).0(7,11).0(18,23)]tetracosa-4,6,11,18,20,22-hexaen-20-yl trifluorom | C44H48F3N3O10SSi | 详情 | 详情 | |
| (XVII) | 36465 | (1R,2S,13R,15R,16S)-13-([[tert-butyl(diphenyl)silyl]oxy]methyl)-5-hydroxy-21-methoxy-22-(methoxymethoxy)-6,20,24-trimethyl-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0(2,14).0(4,12).0(7,11).0(18,23)]tetracosa-4,6,11,18,20,22-hexaene-15-carbonitrile | C44H51N3O7Si | 详情 | 详情 | |
| (XVIII) | 36466 | (1R,2S,4R,13R,15R,16S)-4-hydroxy-13-(hydroxymethyl)-21-methoxy-22-(methoxymethoxy)-6,20,24-trimethyl-5-oxo-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0(2,14).0(4,12).0(7,11).0(18,23)]tetracosa-6,11,18,20,22-pentaene-15-carbonitrile | C28H33N3O8 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XVIII)The esterification of the primary OH group of (XVIII) with the protected cysteine (XIX) by means of EDC and DMAP in dichloromethane gives ester (XX), which is cyclized by means of trifluoromethanesulfonic anhydride and DMSO yielding the bridged lactone (XXI). The oxidation of (XXI) with N-methylpyridinium-4-carbaldehyde (NMPA), DBU and PdCl2(PPh3)2 affords the oxolactone (XXII), which is finally cyclized with 2-(3-hydroxy-4-methoxyphenyl)ethylamine (XXIII) by means of TFA and AgNO3 in water.
| 【1】 Gin, D.Y.; Corey, E.J.; Kania, R.S.; Enantioselective total synthesis of Ecteinascidin 743. J Am Chem Soc 1996, 118, 38, 9202-03. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVIII) | 36466 | (1R,2S,4R,13R,15R,16S)-4-hydroxy-13-(hydroxymethyl)-21-methoxy-22-(methoxymethoxy)-6,20,24-trimethyl-5-oxo-8,10-dioxa-14,24-diazahexacyclo[14.7.1.0(2,14).0(4,12).0(7,11).0(18,23)]tetracosa-6,11,18,20,22-pentaene-15-carbonitrile | C28H33N3O8 | 详情 | 详情 | |
| (XIX) | 36467 | (2R)-2-[[(allyloxy)carbonyl]amino]-3-[(9H-fluoren-9-ylmethyl)sulfanyl]propionic acid | C21H21NO4S | 详情 | 详情 | |
| (XX) | 36468 | C49H52N4O11S | 详情 | 详情 | ||
| (XXI) | 36469 | (1R,2R,3R,11S,12R,14R)-26-[[(allyloxy)carbonyl]amino]-12-cyano-6-methoxy-5-(methoxymethoxy)-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 | C37H42N4O11S | 详情 | 详情 | |
| (XXII) | 36470 | (1R,2R,3R,11S,12R,14R)-12-cyano-6-methoxy-5-(methoxymethoxy)-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 | C33H35N3O10S | 详情 | 详情 | |
| (XXIII) | 36471 | 5-(2-aminoethyl)-2-methoxyphenol | C9H13NO2 | 详情 | 详情 |