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【结 构 式】 
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【分子编号】39457 【品名】(1S,3S,7R,11S,12S,15S,17R,21R,23R,25S)-1,11,21,25-tetrahydroxy-17-[(1R)-1-hydroxyethyl]-5,13-bis[(E)-2-methoxy-2-oxoethylidene]-10,10,26,26-tetramethyl-19-oxo-18,27,28,29-tetraoxatetracyclo[21.3.1.1(3,7).1(11,15)]nonacos-8-en-12-yl (2E,4E)-2,4-octadienoate 【CA登记号】 |
【 分 子 式 】C45H66O16 【 分 子 量 】863.00944 【元素组成】C 62.63% H 7.71% O 29.66% |
合成路线1
该中间体在本合成路线中的序号：(LXVII)The desilylation and C9 demethylation of (LXI) with PPTS in THF/H2O gives the dihydroxy intermediate (LXII), which is deacetylated with Na2CO3 in MeOH to yield the trihydroxy intermediate (LXIII). The demethylation of the C19 methoxy group of (LXIII) with TsOH in CH3CN/H2O affords the tetrahydroxy compound (LXIV), which is selectively acylated at the C20 hydroxy group with 2(E),4(E)-octadienoic acid (LXV) by means of diisopropylcarbodiimidde (DIP) and DMAP in CH2Cl2 providing the ester (LXVI). The elimination of the 4-methoxybenzyl protecting groups of (LXVII) by means of DDQ in a buffered solution gives the precursor Bryostatin 2 (LXVII).
| 【1】 Lautens, M.; Prunet, J.A.; Carreira, E.M.; Carter, P.H.; Charette, A.B.; Evans, D.A.; Total synthesis of bryostatin 2. J Am Chem Soc 1999, 121, 33, 7540. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (LXI) | 39451 | methyl 2-[(1S,3S,7R,11S,12S,15S,17R,21R,23S,25S)-1,11-dimethoxy-12-[(2-methoxyacetyl)oxy]-25-[(4-methoxybenzyl)oxy]-17-[(1R)-1-[(4-methoxybenzyl)oxy]ethyl]-13-[(E)-2-methoxy-2-oxoethylidene]-10,10,26,26-tetramethyl-19-oxo-21-[(triethylsilyl)oxy]-18,27,28,29-tetraoxatetracyclo[21.3.1.1(3,7).1(11,15)]nonacos-8-en-5-ylidene]acetate | C64H94O19Si | 详情 | 详情 | |
| (LXII) | 39452 | methyl 2-[(1S,3S,7R,11S,12S,15S,17R,21R,23R,25S)-1,21-dihydroxy-11-methoxy-12-[(2-methoxyacetyl)oxy]-25-[(4-methoxybenzyl)oxy]-17-[(1R)-1-[(4-methoxybenzyl)oxy]ethyl]-13-[(E)-2-methoxy-2-oxoethylidene]-10,10,26,26-tetramethyl-19-oxo-18,27,28,29-tetraoxatetracyclo[21.3.1.1(3,7).1(11,15)]nonacos-8-en-5-ylidene]acetate | C57H78O19 | 详情 | 详情 | |
| (LXIII) | 39453 | methyl 2-[(1S,3S,7R,11S,12S,15S,17R,21R,23R,25S)-1,12,21-trihydroxy-11-methoxy-25-[(4-methoxybenzyl)oxy]-17-[(1R)-1-[(4-methoxybenzyl)oxy]ethyl]-13-[(E)-2-methoxy-2-oxoethylidene]-10,10,26,26-tetramethyl-19-oxo-18,27,28,29-tetraoxatetracyclo[21.3.1.1(3,7).1(11,15)]nonacos-8-en-5-ylidene]acetate | C54H74O17 | 详情 | 详情 | |
