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【结 构 式】 
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【分子编号】49655 【品名】(2R,4R,5Z,7Z,9E)-4-[[tert-butyl(dimethyl)silyl]oxy]-11-[[tert-butyl(diphenyl)silyl]oxy]-2-[(triethylsilyl)oxy]-5,7,9-undecatrien-1-ol 【CA登记号】 |
【 分 子 式 】C39H64O4Si3 【 分 子 量 】681.19126 【元素组成】C 68.77% H 9.47% O 9.39% Si 12.37% |
合成路线1
该中间体在本合成路线中的序号：(XXII)Synthesis of fostriecin: The reduction of tetrahydrofuranone (VI) with DIBAL gives the lactol (VII), which is mesylated with Ms-Cl and treated with TEA to yield the dihydrofuran (VIII). The Sharpless asymmetric dihydroxylation of (VIII) with (DHQD)2AQN affords the diol (IX), which is selectively monosilylated with Tbdms-OTf, providing the silyl ether (X). The condensation of the lactol (X) with phosphonate (XI) by means of KHMDS gives the methyl heptenoate (XII). The silylation of the OH group of (XII) with Tes-OTf yields the disilylated ester (XIII), which is reduced with DIBAL to afford the primary alcohol (XIV). The oxidation of (XIV) with DMP provides the corresponding aldehyde (XV), which is treated with CBr4 and PPH3 to furnish the alpha,alpha-dibromodiene (XVI). Elimination of the Pmb-protecting group of (XVI) with DDQ gives the primary alcohol (XVII), which is treated with Ac2O to yield the acetate (XVIII). The selective monodebromination of (XVIII) with Bu3SnH and Pd(PPh3)4 affords the bromoolefin (XIX), which is condensed with tributylstannane (XX) to provide the adduct (XXI). Cleavage of the acetoxy group of (XXI) by means of DIBAL gives the primary alcohol (XXII).
| 【1】 Boger, D.L.; et al.; Total synthesis of fostriecin (CI-920). J Am Chem Soc 2001, 123, 18, 4161. |
| 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) | 49640 | (5R)-5-[[(4-methoxybenzyl)oxy]methyl]dihydro-2(3H)-furanone | C13H16O4 | 详情 | 详情 | |
| (VII) | 49641 | (5R)-5-[[(4-methoxybenzyl)oxy]methyl]tetrahydro-2-furanol | C13H18O4 | 详情 | 详情 | |
| (VIII) | 49642 | (2R)-2-[[(4-methoxybenzyl)oxy]methyl]-2,3-dihydrofuran; 4-[[(2R)-2,3-dihydro-2-furanylmethoxy]methyl]phenyl methyl ether | C13H16O3 | 详情 | 详情 | |
| (IX) | 49643 | (3R,5R)-5-[[(4-methoxybenzyl)oxy]methyl]tetrahydro-2,3-furandiol | C13H18O5 | 详情 | 详情 | |
| (X) | 49644 | (3R,5R)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-[[(4-methoxybenzyl)oxy]methyl]tetrahydro-2-furanol | C19H32O5Si | 详情 | 详情 | |
| (XI) | 41856 | methyl 2-[bis(2,2,2-trifluoroethoxy)phosphoryl]acetate | 88738-78-7 | C7H9F6O5P | 详情 | 详情 |
| (XII) | 49645 | methyl (Z,4R,6R)-4-[[tert-butyl(dimethyl)silyl]oxy]-6-hydroxy-7-[(4-methoxybenzyl)oxy]-2-heptenoate | C22H36O6Si | 详情 | 详情 | |
| (XIII) | 49646 | methyl (Z,4R,6R)-4-[[tert-butyl(dimethyl)silyl]oxy]-7-[(4-methoxybenzyl)oxy]-6-[(triethylsilyl)oxy]-2-heptenoate | C28H50O6Si2 | 详情 | 详情 | |
