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【结 构 式】 
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【分子编号】46084 【品名】(2R)-1-(benzyloxy)-4-[(2R,3R)-3-(2-bromoethynyl)-3-methyloxiranyl]-2-butanol 【CA登记号】 |
【 分 子 式 】C16H19BrO3 【 分 子 量 】339.22906 【元素组成】C 56.65% H 5.65% Br 23.55% O 14.15% |
合成路线1
该中间体在本合成路线中的序号：(XXXI)Assembly of the target compound: The protection of the lactone (XXI) with benzyl trichloroacetimidate gives the benzyl ether (XXII), which is reduced with DIBAL in toluene to yield the lactol (XXIII). The reaction of (XXIII) with phosphorane (XXIV) in refluxing benzene affords the hydroxy-heptenoic ester (XXV), which is treated with Tbdms-Cl and imidazole to provide the silyl ether (XXVI). The reduction of the ester group of (XXVI) with DIBAL in dichloromethane furnishes the allylic alcohol (XXVII), which by a Sharpless asymmetric epoxidation gives the epoxyalcohol (XXVIII). The oxidation of the OH group of (XXVIII) with SO3/pyridine complex yields the epoxyaldehyde (XXIX), which by reaction with tetrabromomethane, PPh3 and TEA in dichloromethane affords the dibromovinyl derivative (XXX). The reaction of (XXX) with TBAF in THF provides the bromoacetylenic compound (XXXI), which is cyclized by means of BF3/Et2O complex in dichloromethane, furnishing the acetylenic tetrahydropyran (XXXII). The reaction of (XXXII) with Tes-Cl and imidazole in DMF gives the silyl ether (XXXIII), which is condensed with the intermediate carbaldehyde (IV) by means of CrCl2 in DMF to yield the propargyl alcohol (XXXIV). The oxidation of the OH group of (XXXIV) with MnO2 affords the corresponding ketone (XXXV), which is hydrogenated and deprotected with H2 over Pd/C in methanol to provide the saturated dihydroxyketone (XXXVI).
| 【1】 Forsyth, G.J.; Gonzalez, I.C.; Total synthesis of tryrsiferyl 23-acetate, a specific inhibitor of protein phosphatase 2A and anti-leukemic inducer of apoptosis. J Am Chem Soc 2000, 122, 38, 9099. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 40660 | CH5AlClN | 详情 | 详情 | ||
| (XXI) | 46090 | (5R)-5-(hydroxymethyl)dihydro-2(3H)-furanone | C5H8O3 | 详情 | 详情 | |
| (XXII) | 46076 | (5R)-5-[(benzyloxy)methyl]dihydro-2(3H)-furanone | C12H14O3 | 详情 | 详情 | |
| (XXIII) | 46077 | (5R)-5-[(benzyloxy)methyl]tetrahydro-2-furanol | C12H16O3 | 详情 | 详情 | |
| (XXIV) | 37071 | ethyl 2-(triphenylphosphoranylidene)propanoate | 5717-37-3 | C23H23O2P | 详情 | 详情 |
| (XXV) | 46078 | ethyl (E,6R)-7-(benzyloxy)-6-hydroxy-2-methyl-2-heptenoate | C17H24O4 | 详情 | 详情 | |
| (XXVI) | 46079 | ethyl (E,6R)-7-(benzyloxy)-6-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-2-heptenoate | C23H38O4Si | 详情 | 详情 | |
| (XXVII) | 46080 | (E,6R)-7-(benzyloxy)-6-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-2-hepten-1-ol | C21H36O3Si | 详情 | 详情 | |
| (XXVIII) | 46081 | [(2R,3R)-3-((3R)-4-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]butyl)-2-methyloxiranyl]methanol | C21H36O4Si | 详情 | 详情 | |
