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【结 构 式】 
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【分子编号】62539 【品名】tert-butyl (3S,6R,7S,10R,11S,15S,17S,20S,25aS)-11-hydroxy-20-isobutyl-15-isopropyl-3-(4-methoxybenzyl)-2,6,17-trimethyl-10-[(1S)-1-methylpropyl]-1,4,8,13,16,18,21-heptaoxodocosahydro-15H-pyrrolo[2,1-f][1,15,4,7,10,20]dioxatetraazacyclotricosin-7-ylc 【CA登记号】 |
【 分 子 式 】C47H73N5O13 【 分 子 量 】916.12252 【元素组成】C 61.62% H 8.03% N 7.64% O 22.7% |
合成路线1
该中间体在本合成路线中的序号：(XXIV)Coupling between segments (VI) and (XXI) by means of HBTU gave rise to the depsipeptide (XXII). Simultaneous deprotection of the C- and N-terminal functions of (XXII) by hydrogenolysis led to the linear precursor (XXIII), which was then cyclized to (XXIV) in the presence of HATU and HOAt
| 【1】 Jou, G.; Gonzalez, I.; Albericio, F.; Lloyd-Williams, P.; Giralt, E.; Total synthesis of dehydrodidemnin B. Use of uronium and phosphonium salt coupling reagents in peptide synthesis in solution. J Org Chem 1997, 62, 2, 354. |
| 【2】 Giralt Lledo, E.; Albericio Palomera, F.; Lloyd-Williams, P.; Gonzalez Valcarcel, I.; Jou Prat, G.; Gomez Gonzalez, A.; Manzanares Secades, I. (PharmaMar, SA); Process for the preparation of didemnine A. ES 2102322 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 52709 | (2S,3R)-3-{[(2S)-2-[[(benzyloxy)carbonyl](methyl)amino]-3-(4-methoxyphenyl)propanoyl]oxy}-2-[(tert-butoxycarbonyl)amino]butanoic acid | C28H36N2O9 | 详情 | 详情 | |
| (XXI) | 62536 | benzyl (2S)-1-{(2S)-2-[((4S)-4-{[(3S,4R,5S)-4-amino-3-hydroxy-5-methylheptanoyl]oxy}-2,5-dimethyl-3-oxohexanoyl)amino]-4-methylpentanoyl}-2-pyrrolidinecarboxylate | C34H53N3O8 | 详情 | 详情 | |
| (XXII) | 62537 | benzyl (2S)-1-{(2S,7S,11S,12R,15S,16R,19S)-15-[(tert-butoxycarbonyl)amino]-11-hydroxy-2-isobutyl-7-isopropyl-19-(4-methoxybenzyl)-5,16,20-trimethyl-12-[(1S)-1-methylpropyl]-4,6,9,14,18,21-hexaoxo-23-phenyl-8,17,22-trioxa-3,13,20-triazatricos-1-anoyl | C62H87N5O16 | 详情 | 详情 | |
| (XXIII) | 62538 | (2S)-1-{(2S,7S,11S,12R,15S,16R,19S)-15-[(tert-butoxycarbonyl)amino]-11-hydroxy-2-isobutyl-7-isopropyl-19-(4-methoxybenzyl)-5,16-dimethyl-12-[(1S)-1-methylpropyl]-4,6,9,14,18-pentaoxo-8,17-dioxa-3,13,20-triazahenicos-1-anoyl}-2-pyrrolidinecarboxylic | C47H75N5O14 | 详情 | 详情 | |
| (XXIV) | 62539 | tert-butyl (3S,6R,7S,10R,11S,15S,17S,20S,25aS)-11-hydroxy-20-isobutyl-15-isopropyl-3-(4-methoxybenzyl)-2,6,17-trimethyl-10-[(1S)-1-methylpropyl]-1,4,8,13,16,18,21-heptaoxodocosahydro-15H-pyrrolo[2,1-f][1,15,4,7,10,20]dioxatetraazacyclotricosin-7-ylc | C47H73N5O13 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXIV)Removal of the N-Boc protecting group of (XXIV) by means of HCl in dioxane generated the macrocyclic amine (XXV). The protected aminoacid (XXVII) was prepared by treatment of D-leucine (XXVI) with Boc2O, followed by N-methylation under phase-transfer conditions. Coupling of N-Boc-N-methyl-D-leucine (XXVII) with amine (XXV) provided amide (XXVIII). Then, acidic Boc group cleavage in (XXVIII) furnished didemnin A (XXIX)
| 【1】 Jou, G.; Gonzalez, I.; Albericio, F.; Lloyd-Williams, P.; Giralt, E.; Total synthesis of dehydrodidemnin B. Use of uronium and phosphonium salt coupling reagents in peptide synthesis in solution. J Org Chem 1997, 62, 2, 354. |
| 【2】 Giralt Lledo, E.; Albericio Palomera, F.; Lloyd-Williams, P.; Gonzalez Valcarcel, I.; Jou Prat, G.; Gomez Gonzalez, A.; Manzanares Secades, I. (PharmaMar, SA); Process for the preparation of didemnine A. ES 2102322 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXIV) | 62539 | tert-butyl (3S,6R,7S,10R,11S,15S,17S,20S,25aS)-11-hydroxy-20-isobutyl-15-isopropyl-3-(4-methoxybenzyl)-2,6,17-trimethyl-10-[(1S)-1-methylpropyl]-1,4,8,13,16,18,21-heptaoxodocosahydro-15H-pyrrolo[2,1-f][1,15,4,7,10,20]dioxatetraazacyclotricosin-7-ylc | C47H73N5O13 | 详情 | 详情 | |
| (XXV) | 50768 | (3S,6R,7S,10R,11S,15S,17S,20S,25aS)-7-amino-11-hydroxy-20-isobutyl-15-isopropyl-3-(4-methoxybenzyl)-2,6,17-trimethyl-10-[(1S)-1-methylpropyl]tetradecahydro-15H-pyrrolo[2,1-f][1,15,4,7,10,20]dioxatetraazacyclotricosine-1,4,8,13,16,18,21(17H)-heptone | C42H65N5O11 | 详情 | 详情 | |
| (XXVI) | 16010 | D-leucine | 328-38-1 | C6H13NO2 | 详情 | 详情 |
| (XXVII) | 50788 | (2R)-2-[(tert-butoxycarbonyl)(methyl)amino]-4-methylpentanoic acid | C12H23NO4 | 详情 | 详情 | |
| (XXVIII) | 62540 | tert-butyl (1R)-1-[({(3S,6R,7S,10R,11S,15S,17S,20S,25aS)-11-hydroxy-20-isobutyl-15-isopropyl-3-(4-methoxybenzyl)-2,6,17-trimethyl-10-[(1S)-1-methylpropyl]-1,4,8,13,16,18,21-heptaoxodocosahydro-15H-pyrrolo[2,1-f][1,15,4,7,10,20]dioxatetraazacyclotric | C54H86N6O14 | 详情 | 详情 | |
| (XXIX) | 50796 | (2R)-N-[(3S,6R,7S,10R,11S,15S,17S,20S,25aS)-11-hydroxy-20-isobutyl-15-isopropyl-3-(4-methoxybenzyl)-2,6,17-trimethyl-10-[(1S)-1-methylpropyl]-1,4,8,13,16,18,21-heptaoxodocosahydro-15H-pyrrolo[2,1-f][1,15,4,7,10,20]dioxatetraazacyclotricosin-7-yl]-4-methyl-2-(methylamino)pentanamide | C49H78N6O12 | 详情 | 详情 |