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【结 构 式】 
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【分子编号】58631 【品名】2,2,2-trichloroethyl (1R,9S,12R)-3-(benzyloxy)-12-({[tert-butyl(dimethyl)silyl]oxy}methyl)-11-[(1R)-2-hydroxy-1-(6-hydroxy-7-methyl-1,3-benzodioxol-4-yl)ethyl]-4-methoxy-5-methyl-10-oxo-11,13-diazatricyclo[7.3.1.0~2,7~]trideca-2,4,6-triene-13-carbox 【CA登记号】 |
【 分 子 式 】C40H49Cl3N2O10Si 【 分 子 量 】852.28014 【元素组成】C 56.37% H 5.79% Cl 12.48% N 3.29% O 18.77% Si 3.3% |
合成路线1
该中间体在本合成路线中的序号：(XXXIII)The hydrolysis of the mesylate group of (XXVI) with NaOH in refluxing MeOH/water, followed by reaction with Ac2O and pyridine gives the diacetate (XXVII). The cleavage of the Boc group of (XXVII) by means of TFA in dichloromethane, followed by reprotection with Troc-Cl and NaHCO3 in dichloromethane yields the expected compound (XXVIII). The reaction of (XXVIII) with dimethyldioxirane and CSA in MeOH/acetone affords the acid-sensitive epoxide (XXIX), which, without isolation, is treated with MeOH and CSA to provide the methoxy alcohol (XXX). The reduction of (XXX) with NaBH3CN and TFA provides the chiral alcohol (XXXI) as a single isomer, which is protected with Tbdms-Cl and imidazole to give the silyl ether (XXXII). Cleavage of the Ac groups of (XXXII) by means of guanidinium nitrate and NaOMe in methanol/dichloromethane yields the dihydroxy compound (XXXIII).
| 【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 |
|---|---|---|---|---|---|---|
| (XXVI) | 58624 | tert-butyl (1R,9S)-11-((1R)-2-(acetyloxy)-1-{7-methyl-6-[(methylsulfonyl)oxy]-1,3-benzodioxol-4-yl}ethyl)-3-(benzyloxy)-4-methoxy-5-methyl-12-methylene-10-oxo-11,13-diazatricyclo[7.3.1.0~2,7~]trideca-2,4,6-triene-13-carboxylate | C39H44N2O12S | 详情 | 详情 | |
| (XXVII) | 58625 | tert-butyl (1R,9S)-11-{(1R)-2-(acetyloxy)-1-[6-(acetyloxy)-7-methyl-1,3-benzodioxol-4-yl]ethyl}-3-(benzyloxy)-4-methoxy-5-methyl-12-methylene-10-oxo-11,13-diazatricyclo[7.3.1.0~2,7~]trideca-2,4,6-triene-13-carboxylate | C40H44N2O11 | 详情 | 详情 | |
| (XXVIII) | 58626 | 2,2,2-trichloroethyl (1R,9S)-11-{(1R)-2-(acetyloxy)-1-[6-(acetyloxy)-7-methyl-1,3-benzodioxol-4-yl]ethyl}-3-(benzyloxy)-4-methoxy-5-methyl-12-methylene-10-oxo-11,13-diazatricyclo[7.3.1.0~2,7~]trideca-2,4,6-triene-13-carboxylate | C38H37Cl3N2O11 | 详情 | 详情 | |
| (XXIX) | 58627 | C38H37Cl3N2O12 | 详情 | 详情 | ||
| (XXX) | 58628 | 2,2,2-trichloroethyl (1R,9S)-11-{(1R)-2-(acetyloxy)-1-[6-(acetyloxy)-7-methyl-1,3-benzodioxol-4-yl]ethyl}-3-(benzyloxy)-12-(hydroxymethyl)-4,12-dimethoxy-5-methyl-10-oxo-11,13-diazatricyclo[7.3.1.0~2,7~]trideca-2,4,6-triene-13-carboxylate | C39H41Cl3N2O13 | 详情 | 详情 | |
| (XXXI) | 58629 | 2,2,2-trichloroethyl (1R,9S,12R)-11-{(1R)-2-(acetyloxy)-1-[6-(acetyloxy)-7-methyl-1,3-benzodioxol-4-yl]ethyl}-3-(benzyloxy)-12-(hydroxymethyl)-4-methoxy-5-methyl-10-oxo-11,13-diazatricyclo[7.3.1.0~2,7~]trideca-2,4,6-triene-13-carboxylate | C38H39Cl3N2O12 | 详情 | 详情 | |
| (XXXII) | 58630 | 2,2,2-trichloroethyl (1R,9S,12R)-11-{(1R)-2-(acetyloxy)-1-[6-(acetyloxy)-7-methyl-1,3-benzodioxol-4-yl]ethyl}-3-(benzyloxy)-12-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-methoxy-5-methyl-10-oxo-11,13-diazatricyclo[7.3.1.0~2,7~]trideca-2,4,6-triene-1 | C44H53Cl3N2O12Si | 详情 | 详情 | |
| (XXXIII) | 58631 | 2,2,2-trichloroethyl (1R,9S,12R)-3-(benzyloxy)-12-({[tert-butyl(dimethyl)silyl]oxy}methyl)-11-[(1R)-2-hydroxy-1-(6-hydroxy-7-methyl-1,3-benzodioxol-4-yl)ethyl]-4-methoxy-5-methyl-10-oxo-11,13-diazatricyclo[7.3.1.0~2,7~]trideca-2,4,6-triene-13-carbox | C40H49Cl3N2O10Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXXIII)The selective protection of the phenolic OH of (XXXIII) by means of benzyl bromide and K2CO3 in refluxing acetonitrile gives the benzyl ether (XXXIV), which is reductocyclized by means of Red-Al in THF to yield the oxazolidine (XXXV). The cleavage of the oxazolidine ring of (XXXV) by means of Tms-CN and BF3/Et2O in dichloromethane affords the hydroxy nitrile (XXXVI), which is treated with Ac2O and pyridine to provide the acetate (XXXVII). The desilylation of (XXXVII) with HF in acetonitrile, followed by oxidation with DMP gives the carbaldehyde (XXXVIII), which is submitted to hydrogenolysis of the benzyl ethers by means of H2 over Pd/C in THF, performing a simultaneous cyclization to yield the pentacyclic compound (XXXIX). The reaction of (XXXIX) with allyl bromide (XL) and DIEA affords the allyl ether (XLI), which is treated with K2CO3 in methanol to provide the carbinol (XLII). The reaction of (XLII) with L-cysteine derivative (XLIII) by means of WSCD and DMAP in dichloromethane gives the corresponding ester (XLIV).
