|
【结 构 式】 
|
【分子编号】42652 【品名】(1S,2R,3R,4S,6Z,8S,9S,10S,11Z,13S)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-14-((2S,3S,4S,5R)-4-[[tert-butyl(dimethyl)silyl]oxy]-3,5-dimethyl-6-oxotetrahydro-2H-pyran-2-yl)-13-hydroxy-2,4,6,8,10-pentamethyl-1-[(1S,2Z)-1-methyl-2,4-pentadienyl]-6,11-t 【CA登记号】 |
【 分 子 式 】C51H97NO8Si3 【 分 子 量 】936.58962 【元素组成】C 65.4% H 10.44% N 1.5% O 13.67% Si 9% |
合成路线1
该中间体在本合成路线中的序号：(XLIII)The condensation of aldehyde (XLI) with the intermediate ketoester (XXX) by means of chloro-(+)-disopinocampheylborane ((+)-IPCBCl) gives the 5-oxotetracosatetraenoic ester (XLII), which is submitted to reduction of the 5-oxo group with Me3N-BH(OAc)3, yielding a mixture of the 5-hydroxyester (XLIV) and the corresponding lactone (XLIII). Finally, this mixture, without separation of its components, is submitted to desilylation, with simultaneous lactonization, by treatment with HF and pyridine in THF.
| 【1】 Paterson, I.; et al.; Total synthesis of the antimicrotubule agent (+)-discodermolide using boron-mediated aldol reactions of chiral ketones. Angew Chem. Int Ed Engl 2000, 39, 2, 377. |
| 【2】 Paterson, I.; Florence, G.J.; Synthesis of (+)-discodermolide and analogues by control of asymmetric induction in aldol reactions of gamma-chiral (Z)-enals. Tetrahedron Lett 2000, 41, 35, 6935. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXX) | 42640 | methyl (2R,3S,4R)-3-[[tert-butyl(dimethyl)silyl]oxy]-2,4-dimethyl-5-oxohexanoate | C15H30O4Si | 详情 | 详情 | |
| (XLI) | 42650 | (1S,2R,3R,4S,6Z,8S,9S,10S,11Z)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-2,4,6,8,10-pentamethyl-1-[(1S,2Z)-1-methyl-2,4-pentadienyl]-13-oxo-6,11-tridecadienyl carbamate | C37H69NO5Si2 | 详情 | 详情 | |
| (XLII) | 42651 | methyl (2R,3S,4R,7S,8Z,10S,11S,12S,13Z,16S,17R,18R,19S,20S,21Z)-19-[(aminocarbonyl)oxy]-3,11,17-tris[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-2,4,10,12,14,16,18,20-octamethyl-5-oxo-8,13,21,23-tetracosatetraenoate | C52H99NO9Si3 | 详情 | 详情 | |
| (XLIII) | 42652 | (1S,2R,3R,4S,6Z,8S,9S,10S,11Z,13S)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-14-((2S,3S,4S,5R)-4-[[tert-butyl(dimethyl)silyl]oxy]-3,5-dimethyl-6-oxotetrahydro-2H-pyran-2-yl)-13-hydroxy-2,4,6,8,10-pentamethyl-1-[(1S,2Z)-1-methyl-2,4-pentadienyl]-6,11-t | C51H97NO8Si3 | 详情 | 详情 | |
| (XLIV) | 42653 | methyl (2R,3S,4S,5S,7S,8Z,10S,11S,12S,13Z,16S,17R,18R,19S,20S,21Z)-19-[(aminocarbonyl)oxy]-3,11,17-tris[[tert-butyl(dimethyl)silyl]oxy]-5,7-dihydroxy-2,4,10,12,14,16,18,20-octamethyl-8,13,21,23-tetracosatetraenoate | C52H101NO9Si3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XIX)Synthesis of the target (+)-Discodermolide: The selective oxidation of the chiral hexadecatrien-1,11-diol derivative (XII) with TEMPO and BAIB gives the hydroxyaldehyde (XIII), which is condensed with the phosphonate (XIV) by means of K2CO3 and 18-C-6 in toluene to yield the methyl ketone (XV). The reaction of the free OH group of (XV) with trichloroacetyl isocyanate and neutral alumina affords the carbamate (XVI), which is condensed with the chiral 5-oxopentanoic ester intermediate (XI) by means of (c-Hex)2B-Cl and TEA in ethyl ether to provide the chiral 5-hydroxy-7-oxotetracosatetraenoic ester (XVII). The cyclization of (XVII) by means of Ac-OH in aqueous THF furnishes the oxo- lactone (XVIII), which is reduced with K-Selectride in toluene/THF to give the hydroxy lactone (XIX). Finally, this compound is deprotected by means of HCl in methanol to provide the target (+)-Discodermolide.
