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【结 构 式】 
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【分子编号】47485 【品名】(3S,4R,6R)-9-(benzyloxy)-6-[(4-methoxybenzyl)oxy]-3-methyl-1-nonen-4-ol 【CA登记号】 |
【 分 子 式 】C25H34O4 【 分 子 量 】398.54256 【元素组成】C 75.34% H 8.6% O 16.06% |
合成路线1
该中间体在本合成路线中的序号：(VII)The reaction of the chiral epoxide (I) with 4-methoxybenzaldehyde (II) by means of NaAl(OMe)3H in THF gives the 1,3-dioxane (III), which is opened by reduction with DIBAL in dichloromethane to yield the chiral benzyl ether (IV). The oxidation of the primary alcohol of (IV) with DMP in dichloromethane affords the corresponding aldehyde (V), which is condensed with the boronate (VI) and S,S-diisopropyl tartrate in toluene to provide the unsaturated alcohol (VII).The protection of (VII) with Tbdps-Cl and imidazole yields the fully protected triol (VIII), which is oxidized at the terminal double bond with 9-BBN in THF to give the primary alcohol (IX). The oxidation of (IX) with DMP in dichloromethane affords the aldehyde (X), which is condensed with methylenetriphenylphosphorane (XI) in THF to provide the terminal olefin (XII). Elimination of the Pmb protecting group of (XII) with DDQ in dichloromethane gives the alcohol (XIII), which is esterified with 2-allyl-6-methoxybenzoic acid (XIV)(obtained by allylation of 2-methoxybenzoic acid (XV) with allyl bromide (XVI), BuLi and MgBr2) by means of DEAD and PPh3 yielding the ester (XVII). The cyclization of (XVII) by means of a metathesis reaction catalyzed by a ruthenium catalyst in refluxing dichloromethane affords the bicyclic lactone (XVIII), which is treated with BBr3 in dichloromethane to provide the dihydroxylated lactone (XIX).
| 【1】 Labrecque, D.; et al.; Enantioselective total synthesis of salicylihalamides A and B. Tetrahedron Lett 2001, 42, 14, 2645. |
| 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) | 47480 | [(2R,3R)-3-[3-(benzyloxy)propyl]oxiranyl]methanol | C13H18O3 | 详情 | 详情 | |
| (II) | 27251 | 4-methoxybenzaldehyde; Anisicaldehyde; p-anisaldehyde | 123-11-5 | C8H8O2 | 详情 | 详情 |
| (III) | 47481 | (4R)-4-[3-(benzyloxy)propyl]-2-(4-methoxyphenyl)-1,3-dioxane; benzyl 3-[(4R)-2-(4-methoxyphenyl)-1,3-dioxan-4-yl]propyl ether | C21H26O4 | 详情 | 详情 | |
| (IV) | 47482 | (3R)-6-(benzyloxy)-3-[(4-methoxybenzyl)oxy]-1-hexanol | C21H28O4 | 详情 | 详情 | |
| (V) | 47483 | (3R)-6-(benzyloxy)-3-[(4-methoxybenzyl)oxy]hexanal | C21H26O4 | 详情 | 详情 | |
| (VI) | 47484 | dimethyl (E)-2-butenylboronate | C6H13BO2 | 详情 | 详情 | |
| (VII) | 47485 | (3S,4R,6R)-9-(benzyloxy)-6-[(4-methoxybenzyl)oxy]-3-methyl-1-nonen-4-ol | C25H34O4 | 详情 | 详情 | |
| (VIII) | 47486 | [((1R,2S)-1-[(2R)-5-(benzyloxy)-2-[(4-methoxybenzyl)oxy]pentyl]-2-methyl-3-butenyl)oxy](tert-butyl)diphenylsilane; benzyl (4R,6R,7S)-6-[[tert-butyl(diphenyl)silyl]oxy]-4-[(4-methoxybenzyl)oxy]-7-methyl-8-nonenyl ether | C41H52O4Si | 详情 | 详情 | |