| 【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 |
|---|---|---|---|---|---|---|
| (XXIX) | 58637 | 2,2,2-trichloroethyl (1R,2R,3S,13R,15R,16S)-13-[(acetyloxy)methyl]-15-cyano-3,5,22-trihydroxy-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~]tetracosa-4,6,11,18,20,22-hexaene-24-carboxylate | C30H30Cl3N3O10 | 详情 | 详情 | |
| (XXXIII) | 58631 | 2,2,2-trichloroethyl (1R,9S,12R)-3-(benzyloxy)-12-({[tert-butyl(dimethyl)silyl]oxy}methyl)-11-[(1R)-2-hydroxy-1-(6-hydroxy-7-methyl-1,3-benzodioxol-4-yl)ethyl]-4-methoxy-5-methyl-10-oxo-11,13-diazatricyclo[7.3.1.0~2,7~]trideca-2,4,6-triene-13-carbox | C40H49Cl3N2O10Si | 详情 | 详情 | |
| (XXXIV) | 58632 | 2,2,2-trichloroethyl (1R,9S,12R)-3-(benzyloxy)-11-{(1R)-1-[6-(benzyloxy)-7-methyl-1,3-benzodioxol-4-yl]-2-hydroxyethyl}-12-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-methoxy-5-methyl-10-oxo-11,13-diazatricyclo[7.3.1.0~2,7~]trideca-2,4,6-triene-13-ca | C47H55Cl3N2O10Si | 详情 | 详情 | |
| (XXXV) | 58633 | 2,2,2-trichloroethyl (1R,9S,10S,13R,15R)-3-(benzyloxy)-13-[6-(benzyloxy)-7-methyl-1,3-benzodioxol-4-yl]-15-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-methoxy-5-methyl-11-oxa-14,16-diazatetracyclo[7.6.1.0~2,7~.0~10,14~]hexadeca-2,4,6-triene-16-carbox | C47H55Cl3N2O9Si | 详情 | 详情 | |
| (XXXVI) | 58634 | 2,2,2-trichloroethyl (1R,9S,10R,12R)-3-(benzyloxy)-11-{(1R)-1-[6-(benzyloxy)-7-methyl-1,3-benzodioxol-4-yl]-2-hydroxyethyl}-12-({[tert-butyl(dimethyl)silyl]oxy}methyl)-10-cyano-4-methoxy-5-methyl-11,13-diazatricyclo[7.3.1.0~2,7~]trideca-2,4,6-triene | C48H56Cl3N3O9Si | 详情 | 详情 | |
| (XXXVII) | 58635 | 2,2,2-trichloroethyl (1R,9S,10R,12R)-11-{(1R)-2-(acetyloxy)-1-[6-(benzyloxy)-7-methyl-1,3-benzodioxol-4-yl]ethyl}-3-(benzyloxy)-12-({[tert-butyl(dimethyl)silyl]oxy}methyl)-10-cyano-4-methoxy-5-methyl-11,13-diazatricyclo[7.3.1.0~2,7~]trideca-2,4,6-tr | C50H58Cl3N3O10Si | 详情 | 详情 | |
| (XXXVIII) | 58636 | 2,2,2-trichloroethyl (1R,9S,10R,12R)-11-{(1R)-2-(acetyloxy)-1-[6-(benzyloxy)-7-methyl-1,3-benzodioxol-4-yl]ethyl}-3-(benzyloxy)-10-cyano-12-formyl-4-methoxy-5-methyl-11,13-diazatricyclo[7.3.1.0~2,7~]trideca-2,4,6-triene-13-carboxylate | C44H42Cl3N3O10 | 详情 | 详情 | |
| (XL) | 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
| (XLI) | 58638 | 2,2,2-trichloroethyl (1R,2R,3S,13R,15R,16S)-13-[(acetyloxy)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~.0~18,23~]tetracosa-4,6,11,18,20,22-hexaene-24-carboxylate | C33H34Cl3N3O10 | 详情 | 详情 | |
| (XLII) | 58639 | 2,2,2-trichloroethyl (1R,2R,3S,13R,15R,16S)-22-(allyloxy)-15-cyano-3,5-dihydroxy-13-(hydroxymethyl)-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~]tetracosa-4,6,11,18,20,22-hexaene-24-carboxylate | C31H32Cl3N3O9 | 详情 | 详情 | |
| (XLIII) | 58640 | (2R)-3-(acetylsulfanyl)-2-{[(allyloxy)carbonyl]amino}propanoic acid | C9H13NO5S | 详情 | 详情 | |
| (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 |