| (XIV) | 49647 | (Z,4R,6R)-4-[[tert-butyl(dimethyl)silyl]oxy]-7-[(4-methoxybenzyl)oxy]-6-[(triethylsilyl)oxy]-2-hepten-1-ol | C27H50O5Si2 | 详情 | 详情 | |
| (XV) | 49648 | (Z,4R,6R)-4-[[tert-butyl(dimethyl)silyl]oxy]-7-[(4-methoxybenzyl)oxy]-6-[(triethylsilyl)oxy]-2-heptenal | C27H48O5Si2 | 详情 | 详情 | |
| (XVI) | 49649 | (5R,7R)-5-[(1Z)-4,4-dibromo-1,3-butadienyl]-9,9-diethyl-7-[[(4-methoxybenzyl)oxy]methyl]-2,2,3,3-tetramethyl-4,8-dioxa-3,9-disilaundecane; tert-butyl(dimethyl)silyl (1R,2Z)-5,5-dibromo-1-[(2R)-3-[(4-methoxybenzyl)oxy]-2-[(triethylsilyl)oxy]propyl]-2,4-pentadienyl ether | C28H48Br2O4Si2 | 详情 | 详情 | |
| (XVII) | 49650 | (2R,4R,5Z)-8,8-dibromo-4-[[tert-butyl(dimethyl)silyl]oxy]-2-[(triethylsilyl)oxy]-5,7-octadien-1-ol | C20H40Br2O3Si2 | 详情 | 详情 | |
| (XVIII) | 49651 | (2R,4R,5Z)-8,8-dibromo-4-[[tert-butyl(dimethyl)silyl]oxy]-2-[(triethylsilyl)oxy]-5,7-octadienyl acetate | C22H42Br2O4Si2 | 详情 | 详情 | |
| (XIX) | 49652 | (2R,4R,5Z,7Z)-8-bromo-4-[[tert-butyl(dimethyl)silyl]oxy]-2-[(triethylsilyl)oxy]-5,7-octadienyl acetate | C22H43BrO4Si2 | 详情 | 详情 | |
| (XX) | 49653 | tert-butyl(diphenyl)[[(E)-3-(tributylstannyl)-2-propenyl]oxy]silane; tert-butyl(diphenyl)silyl (E)-3-(tributylstannyl)-2-propenyl ether | C31H50OSiSn | 详情 | 详情 | |
| (XXI) | 49654 | (2R,4R,5Z,7Z,9E)-4-[[tert-butyl(dimethyl)silyl]oxy]-11-[[tert-butyl(diphenyl)silyl]oxy]-2-[(triethylsilyl)oxy]-5,7,9-undecatrienyl acetate | C41H66O5Si3 | 详情 | 详情 | |
| (XXII) | 49655 | (2R,4R,5Z,7Z,9E)-4-[[tert-butyl(dimethyl)silyl]oxy]-11-[[tert-butyl(diphenyl)silyl]oxy]-2-[(triethylsilyl)oxy]-5,7,9-undecatrien-1-ol | C39H64O4Si3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXII)The oxidation of alcohol (XXII) with DMP gives the corresponding aldehyde (XXIII), which is condensed with the lithium salt of diethyl methylphosphonate (XXIV), yielding the beta-hydroxy phosphonate (XXV). The oxidation of the OH group of (XXV) with DMP affords the corresponding ketone (XXVI), which is condensed with the already reported carbaldehyde intermediate (V) by means of potassium tert-butoxide to provide the adduct (XXVII). The methylation of the carbonyl group of (XXVII) with methyl lithium and CeCl3 gives tertiary alcohol (XXVIII), which is selectively monodesilylated with PPTS and ethanol (with simultaneous exchange of the isopropyl acetal group by an ethyl group), yielding the vicinal diol (XXIX). Under carefully controlled conditions, the monosilylation of the diol (XXIX) with Tbdms-OTf gives rise to tertiary silyl ether (XXX), which is treated with HCl to provide the lactol (XXXI). The oxidation of (XXXI) with silver carbonate affords the dihydropyranone (XXXII).
