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【结 构 式】 
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【分子编号】61140 【品名】2-((2R,6S)-6-{(2S)-2-methyl-4-[(trimethylsilyl)methyl]-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)acetaldehyde 【CA登记号】 |
【 分 子 式 】C17H30O2Si 【 分 子 量 】294.5095 【元素组成】C 69.33% H 10.27% O 10.87% Si 9.54% |
合成路线1
该中间体在本合成路线中的序号：(XVII)The synthesis of the dihydropyranyl acetaldehyde intermediate (XVII) has been obtained as follows: The reduction of the pentanedioic acid monoethyl ester (I) with BH3 gives the hydroxyester (II), which is oxidized with DMP to yield the aldehyde (III). The reaction of (III) with the chiral borane (IV) affords the 5-hydroxyoctenoic ester (V), which is treated with dimethylamine to provide the corresponding amide (VI). The reaction of (VI) with propenal diethylacetal (VII) gives ether (VIII), which is submitted to a ring closing metathesis reaction catalyzed by a Ru catalyst to yield the dihydropyran derivative (IX). The reaction of (IX) with tert-butyldimethylsilyloxy ethylene (X) catalyzed by LiClO4 affords the dihydropyranyl acetaldehyde (XI), which is reduced with NaBH4 and protected with Tes-Cl to provide the butyramide (XII). The reaction of (XII) with MeLi gives the pentanone (XIII), which is treated with Ph-NTf2 and KHMDS to yield the enol triflate (XIV). The reaction of (XIV) with Tms-CH2-MgCl affords the methylene derivative (XV), which is selectively desilylated with K2CO3 to provide the dihdyropyranyl ethanol compound (XVI). Finally, this compound is oxidized with DMP to obtain the target dihydropyranyl acetaldehyde intermediate (XVII).
| 【1】 Ahmed, A.; Hoegenauer, E.K.; Enev, V.S.; Hanbauer, M.; Kaehlig, H.; Ohler, E.; Mulzer, J.; Total synthesis of the microtubule stabilizing antitumor agent laulimalide and some nonnatural analogues: The power of Sharpless' asymmetric epoxidation. J. Org. Chem. 2003, 68, 8, 3026. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 61304 | Trimethylsilylmethylmagnesium Chloride; (Trimethylsilyl)methylmagnesium chloride Solution; Chloro[(trimethylsilyl)methyl]magnesium; (TRIMETHYLSILYLMETHYL)MAGNESIUM CHLORIDE; (TRIMETHYLSILYL)METHYLMAGNESIUM CHL. SOL | 13170-43-9 | C4H11ClMgSi | 详情 | 详情 |
| (I) | 61124 | (3R)-3-methyl-5-oxo-5-propoxypentanoic acid | C9H16O4 | 详情 | 详情 | |
| (II) | 61125 | propyl (3R)-5-hydroxy-3-methylpentanoate | C9H18O3 | 详情 | 详情 | |
| (III) | 61126 | propyl (3R)-3-methyl-5-oxopentanoate | C9H16O3 | 详情 | 详情 | |
| (IV) | 61128 | C4H8 | 详情 | 详情 | ||
| (V) | 61127 | propyl (3R,5S)-5-hydroxy-3-methyl-7-octenoate | C12H22O3 | 详情 | 详情 | |
| (VI) | 61129 | (3R,5S)-5-hydroxy-N,N,3-trimethyl-7-octenamide | C11H21NO2 | 详情 | 详情 | |
| (VII) | 61131 | 1-propoxy-2-propenyl propyl ether; 3,3-dipropoxy-1-propene | C9H18O2 | 详情 | 详情 | |
| (VIII) | 61130 | (3R,5S)-N,N,3-trimethyl-5-[(1-propoxy-2-propenyl)oxy]-7-octenamide | C17H31NO3 | 详情 | 详情 | |
| (IX) | 61132 | (3R)-N,N,3-trimethyl-4-[(2S)-6-propoxy-3,6-dihydro-2H-pyran-2-yl]butanamide | C15H27NO3 | 详情 | 详情 | |
| (X) | 61133 | tert-butyl(dimethyl)(vinyloxy)silane; tert-butyl(dimethyl)silyl vinyl ether | C8H18OSi | 详情 | 详情 | |
| (XI) | 61134 | (3R)-N,N,3-trimethyl-4-[(2S,6R)-6-(2-oxoethyl)-3,6-dihydro-2H-pyran-2-yl]butanamide | C14H23NO3 | 详情 | 详情 | |
| (XII) | 61135 | (3R)-N,N,3-trimethyl-4-((2S,6R)-6-{2-[(triethylsilyl)oxy]ethyl}-3,6-dihydro-2H-pyran-2-yl)butanamide | C20H39NO3Si | 详情 | 详情 | |
| (XIII) | 61136 | (4R)-4-methyl-5-((2S,6R)-6-{2-[(triethylsilyl)oxy]ethyl}-3,6-dihydro-2H-pyran-2-yl)-2-pentanone | C19H36O3Si | 详情 | 详情 | |
