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【结 构 式】 
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【分子编号】55210 【品名】{(Z,2R,3S)-2-[(tert-butoxycarbonyl)amino]-3-methoxy-3-methylhexylidene}(4-methoxybenzyl)ammoniumolate 【CA登记号】 |
【 分 子 式 】C21H34N2O5 【 分 子 量 】394.51144 【元素组成】C 63.94% H 8.69% N 7.1% O 20.28% |
合成路线1
该中间体在本合成路线中的序号：(LXVIII)In a different procedure, addition of the allyl Grignard reagent (LX) to the N-methoxy amide (LIX), provided ketone (LXI). Subsequent addition of methylmagnesium chloride to (LXI) led to the tertiary alcohol (LXII), which was converted to the methyl ether (LXIII) by alkylation with iodomethane and NaH. Acetonide (LXIII) hydrolysis with p-toluenesulfonic acid in MeOH gave the N-Boc amino alcohol (LXIV). The olefin double bond of (LXIV) was then hydrogenated over Pd/C to the propyl derivative (LXV). Oxidation of alcohol (LXV) under modified Swern conditions furnished aldehyde (LXVI). This was then condensed with p-methoxybenzyl hydroxylamine (LXVII), leading to the nitrone (LXVIII).
| 【1】 Hanessian, S.; et al.; Total synthesis of A-315675: A potent inhibitor of influenza neuraminidase. J Am Chem Soc 2002, 124, 17, 4716. |
| 【2】 Inhibitors of neuraminidases. WO 0128996 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (LIX) | 55202 | tert-butyl (4R)-4-{[methoxy(methyl)amino]carbonyl}-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | C13H24N2O5 | 详情 | 详情 | |
| (LX) | 53638 | allyl(chloro)magnesium | 2622-05-1 | C3H5ClMg | 详情 | 详情 |
| (LXI) | 55203 | tert-butyl (4R)-4-(3-butenoyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | C14H23NO4 | 详情 | 详情 | |
| (LXII) | 55204 | tert-butyl (4R)-4-[(1S)-1-hydroxy-1-methyl-3-butenyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | C15H27NO4 | 详情 | 详情 | |
| (LXIII) | 55205 | tert-butyl (4R)-4-[(1S)-1-methoxy-1-methyl-3-butenyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | C16H29NO4 | 详情 | 详情 | |
| (LXIV) | 55206 | tert-butyl (1R,2S)-1-(hydroxymethyl)-2-methoxy-2-methyl-4-pentenylcarbamate | C13H25NO4 | 详情 | 详情 | |
| (LXV) | 55207 | tert-butyl (1R,2S)-1-(hydroxymethyl)-2-methoxy-2-methylpentylcarbamate | C13H27NO4 | 详情 | 详情 | |
| (LXVI) | 55208 | tert-butyl (1S,2S)-1-formyl-2-methoxy-2-methylpentylcarbamate | C13H25NO4 | 详情 | 详情 | |
| (LXVII) | 55209 | 1-[(hydroxyamino)methyl]-4-methoxybenzene; N-(4-methoxybenzyl)hydroxylamine | C8H11NO2 | 详情 | 详情 | |
| (LXVIII) | 55210 | {(Z,2R,3S)-2-[(tert-butoxycarbonyl)amino]-3-methoxy-3-methylhexylidene}(4-methoxybenzyl)ammoniumolate | C21H34N2O5 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(LXVIII)Addition of the lithium anion of tert-butyl propiolate (LXIX) to nitrone (LXVIII) in the presence of BF3·Et2O gave adduct (LXX). Reduction of the hydroxylamine (LXX), with concomitant cyclization by treatment with Zn and HOAc, produced pyrrolidone (LXXI). The propenyl group of (LXXII) was introduced by conjugate addition of the corresponding organocuprate reagent to the unsaturated lactam (LXXI). Acidic Boc group cleavage in (LXXII), followed by acetylation of the resultant amine, afforded acetamide (LXXIII). Oxidative cleavage of the p-methoxybenzyl group of (LXXIII) using ammonium cerium nitrate gave pyrrolidone (LXXIV), which was further protected as the N-Boc derivative (LXXV). Introduction of the cyano group in (LXXV) as in the above methods led to the common precursor (XXXVII).
| 【1】 Hanessian, S.; et al.; Total synthesis of A-315675: A potent inhibitor of influenza neuraminidase. J Am Chem Soc 2002, 124, 17, 4716. |
| 【2】 Inhibitors of neuraminidases. WO 0128996 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXVII) | 55180 | tert-butyl (2R,3S,5R)-2-[(1R,2S)-1-(acetylamino)-2-methoxy-2-methylpentyl]-5-cyano-3-[(Z)-1-propenyl]-1-pyrrolidinecarboxylate | C22H37N3O4 | 详情 | 详情 | |
| (LXVIII) | 55210 | {(Z,2R,3S)-2-[(tert-butoxycarbonyl)amino]-3-methoxy-3-methylhexylidene}(4-methoxybenzyl)ammoniumolate | C21H34N2O5 | 详情 | 详情 | |
| (LXIX) | 28925 | tert-butyl propiolate | 13831-03-3 | C7H10O2 | 详情 | 详情 |
| (LXX) | 55211 | tert-butyl (5R,6S)-5-[(tert-butoxycarbonyl)amino]-4-[hydroxy(4-methoxybenzyl)amino]-6-methoxy-6-methyl-2-nonynoate | C28H44N2O7 | 详情 | 详情 | |
| (LXXI) | 55212 | tert-butyl (1R,2S)-2-methoxy-1-[(2R)-1-(4-methoxybenzyl)-5-oxo-2,5-dihydro-1H-pyrrol-2-yl]-2-methylpentylcarbamate | C24H36N2O5 | 详情 | 详情 | |
| (LXXII) | 55213 | tert-butyl (1R,2S)-2-methoxy-1-{(2R,3S)-1-(4-methoxybenzyl)-5-oxo-3-[(Z)-1-propenyl]pyrrolidinyl}-2-methylpentylcarbamate | C27H42N2O5 | 详情 | 详情 | |
| (LXXIII) | 55214 | N-((1R,2S)-2-methoxy-1-{(2R,3S)-1-(4-methoxybenzyl)-5-oxo-3-[(Z)-1-propenyl]pyrrolidinyl}-2-methylpentyl)acetamide | C24H36N2O4 | 详情 | 详情 | |
| (LXXIV) | 55215 | N-((1R,2S)-2-methoxy-2-methyl-1-{(2R,3S)-5-oxo-3-[(Z)-1-propenyl]pyrrolidinyl}pentyl)acetamide | C16H28N2O3 | 详情 | 详情 | |
| (LXXV) | 55216 | tert-butyl (2R,3S)-2-[(1R,2S)-1-(acetylamino)-2-methoxy-2-methylpentyl]-5-oxo-3-[(Z)-1-propenyl]-1-pyrrolidinecarboxylate | C21H36N2O5 | 详情 | 详情 |