| (XXIX) | 46082 | (2S,3R)-3-((3R)-4-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]butyl)-2-methyl-2-oxiranecarbaldehyde | C21H34O4Si | 详情 | 详情 | |
| (XXX) | 46083 | benzyl (2R)-2-[[tert-butyl(dimethyl)silyl]oxy]-4-[(2R,3R)-3-(2,2-dibromovinyl)-3-methyloxiranyl]butyl ether; ([(1R)-1-[(benzyloxy)methyl]-3-[(2R,3R)-3-(2,2-dibromovinyl)-3-methyloxiranyl]propyl]oxy)(tert-butyl)dimethylsilane | C22H34Br2O3Si | 详情 | 详情 | |
| (XXXI) | 46084 | (2R)-1-(benzyloxy)-4-[(2R,3R)-3-(2-bromoethynyl)-3-methyloxiranyl]-2-butanol | C16H19BrO3 | 详情 | 详情 | |
| (XXXII) | 46085 | (2S,3R,6R)-6-[(benzyloxy)methyl]-2-(2-bromoethynyl)-2-methyltetrahydro-2H-pyran-3-ol | C16H19BrO3 | 详情 | 详情 | |
| (XXXIII) | 46086 | [[(2S,3R,6R)-6-[(benzyloxy)methyl]-2-(2-bromoethynyl)-2-methyltetrahydro-2H-pyran-3-yl]oxy](triethyl)silane; benzyl [(2R,5R,6S)-6-(2-bromoethynyl)-6-methyl-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-2-yl]methyl ether | C22H33BrO3Si | 详情 | 详情 | |
| (XXXIV) | 46087 | 3-[(2S,3R,6R)-6-[(benzyloxy)methyl]-2-methyl-3-[(triethylsilyl)oxy]tetrahydro-2H-pyran-2-yl]-1-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-2-propyn-1-ol | C31H49BrO5Si | 详情 | 详情 | |
| (XXXV) | 46088 | 3-[(2S,3R,6R)-6-[(benzyloxy)methyl]-2-methyl-3-[(triethylsilyl)oxy]tetrahydro-2H-pyran-2-yl]-1-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-2-propyn-1-one | C31H47BrO5Si | 详情 | 详情 | |
| (XXXVI) | 46089 | 1-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-3-[(2S,3R,6R)-3-hydroxy-6-(hydroxymethyl)-2-methyltetrahydro-2H-pyran-2-yl]-1-propanone | C18H31BrO5 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXXI)Assembly of the target compound: The protection of the lactone (XXI) with benzyl trichloroacetimidate gives the benzyl ether (XXII), which is reduced with DIBAL in toluene to yield the lactol (XXIII). The reaction of (XXIII) with phosphorane (XXIV) in refluxing benzene affords the hydroxy-heptenoic ester (XXV), which is treated with Tbdms-Cl and imidazole to provide the silyl ether (XXVI). The reduction of the ester group of (XXVI) with DIBAL in dichloromethane furnishes the allylic alcohol (XXVII), which by a Sharpless asymmetric epoxidation gives the epoxyalcohol (XXVIII). The oxidation of the OH group of (XXVIII) with SO3/pyridine complex yields the epoxyaldehyde (XXIX), which by reaction with tetrabromomethane, PPh3 and TEA in dichloromethane affords the dibromovinyl derivative (XXX). The reaction of (XXX) with TBAF in THF provides the bromoacetylenic compound (XXXI), which is cyclized by means of BF3/Et2O complex in dichloromethane, furnishing the acetylenic tetrahydropyran (XXXII). The reaction of (XXXII) with Tes-Cl and imidazole in DMF gives the silyl ether (XXXIII), which is condensed with the intermediate carbaldehyde (IV) by means of CrCl2 in DMF to yield the propargyl alcohol (XXXIV). The oxidation of the OH group of (XXXIV) with MnO2 affords the corresponding ketone (XXXV), which is hydrogenated and deprotected with H2 over Pd/C in methanol to provide the saturated dihydroxyketone (XXXVI).