| (IX) | 47487 | (3S,4R,6R)-9-(benzyloxy)-4-[[tert-butyl(diphenyl)silyl]oxy]-6-[(4-methoxybenzyl)oxy]-3-methyl-1-nonanol | C41H54O5Si | 详情 | 详情 | |
| (X) | 47488 | (3S,4R,6R)-9-(benzyloxy)-4-[[tert-butyl(diphenyl)silyl]oxy]-6-[(4-methoxybenzyl)oxy]-3-methylnonanal | C41H52O5Si | 详情 | 详情 | |
| (XI) | 27301 | methylene(triphenyl)phosphorane | C19H17P | 详情 | 详情 | |
| (XII) | 47489 | [((1R,2S)-1-[(2R)-5-(benzyloxy)-2-[(4-methoxybenzyl)oxy]pentyl]-2-methyl-4-pentenyl)oxy](tert-butyl)diphenylsilane; benzyl (4R,6R,7S)-6-[[tert-butyl(diphenyl)silyl]oxy]-4-[(4-methoxybenzyl)oxy]-7-methyl-9-decenyl ether | C42H54O4Si | 详情 | 详情 | |
| (XIII) | 47490 | (4R,6R,7S)-1-(benzyloxy)-6-[[tert-butyl(diphenyl)silyl]oxy]-7-methyl-9-decen-4-ol | C34H46O3Si | 详情 | 详情 | |
| (XIV) | 13926 | 2-Methoxybenzoic acid; o-Methoxybenzoic Acid | 579-75-9 | C8H8O3 | 详情 | 详情 |
| (XV) | 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
| (XVI) | 47491 | 2-allyl-6-methoxybenzoic acid | C11H12O3 | 详情 | 详情 | |
| (XVII) | 47492 | (1S,3R,4S)-1-[3-(benzyloxy)propyl]-3-[[tert-butyl(diphenyl)silyl]oxy]-4-methyl-6-heptenyl 2-allyl-6-methoxybenzoate | C45H56O5Si | 详情 | 详情 | |
| (XVIII) | 47493 | (3S,5R,6S)-3-[3-(benzyloxy)propyl]-5-[[tert-butyl(diphenyl)silyl]oxy]-14-methoxy-6-methyl-3,4,5,6,7,10-hexahydro-1H-2-benzoxacyclododecin-1-one | C43H52O5Si | 详情 | 详情 | |
| (XIX) | 47494 | (3S,5R,6S)-5-[[tert-butyl(diphenyl)silyl]oxy]-14-hydroxy-3-(3-hydroxypropyl)-6-methyl-3,4,5,6,7,10-hexahydro-1H-2-benzoxacyclododecin-1-one | C35H44O5Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)The reaction of the chiral epoxide (I) with 4-methoxybenzaldehyde (II) by means of NaAl(OMe)3H in THF gives the 1,3-dioxane (III), which is opened by reduction with DIBAL in dichloromethane to yield the chiral benzyl ether (IV). The oxidation of the primary alcohol of (IV) with DMP in dichloromethane affords the corresponding aldehyde (V), which is condensed with the boronate (VI) and S,S-diisopropyl tartrate in toluene to provide the unsaturated alcohol (VII).The protection of (VII) with Tbdps-Cl and imidazole yields the fully protected triol (VIII), which is oxidized at the terminal double bond with 9-BBN in THF to give the primary alcohol (IX). The oxidation of (IX) with DMP in dichloromethane affords the aldehyde (X), which is condensed with methylenetriphenylphosphorane (XI) in THF to provide the terminal olefin (XII). Elimination of the Pmb protecting group of (XII) with DDQ in dichloromethane gives the alcohol (XIII), which is esterified with 2-allyl-6-methoxybenzoic acid (XIV)(obtained by allylation of 2-methoxybenzoic acid (XV) with allyl bromide (XVI), BuLi and MgBr2) by means of DEAD and PPh3 yielding the ester (XVII). The cyclization of (XVII) by means of a metathesis reaction catalyzed by a ruthenium catalyst in refluxing dichloromethane affords the bicyclic lactone (XVIII), which is treated with BBr3 in dichloromethane to provide the dihydroxylated lactone (XIX).