| (LXIV) | 39454 | methyl 2-[(1S,3S,7R,11S,12S,15S,17R,21R,23R,25S)-1,11,12,21-tetrahydroxy-25-[(4-methoxybenzyl)oxy]-17-[(1R)-1-[(4-methoxybenzyl)oxy]ethyl]-13-[(E)-2-methoxy-2-oxoethylidene]-10,10,26,26-tetramethyl-19-oxo-18,27,28,29-tetraoxatetracyclo[21.3.1.1(3,7).1(11,15)]nonacos-8-en-5-ylidene]acetate | C53H72O17 | 详情 | 详情 | |
| (LXV) | 39455 | (2E,4E)-2,4-octadienoic acid | C8H12O2 | 详情 | 详情 | |
| (LXVI) | 39456 | (1S,3S,7R,11S,12S,15S,17R,21R,23R,25S)-1,11,21-trihydroxy-25-[(4-methoxybenzyl)oxy]-17-[(1R)-1-[(4-methoxybenzyl)oxy]ethyl]-5,13-bis[(E)-2-methoxy-2-oxoethylidene]-10,10,26,26-tetramethyl-19-oxo-18,27,28,29-tetraoxatetracyclo[21.3.1.1(3,7).1(11,15)]nonacos-8-en-12-yl (2E,4E)-2,4-octadienoate | C61H82O18 | 详情 | 详情 | |
| (LXVII) | 39457 | (1S,3S,7R,11S,12S,15S,17R,21R,23R,25S)-1,11,21,25-tetrahydroxy-17-[(1R)-1-hydroxyethyl]-5,13-bis[(E)-2-methoxy-2-oxoethylidene]-10,10,26,26-tetramethyl-19-oxo-18,27,28,29-tetraoxatetracyclo[21.3.1.1(3,7).1(11,15)]nonacos-8-en-12-yl (2E,4E)-2,4-octadienoate | C45H66O16 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(LXVII)The selective silylation of (LXVII) with TBMDSCl, Et3N and DMAP in DMF gives the 26-TBDMS ether (LXVIII), which is acetylated with Ac2O and pyridine yielding the 7-acetate (LXIX). Finally, (LXIX) is desilylated with HF in acetonitrile.
| 【1】 Pettit, G.R.; et al.; Synthetic conversion of bryostatin 2 to bryostatin 1 and related bryopyrans. Can J Chem 1991, 69, 856. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (LXVII) | 39457 | (1S,3S,7R,11S,12S,15S,17R,21R,23R,25S)-1,11,21,25-tetrahydroxy-17-[(1R)-1-hydroxyethyl]-5,13-bis[(E)-2-methoxy-2-oxoethylidene]-10,10,26,26-tetramethyl-19-oxo-18,27,28,29-tetraoxatetracyclo[21.3.1.1(3,7).1(11,15)]nonacos-8-en-12-yl (2E,4E)-2,4-octadienoate | C45H66O16 | 详情 | 详情 | |
| (LXVIII) | 39458 | (1S,3S,7R,11S,12S,15S,17R,21R,23R,25S)-17-((1R)-1-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-1,11,21,25-tetrahydroxy-5,13-bis[(E)-2-methoxy-2-oxoethylidene]-10,10,26,26-tetramethyl-19-oxo-18,27,28,29-tetraoxatetracyclo[21.3.1.1(3,7).1(11,15)]nonacos-8-en-12-yl (2E,4E)-2,4-octadienoate | C51H80O16Si | 详情 | 详情 | |
| (LXIX) | 39459 | (1S,3S,7R,11S,12S,15S,17R,21R,23R,25S)-25-(acetoxy)-17-((1R)-1-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-1,11,21-trihydroxy-5,13-bis[(E)-2-methoxy-2-oxoethylidene]-10,10,26,26-tetramethyl-19-oxo-18,27,28,29-tetraoxatetracyclo[21.3.1.1(3,7).1(11,15)]nonacos-8-en-12-yl (2E,4E)-2,4-octadienoate | C53H82O17Si | 详情 | 详情 |