| 【1】 Forsyth, G.J.; Gonzalez, I.C.; Total synthesis of tryrsiferyl 23-acetate, a specific inhibitor of protein phosphatase 2A and anti-leukemic inducer of apoptosis. J Am Chem Soc 2000, 122, 38, 9099. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 40660 | CH5AlClN | 详情 | 详情 | ||
| (XXI) | 46090 | (5R)-5-(hydroxymethyl)dihydro-2(3H)-furanone | C5H8O3 | 详情 | 详情 | |
| (XXII) | 46076 | (5R)-5-[(benzyloxy)methyl]dihydro-2(3H)-furanone | C12H14O3 | 详情 | 详情 | |
| (XXIII) | 46077 | (5R)-5-[(benzyloxy)methyl]tetrahydro-2-furanol | C12H16O3 | 详情 | 详情 | |
| (XXIV) | 37071 | ethyl 2-(triphenylphosphoranylidene)propanoate | 5717-37-3 | C23H23O2P | 详情 | 详情 |
| (XXV) | 46078 | ethyl (E,6R)-7-(benzyloxy)-6-hydroxy-2-methyl-2-heptenoate | C17H24O4 | 详情 | 详情 | |
| (XXVI) | 46079 | ethyl (E,6R)-7-(benzyloxy)-6-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-2-heptenoate | C23H38O4Si | 详情 | 详情 | |
| (XXVII) | 46080 | (E,6R)-7-(benzyloxy)-6-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-2-hepten-1-ol | C21H36O3Si | 详情 | 详情 | |
| (XXVIII) | 46081 | [(2R,3R)-3-((3R)-4-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]butyl)-2-methyloxiranyl]methanol | C21H36O4Si | 详情 | 详情 | |
| (XXIX) | 46082 | (2S,3R)-3-((3R)-4-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]butyl)-2-methyl-2-oxiranecarbaldehyde | C21H34O4Si | 详情 | 详情 | |
| (XXX) | 46083 | benzyl (2R)-2-[[tert-butyl(dimethyl)silyl]oxy]-4-[(2R,3R)-3-(2,2-dibromovinyl)-3-methyloxiranyl]butyl ether; ([(1R)-1-[(benzyloxy)methyl]-3-[(2R,3R)-3-(2,2-dibromovinyl)-3-methyloxiranyl]propyl]oxy)(tert-butyl)dimethylsilane | C22H34Br2O3Si | 详情 | 详情 | |
| (XXXI) | 46084 | (2R)-1-(benzyloxy)-4-[(2R,3R)-3-(2-bromoethynyl)-3-methyloxiranyl]-2-butanol | C16H19BrO3 | 详情 | 详情 | |
| (XXXII) | 46085 | (2S,3R,6R)-6-[(benzyloxy)methyl]-2-(2-bromoethynyl)-2-methyltetrahydro-2H-pyran-3-ol | C16H19BrO3 | 详情 | 详情 | |
| (XXXIII) | 46086 | [[(2S,3R,6R)-6-[(benzyloxy)methyl]-2-(2-bromoethynyl)-2-methyltetrahydro-2H-pyran-3-yl]oxy](triethyl)silane; benzyl [(2R,5R,6S)-6-(2-bromoethynyl)-6-methyl-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-2-yl]methyl ether | C22H33BrO3Si | 详情 | 详情 | |
| (XXXIV) | 46087 | 3-[(2S,3R,6R)-6-[(benzyloxy)methyl]-2-methyl-3-[(triethylsilyl)oxy]tetrahydro-2H-pyran-2-yl]-1-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-2-propyn-1-ol | C31H49BrO5Si | 详情 | 详情 | |
| (XXXV) | 46088 | 3-[(2S,3R,6R)-6-[(benzyloxy)methyl]-2-methyl-3-[(triethylsilyl)oxy]tetrahydro-2H-pyran-2-yl]-1-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-2-propyn-1-one | C31H47BrO5Si | 详情 | 详情 | |
| (XXXVI) | 46089 | 1-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-3-[(2S,3R,6R)-3-hydroxy-6-(hydroxymethyl)-2-methyltetrahydro-2H-pyran-2-yl]-1-propanone | C18H31BrO5 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XXXI)Assembly of the target compound: The protection of the lactone (XXI) with benzyl trichloroacetimidate gives the benzyl ether (XXII), which is reduced with DIBAL in toluene to yield the lactol (XXIII). The reaction of (XXIII) with phosphorane (XXIV) in refluxing benzene affords the hydroxy-heptenoic ester (XXV), which is treated with Tbdms-Cl and imidazole to provide the silyl ether (XXVI). The reduction of the ester group of (XXVI) with DIBAL in dichloromethane furnishes the allylic alcohol (XXVII), which by a Sharpless asymmetric epoxidation gives the epoxyalcohol (XXVIII). The oxidation of the OH group of (XXVIII) with SO3/pyridine complex yields the epoxyaldehyde (XXIX), which by reaction with tetrabromomethane, PPh3 and TEA in dichloromethane affords the dibromovinyl derivative (XXX). The reaction of (XXX) with TBAF in THF provides the bromoacetylenic compound (XXXI), which is cyclized by means of BF3/Et2O complex in dichloromethane, furnishing the acetylenic tetrahydropyran (XXXII). The reaction of (XXXII) with Tes-Cl and imidazole in DMF gives the silyl ether (XXXIII), which is condensed with the intermediate carbaldehyde (IV) by means of CrCl2 in DMF to yield the propargyl alcohol (XXXIV). The oxidation of the OH group of (XXXIV) with MnO2 affords the corresponding ketone (XXXV), which is hydrogenated and deprotected with H2 over Pd/C in methanol to provide the saturated dihydroxyketone (XXXVI).