| 【1】 Labrecque, D.; et al.; Enantioselective total synthesis of salicylihalamides A and B. Tetrahedron Lett 2001, 42, 14, 2645. |
| 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) | 47480 | [(2R,3R)-3-[3-(benzyloxy)propyl]oxiranyl]methanol | C13H18O3 | 详情 | 详情 | |
| (II) | 27251 | 4-methoxybenzaldehyde; Anisicaldehyde; p-anisaldehyde | 123-11-5 | C8H8O2 | 详情 | 详情 |
| (III) | 47481 | (4R)-4-[3-(benzyloxy)propyl]-2-(4-methoxyphenyl)-1,3-dioxane; benzyl 3-[(4R)-2-(4-methoxyphenyl)-1,3-dioxan-4-yl]propyl ether | C21H26O4 | 详情 | 详情 | |
| (IV) | 47482 | (3R)-6-(benzyloxy)-3-[(4-methoxybenzyl)oxy]-1-hexanol | C21H28O4 | 详情 | 详情 | |
| (V) | 47483 | (3R)-6-(benzyloxy)-3-[(4-methoxybenzyl)oxy]hexanal | C21H26O4 | 详情 | 详情 | |
| (VI) | 47484 | dimethyl (E)-2-butenylboronate | C6H13BO2 | 详情 | 详情 | |
| (VII) | 47485 | (3S,4R,6R)-9-(benzyloxy)-6-[(4-methoxybenzyl)oxy]-3-methyl-1-nonen-4-ol | C25H34O4 | 详情 | 详情 | |
| (VIII) | 47486 | [((1R,2S)-1-[(2R)-5-(benzyloxy)-2-[(4-methoxybenzyl)oxy]pentyl]-2-methyl-3-butenyl)oxy](tert-butyl)diphenylsilane; benzyl (4R,6R,7S)-6-[[tert-butyl(diphenyl)silyl]oxy]-4-[(4-methoxybenzyl)oxy]-7-methyl-8-nonenyl ether | C41H52O4Si | 详情 | 详情 | |
| (IX) | 47487 | (3S,4R,6R)-9-(benzyloxy)-4-[[tert-butyl(diphenyl)silyl]oxy]-6-[(4-methoxybenzyl)oxy]-3-methyl-1-nonanol | C41H54O5Si | 详情 | 详情 | |
| (X) | 47488 | (3S,4R,6R)-9-(benzyloxy)-4-[[tert-butyl(diphenyl)silyl]oxy]-6-[(4-methoxybenzyl)oxy]-3-methylnonanal | C41H52O5Si | 详情 | 详情 | |
| (XI) | 27301 | methylene(triphenyl)phosphorane | C19H17P | 详情 | 详情 | |
| (XII) | 47489 | [((1R,2S)-1-[(2R)-5-(benzyloxy)-2-[(4-methoxybenzyl)oxy]pentyl]-2-methyl-4-pentenyl)oxy](tert-butyl)diphenylsilane; benzyl (4R,6R,7S)-6-[[tert-butyl(diphenyl)silyl]oxy]-4-[(4-methoxybenzyl)oxy]-7-methyl-9-decenyl ether | C42H54O4Si | 详情 | 详情 | |
| (XIII) | 47490 | (4R,6R,7S)-1-(benzyloxy)-6-[[tert-butyl(diphenyl)silyl]oxy]-7-methyl-9-decen-4-ol | C34H46O3Si | 详情 | 详情 | |
| (XIV) | 13926 | 2-Methoxybenzoic acid; o-Methoxybenzoic Acid | 579-75-9 | C8H8O3 | 详情 | 详情 |
| (XV) | 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
| (XVI) | 47491 | 2-allyl-6-methoxybenzoic acid | C11H12O3 | 详情 | 详情 | |
| (XVII) | 47492 | (1S,3R,4S)-1-[3-(benzyloxy)propyl]-3-[[tert-butyl(diphenyl)silyl]oxy]-4-methyl-6-heptenyl 2-allyl-6-methoxybenzoate | C45H56O5Si | 详情 | 详情 | |
| (XVIII) | 47493 | (3S,5R,6S)-3-[3-(benzyloxy)propyl]-5-[[tert-butyl(diphenyl)silyl]oxy]-14-methoxy-6-methyl-3,4,5,6,7,10-hexahydro-1H-2-benzoxacyclododecin-1-one | C43H52O5Si | 详情 | 详情 | |
| (XIX) | 47494 | (3S,5R,6S)-5-[[tert-butyl(diphenyl)silyl]oxy]-14-hydroxy-3-(3-hydroxypropyl)-6-methyl-3,4,5,6,7,10-hexahydro-1H-2-benzoxacyclododecin-1-one | C35H44O5Si | 详情 | 详情 |