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【结 构 式】 
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【分子编号】64737 【品名】(2-{5-methyl-2-[4-(methyloxy)phenyl]-1,3-dioxan-4-yl}propyl)(triphenyl)phosphonium iodide 【CA登记号】 |
【 分 子 式 】C33H36IO3P 【 分 子 量 】638.525272 【元素组成】C 62.07% H 5.68% I 19.87% O 7.52% P 4.85% |
合成路线1
该中间体在本合成路线中的序号：(X)Protection of (S)-3-hydroxy-2-methylpropionic acid methyl ester (I) as the corresponding silyl ether, followed by reduction with DIBAL provides the aldehyde (II). Diastereoselective aldol condensation of (II) with the chiral N-propionyl oxazolidinone (III) in the presence of dibutylboron triflate leads to adduct (IV), which is then reduced with LiBH4 to give the diol (V). The diol (V) is protected as the cyclic ketal (VII) by treatment with anisaldehyde dimethylacetal (VI) in the presence of pyridinium p-toluenesulfonate (PPTS). Desilylation of (VII) using tetrabutylammonium fluoride yields the alcohol (VIII). Subsequent iodination of (VIII) with I2/PPh3, followed by displacement of alkyl iodide (IX) with PPh3 in refluxing benzene, furnishes the phosphonium salt (X).
| 【1】 Choy, N.; Shin, Y.; Nguyen, P.Q.; Curran, D.P.; Balachandran, R.; Madiraju, C.; Day, B.W.; Simplified discodermolide analogues: Synthesis and biological evaluation of 4-epi-7-dehydroxy-14,16-didemethyl-(+)-discodermolides as microtubule-stabilizing agents. J Med Chem 2003, 46, 14, 2846. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 17128 | Methyl (2S)-3-hydroxy-2-methylpropanoate | 72657-23-9 | C5H10O3 | 详情 | 详情 |
| (II) | 42624 | (2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methylpropanal | C10H22O2Si | 详情 | 详情 | |
| (III) | 25713 | (4S)-4-benzyl-3-propionyl-1,3-oxazolidin-2-one | C13H15NO3 | 详情 | 详情 | |
| (IV) | 64732 | 3-(5-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-3-hydroxy-2,4-dimethylpentanoyl)-4-(phenylmethyl)-1,3-oxazolidin-2-one | C23H37NO5Si | 详情 | 详情 | |
| (V) | 64733 | 5-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-2,4-dimethyl-1,3-pentanediol | C13H30O3Si | 详情 | 详情 | |
| (VI) | 26485 | 1-(dimethoxymethyl)-4-methoxybenzene | 2186-92-7 | C10H14O3 | 详情 | 详情 |
| (VII) | 64734 | (1,1-dimethylethyl)(dimethyl)[(2-{5-methyl-2-[4-(methyloxy)phenyl]-1,3-dioxan-4-yl}propyl)oxy]silane; (1,1-dimethylethyl)(dimethyl)silyl 2-{5-methyl-2-[4-(methyloxy)phenyl]-1,3-dioxan-4-yl}propyl ether | C21H36O4Si | 详情 | 详情 | |
| (VIII) | 64735 | 2-{5-methyl-2-[4-(methyloxy)phenyl]-1,3-dioxan-4-yl}-1-propanol | C15H22O4 | 详情 | 详情 | |
| (IX) | 64736 | 4-(2-iodo-1-methylethyl)-5-methyl-2-[4-(methyloxy)phenyl]-1,3-dioxane; 4-[4-(2-iodo-1-methylethyl)-5-methyl-1,3-dioxan-2-yl]phenyl methyl ether | C15H21IO3 | 详情 | 详情 | |
| (X) | 64737 | (2-{5-methyl-2-[4-(methyloxy)phenyl]-1,3-dioxan-4-yl}propyl)(triphenyl)phosphonium iodide | C33H36IO3P | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(X)The lactone (XVIII) is reduced by means of DIBAL to the corresponding lactol (XIX). Treatment of (XIX) with MeOH and PPTS generates an anomeric mixture of methyl ketals, from which isomer (XX) can be separated by column chromatography. Catalytic hydrogenolysis of the p-methoxybenzyl moiety of (XX) leads to alcohol (XXI), which is further converted into aldehyde (XXII) by Dess-Martin oxidation. Wittig condensation between aldehyde (XXII) and phosphonium salt (X) affords the cis-olefin (XXIII). Reductive opening of the cyclic acetal (XXIII) utilizing DIBAL produces the mono-benzylated diol (XXIV), which is then oxidized to aldehyde (XXV) under Swern conditions.
