|
【结 构 式】 
|
【分子编号】39451 【品名】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 【CA登记号】 |
【 分 子 式 】C64H94O19Si 【 分 子 量 】1195.52446 【元素组成】C 64.3% H 7.93% O 25.43% Si 2.35% |
合成路线1
该中间体在本合成路线中的序号：(LXI)The reaction of (LIII) with HF in pyridine/methanol gives the desilylated tricyclic intermediate (LIV), which is resilylated with TESCl and DMAP in dichloromethane and debenzylated by reaction with 1,4-cyclohexadiene over Pd/C to afford the free hydroxyacid (LV). The cyclization of (LV) by means of 2,4,6-trichlorobenzoyl chloride, i-PrNEt2 and DMAP gives the macrocycle (LVI), which is selectively deprotected with PPTS in methanol/HC(OEt)3/dichloromethane, and oxidized with Dess Martin periodinane (DMP) in pyridine/dichloromethane yielding the diketone (LVII). The reaction of (LVII) with the Fuji's chiral phosphonate (LVIII) by means of NaHMDS in THF affords the C13 enoate (LIX), which is condensed with methyl glyoxylate by means of KHMDS in THF to give the C21 enoate (LX). The stereoselective reduction of the carbonyl group of (LX) with BH3/SMe2 catalyzed by the oxazaborolidine (A), followed by esterification with methoxyacetic anhydride provides the methoxyacetate (LXI).
| 【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 |
|---|---|---|---|---|---|---|
| 40732 | methyl 2-oxoacetate | 922-68-9 | C3H4O3 | 详情 | 详情 | |
| (A) | 39460 | 1-methyl-3,3-diphenyltetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborole | C18H20BNO | 详情 | 详情 | |
| (LIII) | 39443 | C79H132O15Si4 | 详情 | 详情 | ||
| (LIV) | 39444 | C56H78O15 | 详情 | 详情 | ||
| (LV) | 39445 | C61H100O15Si2 | 详情 | 详情 | ||
| (LVI) | 39446 | C61H98O14Si2 | 详情 | 详情 | ||
| (LVII) | 39447 | (1S,3S,7R,11S,15S,17R,21R,23S,25S)-1,11-dimethoxy-25-[(4-methoxybenzyl)oxy]-17-[(1R)-1-[(4-methoxybenzyl)oxy]ethyl]-10,10,26,26-tetramethyl-21-[(triethylsilyl)oxy]-18,27,28,29-tetraoxatetracyclo[21.3.1.1(3,7).1(11,15)]nonacos-8-ene-5,12,19-trione | C55H82O14Si | 详情 | 详情 | |
| (LVIII) | 39448 | methyl 2-(2-oxo-2lambda(5)-dinaphtho[2,1-d:1,2-f][1,3,2]dioxaphosphepin-2-yl)acetate | C23H17O5P | 详情 | 详情 | |
| (LIX) | 39449 | methyl 2-[(1S,3S,7R,11S,15S,17R,21R,23S,25S)-1,11-dimethoxy-25-[(4-methoxybenzyl)oxy]-17-[(1R)-1-[(4-methoxybenzyl)oxy]ethyl]-10,10,26,26-tetramethyl-12,19-dioxo-21-[(triethylsilyl)oxy]-18,27,28,29-tetraoxatetracyclo[21.3.1.1(3,7).1(11,15)]nonacos-8-en-5-ylidene]acetate | C58H86O15Si | 详情 | 详情 | |
| (LX) | 39450 | methyl 2-[(1S,3S,7R,11S,15S,17R,21R,23S,25S)-1,11-dimethoxy-25-[(4-methoxybenzyl)oxy]-17-[(1R)-1-[(4-methoxybenzyl)oxy]ethyl]-13-[(E)-2-methoxy-2-oxoethylidene]-10,10,26,26-tetramethyl-12,19-dioxo-21-[(triethylsilyl)oxy]-18,27,28,29-tetraoxatetracyclo[21.3.1.1(3,7).1(11,15)]nonacos-8-en-5-ylidene]acetate | C61H88O17Si | 详情 | 详情 | |
| (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 |
合成路线2
该中间体在本合成路线中的序号：(LXI)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 |