| 【1】 Boger, D.L.; et al.; Total synthesis of fostriecin (CI-920). J Am Chem Soc 2001, 123, 18, 4161. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 49639 | (2R)-6-isopropoxy-3,6-dihydro-2H-pyran-2-carbaldehyde | C9H14O3 | 详情 | 详情 | |
| (XXII) | 49655 | (2R,4R,5Z,7Z,9E)-4-[[tert-butyl(dimethyl)silyl]oxy]-11-[[tert-butyl(diphenyl)silyl]oxy]-2-[(triethylsilyl)oxy]-5,7,9-undecatrien-1-ol | C39H64O4Si3 | 详情 | 详情 | |
| (XXIII) | 49656 | (2R,4R,5Z,7Z,9E)-4-[[tert-butyl(dimethyl)silyl]oxy]-11-[[tert-butyl(diphenyl)silyl]oxy]-2-[(triethylsilyl)oxy]-5,7,9-undecatrienal | C39H62O4Si3 | 详情 | 详情 | |
| (XXIV) | 49657 | [(diethoxyphosphoryl)methyl]lithium | C5H12LiO3P | 详情 | 详情 | |
| (XXV) | 49658 | diethyl (3R,5R,6Z,8Z,10E)-5-[[tert-butyl(dimethyl)silyl]oxy]-12-[[tert-butyl(diphenyl)silyl]oxy]-2-hydroxy-3-[(triethylsilyl)oxy]-6,8,10-dodecatrienylphosphonate | C44H75O7PSi3 | 详情 | 详情 | |
| (XXVI) | 49659 | diethyl (3R,5R,6Z,8Z,10E)-5-[[tert-butyl(dimethyl)silyl]oxy]-12-[[tert-butyl(diphenyl)silyl]oxy]-2-oxo-3-[(triethylsilyl)oxy]-6,8,10-dodecatrienylphosphonate | C44H73O7PSi3 | 详情 | 详情 | |
| (XXVII) | 49660 | (1E,4R,6R,7Z,9Z,11E)-6-[[tert-butyl(dimethyl)silyl]oxy]-13-[[tert-butyl(diphenyl)silyl]oxy]-1-[(2R)-6-isopropoxy-3,6-dihydro-2H-pyran-2-yl]-4-[(triethylsilyl)oxy]-1,7,9,11-tridecatetraen-3-one | C49H76O6Si3 | 详情 | 详情 | |
| (XXVIII) | 49661 | (1E,3R,4R,6R,7Z,9Z,11E)-6-[[tert-butyl(dimethyl)silyl]oxy]-13-[[tert-butyl(diphenyl)silyl]oxy]-1-[(2R)-6-isopropoxy-3,6-dihydro-2H-pyran-2-yl]-3-methyl-4-[(triethylsilyl)oxy]-1,7,9,11-tridecatetraen-3-ol | C50H80O6Si3 | 详情 | 详情 | |
| (XXIX) | 49662 | (1E,3R,4R,6R,7Z,9Z,11E)-6-[[tert-butyl(dimethyl)silyl]oxy]-13-[[tert-butyl(diphenyl)silyl]oxy]-1-[(2R)-6-ethoxy-3,6-dihydro-2H-pyran-2-yl]-3-methyl-1,7,9,11-tridecatetraene-3,4-diol | C43H64O6Si2 | 详情 | 详情 | |
| (XXX) | 49663 | (5R,6R,8R,9Z,11Z,13E)-8-[[tert-butyl(dimethyl)silyl]oxy]-5-[(E)-2-[(2R)-6-ethoxy-3,6-dihydro-2H-pyran-2-yl]ethenyl]-2,2,3,3,5,18,18-heptamethyl-17,17-diphenyl-4,16-dioxa-3,17-disila-9,11,13-nonadecatrien-6-ol | C49H78O6Si3 | 详情 | 详情 | |
| (XXXI) | 49664 | (5R,6R,8R,9Z,11Z,13E)-8-[[tert-butyl(dimethyl)silyl]oxy]-5-[(E)-2-[(2R)-6-hydroxy-3,6-dihydro-2H-pyran-2-yl]ethenyl]-2,2,3,3,5,18,18-heptamethyl-17,17-diphenyl-4,16-dioxa-3,17-disila-9,11,13-nonadecatrien-6-ol | C47H74O6Si3 | 详情 | 详情 | |
| (XXXII) | 49665 | (6R)-6-((1E,3R,4R,6R,7Z,9Z,11E)-3,6-bis[[tert-butyl(dimethyl)silyl]oxy]-13-[[tert-butyl(diphenyl)silyl]oxy]-4-hydroxy-3-methyl-1,7,9,11-tridecatetraenyl)-5,6-dihydro-2H-pyran-2-one | C47H72O6Si3 | 详情 | 详情 |