| 【1】 Forsyth, G.J.; Gonzalez, I.C.; Total synthesis of tryrsiferyl 23-acetate, a specific inhibitor of protein phosphatase 2A and anti-leukemic inducer of apoptosis. J Am Chem Soc 2000, 122, 38, 9099. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 40660 | CH5AlClN | 详情 | 详情 | ||
| (XXI) | 46090 | (5R)-5-(hydroxymethyl)dihydro-2(3H)-furanone | C5H8O3 | 详情 | 详情 | |
| (XXII) | 46076 | (5R)-5-[(benzyloxy)methyl]dihydro-2(3H)-furanone | C12H14O3 | 详情 | 详情 | |
| (XXIII) | 46077 | (5R)-5-[(benzyloxy)methyl]tetrahydro-2-furanol | C12H16O3 | 详情 | 详情 | |
| (XXIV) | 37071 | ethyl 2-(triphenylphosphoranylidene)propanoate | 5717-37-3 | C23H23O2P | 详情 | 详情 |
| (XXV) | 46078 | ethyl (E,6R)-7-(benzyloxy)-6-hydroxy-2-methyl-2-heptenoate | C17H24O4 | 详情 | 详情 | |
| (XXVI) | 46079 | ethyl (E,6R)-7-(benzyloxy)-6-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-2-heptenoate | C23H38O4Si | 详情 | 详情 | |
| (XXVII) | 46080 | (E,6R)-7-(benzyloxy)-6-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-2-hepten-1-ol | C21H36O3Si | 详情 | 详情 | |
| (XXVIII) | 46081 | [(2R,3R)-3-((3R)-4-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]butyl)-2-methyloxiranyl]methanol | C21H36O4Si | 详情 | 详情 | |
| (XXIX) | 46082 | (2S,3R)-3-((3R)-4-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]butyl)-2-methyl-2-oxiranecarbaldehyde | C21H34O4Si | 详情 | 详情 | |
| (XXX) | 46083 | benzyl (2R)-2-[[tert-butyl(dimethyl)silyl]oxy]-4-[(2R,3R)-3-(2,2-dibromovinyl)-3-methyloxiranyl]butyl ether; ([(1R)-1-[(benzyloxy)methyl]-3-[(2R,3R)-3-(2,2-dibromovinyl)-3-methyloxiranyl]propyl]oxy)(tert-butyl)dimethylsilane | C22H34Br2O3Si | 详情 | 详情 | |
| (XXXI) | 46084 | (2R)-1-(benzyloxy)-4-[(2R,3R)-3-(2-bromoethynyl)-3-methyloxiranyl]-2-butanol | C16H19BrO3 | 详情 | 详情 | |
| (XXXII) | 46085 | (2S,3R,6R)-6-[(benzyloxy)methyl]-2-(2-bromoethynyl)-2-methyltetrahydro-2H-pyran-3-ol | C16H19BrO3 | 详情 | 详情 | |
| (XXXIII) | 46086 | [[(2S,3R,6R)-6-[(benzyloxy)methyl]-2-(2-bromoethynyl)-2-methyltetrahydro-2H-pyran-3-yl]oxy](triethyl)silane; benzyl [(2R,5R,6S)-6-(2-bromoethynyl)-6-methyl-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-2-yl]methyl ether | C22H33BrO3Si | 详情 | 详情 | |
| (XXXIV) | 46087 | 3-[(2S,3R,6R)-6-[(benzyloxy)methyl]-2-methyl-3-[(triethylsilyl)oxy]tetrahydro-2H-pyran-2-yl]-1-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-2-propyn-1-ol | C31H49BrO5Si | 详情 | 详情 | |
| (XXXV) | 46088 | 3-[(2S,3R,6R)-6-[(benzyloxy)methyl]-2-methyl-3-[(triethylsilyl)oxy]tetrahydro-2H-pyran-2-yl]-1-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-2-propyn-1-one | C31H47BrO5Si | 详情 | 详情 | |
| (XXXVI) | 46089 | 1-[(2S,5R)-5-bromo-2,6,6-trimethyltetrahydro-2H-pyran-2-yl]-3-[(2S,3R,6R)-3-hydroxy-6-(hydroxymethyl)-2-methyltetrahydro-2H-pyran-2-yl]-1-propanone | C18H31BrO5 | 详情 | 详情 |