| 【1】 Choy, N.; Shin, Y.; Nguyen, P.Q.; Curran, D.P.; Balachandran, R.; Madiraju, C.; Day, B.W.; Simplified discodermolide analogues: Synthesis and biological evaluation of 4-epi-7-dehydroxy-14,16-didemethyl-(+)-discodermolides as microtubule-stabilizing agents. J Med Chem 2003, 46, 14, 2846. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 64737 | (2-{5-methyl-2-[4-(methyloxy)phenyl]-1,3-dioxan-4-yl}propyl)(triphenyl)phosphonium iodide | C33H36IO3P | 详情 | 详情 | |
| (XVIII) | 64744 | 3,5-dimethyl-4-{[(methyloxy)methyl]oxy}-6-[3-({[4-(methyloxy)phenyl]methyl}oxy)propyl]tetrahydro-2H-pyran-2-one | C20H30O6 | 详情 | 详情 | |
| (XIX) | 64745 | 3,5-dimethyl-4-{[(methyloxy)methyl]oxy}-6-[3-({[4-(methyloxy)phenyl]methyl}oxy)propyl]tetrahydro-2H-pyran-2-ol | C20H32O6 | 详情 | 详情 | |
| (XX) | 64746 | 3,5-dimethyl-4-{[(methyloxy)methyl]oxy}-6-[3-({[4-(methyloxy)phenyl]methyl}oxy)propyl]tetrahydro-2H-pyran-2-yl methyl ether; 3,5-dimethyl-2-(methyloxy)-4-{[(methyloxy)methyl]oxy}-6-[3-({[4-(methyloxy)phenyl]methyl}oxy)propyl]tetrahydro-2H-pyran | C21H34O6 | 详情 | 详情 | |
| (XXI) | 64747 | 3-(3,5-dimethyl-6-(methyloxy)-4-{[(methyloxy)methyl]oxy}tetrahydro-2H-pyran-2-yl)-1-propanol | C13H26O5 | 详情 | 详情 | |
| (XXII) | 64748 | 3-(3,5-dimethyl-6-(methyloxy)-4-{[(methyloxy)methyl]oxy}tetrahydro-2H-pyran-2-yl)propanal | C13H24O5 | 详情 | 详情 | |
| (XXIII) | 64749 | 3,5-dimethyl-6-(5-{5-methyl-2-[4-(methyloxy)phenyl]-1,3-dioxan-4-yl}-3-hexenyl)-4-{[(methyloxy)methyl]oxy}tetrahydro-2H-pyran-2-yl methyl ether; 4-[5-(3,5-dimethyl-6-(methyloxy)-4-{[(methyloxy)methyl]oxy}tetrahydro-2H-pyran-2-yl)-1-methyl-2-pentenyl]-5-methyl-2-[4-(methyloxy)phenyl]-1,3-dioxane | C28H44O7 | 详情 | 详情 | |
| (XXIV) | 64750 | 8-(3,5-dimethyl-6-(methyloxy)-4-{[(methyloxy)methyl]oxy}tetrahydro-2H-pyran-2-yl)-2,4-dimethyl-3-({[4-(methyloxy)phenyl]methyl}oxy)-5-octen-1-ol | C28H46O7 | 详情 | 详情 | |
| (XXV) | 64751 | 8-(3,5-dimethyl-6-(methyloxy)-4-{[(methyloxy)methyl]oxy}tetrahydro-2H-pyran-2-yl)-2,4-dimethyl-3-({[4-(methyloxy)phenyl]methyl}oxy)-5-octenal | C28H44O7 | 详情 | 详情 |