| (XIV) | 61137 | 1-[(2R)-2-methyl-3-((2S,6R)-6-{2-[(triethylsilyl)oxy]ethyl}-3,6-dihydro-2H-pyran-2-yl)propyl]vinyl trifluoromethanesulfonate | C20H35F3O5SSi | 详情 | 详情 | |
| (XV) | 61138 | 2-((2R,6S)-6-{(2S)-2-methyl-4-[(trimethylsilyl)methyl]-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)ethyl triethylsilyl ether; trimethyl{2-[(2S)-2-methyl-3-((2S,6R)-6-{2-[(triethylsilyl)oxy]ethyl}-3,6-dihydro-2H-pyran-2-yl)propyl]-2-propenyl}silane | C23H46O2Si2 | 详情 | 详情 | |
| (XVI) | 61139 | 2-((2R,6S)-6-{(2S)-2-methyl-4-[(trimethylsilyl)methyl]-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)-1-ethanol | C17H32O2Si | 详情 | 详情 | |
| (XVII) | 61140 | 2-((2R,6S)-6-{(2S)-2-methyl-4-[(trimethylsilyl)methyl]-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)acetaldehyde | C17H30O2Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XVII)The condensation of the dihydropyranyl acetaldehyde intermediate (XVII) with the phosphonate (XXXVII) by means of KHMDS gives the open chain adduct (XXXVIII), which is cyclized by means of EtAlCl2 in dichloromethane to yield the macrolactone (XXXIX). The oxidation of the secondary OH group of (XXXIX) by means of DMP affords the ketone (XL), which is treated with TsOH in chloroform to provide the alcohol (XLI). The deprotection of the Mom-protecting group by means of Me2BBr in dichloromethane gives the dihydroxylated macrolactone (XLII), which is finally epoxidized by means of (+)-DIPT, t-BuOOH and Ti(i-PrO)4 to yield the target Laulimalide.
| 【1】 Ahmed, A.; Hoegenauer, E.K.; Enev, V.S.; Hanbauer, M.; Kaehlig, H.; Ohler, E.; Mulzer, J.; Total synthesis of the microtubule stabilizing antitumor agent laulimalide and some nonnatural analogues: The power of Sharpless' asymmetric epoxidation. J. Org. Chem. 2003, 68, 8, 3026. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVII) | 61140 | 2-((2R,6S)-6-{(2S)-2-methyl-4-[(trimethylsilyl)methyl]-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)acetaldehyde | C17H30O2Si | 详情 | 详情 | |
| (XXXVII) | 61158 | (1S,2S,3E)-1-{(E)-3-[(4R,6R)-4,6-dimethyl-1,3-dioxan-2-yl]-2-propenyl}-2-(methoxymethoxy)-4-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-3-butenyl 2-[bis(2,2,2-trifluoroethoxy)phosphoryl]acetate | C27H39F6O10P | 详情 | 详情 | |
| (XXXVIII) | 61159 | (1S,2S,3E)-1-{(E)-3-[(4R,6R)-4,6-dimethyl-1,3-dioxan-2-yl]-2-propenyl}-2-(methoxymethoxy)-4-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-3-butenyl (Z)-4-((2R,6S)-6-{(2S)-2-methyl-4-[(trimethylsilyl)methyl]-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)-2-buten | C40H64O8Si | 详情 | 详情 | |
| (XXXIX) | 61160 | (1R,7S,11S,15S,17S)-11-{[(1R,2S)-2-hydroxy-1-methylpropyl]oxy}-7-{(1S,2E)-1-(methoxymethoxy)-3-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-2-propenyl}-15-methyl-13-methylene-6,21-dioxabicyclo[15.3.1]henicosa-3,9,19-trien-5-one | C36H54O8 | 详情 | 详情 | |
| (XL) | 61161 | (1R,7S,11S,15S,17S)-7-{(1S,2E)-1-(methoxymethoxy)-3-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-2-propenyl}-15-methyl-13-methylene-11-{[(1R)-1-methyl-2-oxopropyl]oxy}-6,21-dioxabicyclo[15.3.1]henicosa-3,9,19-trien-5-one | C36H52O8 | 详情 | 详情 | |
| (XLI) | 61162 | +(1R,7S,11S,15S,17S)-11-hydroxy-7-{(1S,2E)-1-(methoxymethoxy)-3-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-2-propenyl}-15-methyl-13-methylene-6,21-dioxabicyclo[15.3.1]henicosa-3,9,19-trien-5-one | C32H46O7 | 详情 | 详情 | |
| (XLII) | 61163 | (1R,7S,11S,15S,17S)-11-hydroxy-7-{(1S,2E)-1-hydroxy-3-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-2-propenyl}-15-methyl-13-methylene-6,21-dioxabicyclo[15.3.1]henicosa-3,9,19-trien-5-one | C30H42O6 | 详情 | 详情 |