| 【1】 Paterson, I.; Delgado, O.; Florence, G.J.; Lyothier, I.; Scott, J.P.; Sereinig, N.; 1,6-asymmetric induction in boron-mediated aldol reactions: Application to a practical total synthesis of (+)-discodermolide. Org Lett 2003, 5, 1, 35. |
| 【2】 Paterson, I.; Florence, G.J.; Gerlach, K.; Scott, J.P.; Sereinig, N.; A practical synthesis of (+)-discodermolide and analogues: Fragment union by complex aldol reactions. J Am Chem Soc 2001, 123, 39, 9535. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 62859 | methyl (2R,3S,4R)-3-{[tert-butyl(dimethyl)silyl]oxy}-2,4-dimethyl-5-oxopentanoate | C14H28O4Si | 详情 | 详情 | |
| (XII) | 42645 | (2S,3R,4S,5Z,8S,9R,10R,11S,12S,13Z)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-2,4,6,8,10,12-hexamethyl-5,13,15-hexadecatriene-1,11-diol | n/a | C34H68O4Si2 | 详情 | 详情 |
| (XIII) | 42646 | (2R,3R,4S,5Z,8S,9R,10R,11S,12S,13Z)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-11-hydroxy-2,4,6,8,10,12-hexamethyl-5,13,15-hexadecatrienal | n/a | C34H66O4Si2 | 详情 | 详情 |
| (XIV) | 62860 | bis(2,2,2-trifluoroethyl) 2-oxopropylphosphonate | C7H9F6O4P | 详情 | 详情 | |
| (XV) | 62861 | (3Z,5S,6S,7S,8Z,11S,12R,13R,14S,15S,16Z)-6,12-bis{[tert-butyl(dimethyl)silyl]oxy}-14-hydroxy-5,7,9,11,13,15-hexamethyl-3,8,16,18-nonadecatetraen-2-one | C37H70O4Si2 | 详情 | 详情 | |
| (XVI) | 62862 | (1S,2R,3R,4S,6Z,8S,9S,10S,11Z)-3,9-bis{[tert-butyl(dimethyl)silyl]oxy}-2,4,6,8,10-pentamethyl-1-[(1S,2Z)-1-methyl-2,4-pentadienyl]-13-oxo-6,11-tetradecadienyl carbamate | C38H71NO5Si2 | 详情 | 详情 | |
| (XVII) | 62863 | methyl (2R,3S,4S,5S,8Z,10S,11S,12S,13Z,16S,17R,18R,19S,20S,21Z)-19-[(aminocarbonyl)oxy]-3,11,17-tris{[tert-butyl(dimethyl)silyl]oxy}-5-hydroxy-2,4,10,12,14,16,18,20-octamethyl-7-oxo-8,13,21,23-tetracosatetraenoate | C52H99NO9Si3 | 详情 | 详情 | |
| (XVIII) | 62864 | (1S,2R,3R,4S,6Z,8S,9S,10S,11Z)-3,9-bis{[tert-butyl(dimethyl)silyl]oxy}-14-((2S,3S,4S,5R)-4-{[tert-butyl(dimethyl)silyl]oxy}-3,5-dimethyl-6-oxotetrahydro-2H-pyran-2-yl)-2,4,6,8,10-pentamethyl-1-[(1S,2Z)-1-methyl-2,4-pentadienyl]-13-oxo-6,11-tetradeca | C51H95NO8Si3 | 详情 | 详情 | |
| (XIX) | 42652 | (1S,2R,3R,4S,6Z,8S,9S,10S,11Z,13S)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-14-((2S,3S,4S,5R)-4-[[tert-butyl(dimethyl)silyl]oxy]-3,5-dimethyl-6-oxotetrahydro-2H-pyran-2-yl)-13-hydroxy-2,4,6,8,10-pentamethyl-1-[(1S,2Z)-1-methyl-2,4-pentadienyl]-6,11-t | C51H97NO8Si3 | 详情 | 详情 |