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【结 构 式】 
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【分子编号】48417 【品名】3-((2S,5S)-5-[2-[(4R,6R)-2-([(2S,3R,4R,4aS,6R,7R,8aS)-7-[[tert-butyl(dimethyl)silyl]oxy]-6-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3-[(4-methoxybenzyl)oxy]-4-methyloctahydropyrano[3,2-b]pyran-2-yl]methyl)-4-methyl-3-methylene-1,2-oxazinan-6-yl]ethyl]-4-methylenetetrahydro-2-furanyl)propyl 2,2-dimethylpropanoate 【CA登记号】 |
【 分 子 式 】C52H89NO10Si2 【 分 子 量 】944.4504 【元素组成】C 66.13% H 9.5% N 1.48% O 16.94% Si 5.95% |
合成路线1
该中间体在本合成路线中的序号：(VIII)Dess-Martin oxidation of alcohol (I) in CH2Cl2 yields aldehyde (II), which is then subjected to a Horner-Emmons reaction with phosphonate (III) in THF in the presence of NaH to provide compound (IV). Enone (IV) is then converted into intermediate (V) by first conjugate reduction by the Stryker reagent, reduction with NaBH4 in MeOH of the resulting saturated ketone, separation of the two possible diastereomers obtained and final mesylation by means of Ms2O and Et3N. Dess-Martin oxidation of the primary alcohol (VI) affords aldehyde (VII), which is then coupled to mesylate (V) by means of NiCl2-CrCl2 in DMF/THF. The resulting product is subjected to cyclization by means of KH in DME to furnish tetrahydropyran derivative (VIII). Reduction of (VIII) with LiAlH4 in Et2O yields alcohol (IX), which is then oxidized by the Dess Martin reagent to give aldehyde (X). Coupling of (X) with compound (XI) by means of NiCl2-CrCl2 in DMF/THF affords ketone (XII).
| 【1】 Aicher, T.D.; et al.; Total synthesis of halichondrin B and norhalichondrin B. J Am Chem Soc 1992, 114, 8, 3162. |
| 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) | 48410 | 3-[(2S,5R)-5-(hydroxymethyl)-4-methylenetetrahydro-2-furanyl]propyl pivalate | C14H24O4 | 详情 | 详情 | |
| (II) | 48411 | 3-[(2S,5R)-5-formyl-4-methylenetetrahydro-2-furanyl]propyl pivalate | C14H22O4 | 详情 | 详情 | |
| (III) | 48412 | dimethyl (4R)-5-iodo-4-methyl-2-oxo-5-hexenylphosphonate | C9H16IO4P | 详情 | 详情 | |
| (IV) | 48413 | 3-[(2S,5S)-5-[(1Z,5R)-6-iodo-5-methyl-3-oxo-1,6-heptadienyl]-4-methylenetetrahydro-2-furanyl]propyl pivalate | C21H31IO4 | 详情 | 详情 | |
| (V) | 48414 | 3-[(2S,5S)-5-((3R,5R)-6-iodo-5-methyl-3-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-6-heptenyl)-4-methylenetetrahydro-2-furanyl]propyl pivalate | C24H41IO4S | 详情 | 详情 | |
| (VI) | 48415 | 2-[(2S,3R,4R,4aS,6R,7R,8aS)-7-[[tert-butyl(dimethyl)silyl]oxy]-6-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3-[(4-methoxybenzyl)oxy]-4-methyloctahydropyrano[3,2-b]pyran-2-yl]-1-ethanol | C32H58O7Si2 | 详情 | 详情 | |
| (VII) | 48416 | 2-[(2S,3R,4R,4aS,6R,7R,8aS)-7-[[tert-butyl(dimethyl)silyl]oxy]-6-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3-[(4-methoxybenzyl)oxy]-4-methyloctahydropyrano[3,2-b]pyran-2-yl]acetaldehyde | C32H56O7Si2 | 详情 | 详情 | |
| (VIII) | 48417 | 3-((2S,5S)-5-[2-[(4R,6R)-2-([(2S,3R,4R,4aS,6R,7R,8aS)-7-[[tert-butyl(dimethyl)silyl]oxy]-6-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3-[(4-methoxybenzyl)oxy]-4-methyloctahydropyrano[3,2-b]pyran-2-yl]methyl)-4-methyl-3-methylene-1,2-oxazinan-6-yl]ethyl]-4-methylenetetrahydro-2-furanyl)propyl 2,2-dimethylpropanoate | C52H89NO10Si2 | 详情 | 详情 | |
| (IX) | 48418 | 3-((2S,5S)-5-[2-[(4R,6R)-2-([(2S,3R,4R,4aS,6R,7R,8aS)-7-[[tert-butyl(dimethyl)silyl]oxy]-6-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3-[(4-methoxybenzyl)oxy]-4-methyloctahydropyrano[3,2-b]pyran-2-yl]methyl)-4-methyl-3-methylene-1,2-oxazinan-6-yl]ethyl]-4-methylenetetrahydro-2-furanyl)-1-propanol | C47H81NO9Si2 | 详情 | 详情 | |
| (X) | 48419 | 3-((2S,5S)-5-[2-[(4R,6R)-2-([(2S,3R,4R,4aS,6R,7R,8aS)-7-[[tert-butyl(dimethyl)silyl]oxy]-6-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3-[(4-methoxybenzyl)oxy]-4-methyloctahydropyrano[3,2-b]pyran-2-yl]methyl)-4-methyl-3-methylene-1,2-oxazinan-6-yl]ethyl]-4-methylenetetrahydro-2-furanyl)propanal | C47H79NO9Si2 | 详情 | 详情 | |
| (XI) | 48420 | methyl 2-[(2R,4aS,6S,7R,8S,8aS)-7,8-bis[[tert-butyl(dimethyl)silyl]oxy]-6-((1S,2E)-1-[[tert-butyl(dimethyl)silyl]oxy]-3-iodo-2-propenyl)octahydropyrano[3,2-b]pyran-2-yl]acetate | C32H63IO7Si3 | 详情 | 详情 | |
| (XII) | 48421 | C79H141NO16Si5 | 详情 | 详情 |