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【结 构 式】 
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【分子编号】37560 【品名】[((1S,2E)-3-[(1S,2R,3aS,6aS)-2-[[tert-butyl(dimethyl)silyl]oxy]-5-[(E)-6-(tetrahydro-2H-pyran-2-yloxy)hexylidene]octahydro-1-pentalenyl]-1-pentyl-2-propenyl)oxy](tert-butyl)dimethylsilane; 6-[(3aS,4S,5R,6aS)-5-[[tert-butyl(dimethyl)silyl]oxy]-4-((E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-1-octenyl)hexahydro-2(1H)-pentalenylidene]hexyl tetrahydro-2H-pyran-2-yl ether 【CA登记号】 |
【 分 子 式 】C39H74O4Si2 【 分 子 量 】663.18516 【元素组成】C 70.63% H 11.25% O 9.65% Si 8.47% |
合成路线1
该中间体在本合成路线中的序号：(LXIV)The reaction of 7-oxotricyclo[4.2.0.0(2.4)]octane-3-endo-carboxaldehyde neopentylglycol acetal (LIII) with dimethylsulfonium methylide (G) gives the spiroepoxide (LIV), which by isomerization with LiI in THF yields the tricyclononanone (LV). The reduction of (LV) with NaBH4 in ethanol, followed by acetylation with acetic anhydride in pyridine affords the tricyclic acetate (LVI), which is treated with formic acid to eliminate the acetalic residue and form the free aldehyde (LVII). The Wittig reaction of (LVII) with triphenylhexylidenephosphorane (LVIII) affords the tricyclic acetate (LIX), which is hydrolyzed with base and oxidized with Jones reagent to yield the tricyclic ketone (LX). The oxidation of the double bond of (LX) with 0sO4 gives the diol (LXI), which submitted successively to: triethyl orthopropionate (H) in pyridine, to anhydrous formic acid, to aqueous methanolic K2CO3 and to sodium metaperiodate, is converted into the previously obtained dihydroxyketone (XII). This compound can be used in the preceding syntheses or protected with dimethyltert-butylsilyl chloride to afford the bis(silyl) ether (LXII), which by reaction with the sulfoximine (LXIII), and then with AlHg is converted into the protected trialcohol (LXIV).
| 【1】 Morton, D.R.Jr.; DE 2904655 . |
| 【2】 Brokaw, F.C.; Morton, D.R.Jr.; Total synthesis of 6a-carboprostaglandin I2 and related isomers. J Org Chem 1979, 44, 16, 2880-87. |
| 【3】 Castaner, J.; Hillier, K.; Carbacyclin. Drugs Fut 1981, 6, 12, 753. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (G) | 16180 | Dimethyl(methylene)-lambda(4)-sulfane; Dimethylsulfonium-methylide | C3H8S | 详情 | 详情 | |
| (H) | 37557 | 1-ethoxypropyl ethyl ether; 1,1-diethoxypropane | 4744-08-5 | C7H16O2 | 详情 | 详情 |
| (XII) | 37504 | (3aS,4S,5R,6aR)-5-hydroxy-4-[(E,3S)-3-hydroxy-1-octenyl]hexahydro-2(1H)-pentalenone | C16H26O3 | 详情 | 详情 | |
| (LIII) | 37548 | (1R,2S,4S,6S)-3-(5,5-dimethyl-1,3-dioxan-2-yl)tricyclo[4.2.0.0(2,4)]octan-7-one | C14H20O3 | 详情 | 详情 | |
| (LIV) | 37549 | C15H22O3 | 详情 | 详情 | ||
| (LV) | 37550 | (1aR,1bS,4aR,5aS)-1-(5,5-dimethyl-1,3-dioxan-2-yl)octahydro-3H-cyclopropa[a]pentalen-3-one | C15H22O3 | 详情 | 详情 | |
| (LVI) | 37551 | (1aR,1bS,4aR,5aS)-1-(5,5-dimethyl-1,3-dioxan-2-yl)octahydro-1H-cyclopropa[a]pentalen-3-yl acetate | C17H26O4 | 详情 | 详情 | |
| (LVII) | 37552 | (1aR,1bS,4aR,5aS)-1-formyloctahydro-1H-cyclopropa[a]pentalen-3-yl acetate | C12H16O3 | 详情 | 详情 | |
| (LVIII) | 37553 | hexylidene(triphenyl)phosphorane | C24H27P | 详情 | 详情 | |
| (LIX) | 37554 | (1aS,1bS,4aR,5aS)-1-[(E)-1-heptenyl]octahydro-1H-cyclopropa[a]pentalen-3-yl acetate | C18H28O2 | 详情 | 详情 | |
| (LX) | 37555 | (1aS,1bS,4aR,5aS)-1-[(E)-1-heptenyl]octahydro-3H-cyclopropa[a]pentalen-3-one | C16H24O | 详情 | 详情 | |
| (LXI) | 37556 | (1aR,1bS,4aR,5aS)-1-[(1R,2S)-1,2-dihydroxyheptyl]octahydro-3H-cyclopropa[a]pentalen-3-one | C16H26O3 | 详情 | 详情 | |
| (LXII) | 37558 | (3aS,4S,5R,6aR)-5-[[tert-butyl(dimethyl)silyl]oxy]-4-((E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-1-octenyl)hexahydro-2(1H)-pentalenone | C28H54O3Si2 | 详情 | 详情 | |
| (LXIII) | 37559 | bromo[1-[methyl(phenyl)sulfonimidoyl]-6-(tetrahydro-2H-pyran-2-yloxy)hexyl]magnesium | C18H28BrMgNO3S | 详情 | 详情 | |
| (LXIV) | 37560 | [((1S,2E)-3-[(1S,2R,3aS,6aS)-2-[[tert-butyl(dimethyl)silyl]oxy]-5-[(E)-6-(tetrahydro-2H-pyran-2-yloxy)hexylidene]octahydro-1-pentalenyl]-1-pentyl-2-propenyl)oxy](tert-butyl)dimethylsilane; 6-[(3aS,4S,5R,6aS)-5-[[tert-butyl(dimethyl)silyl]oxy]-4-((E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-1-octenyl)hexahydro-2(1H)-pentalenylidene]hexyl tetrahydro-2H-pyran-2-yl ether | C39H74O4Si2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(LXIV)Selective hydrolysis of the silyl groups of (LXIV), and acetylation with acetic anhydride yields the diacetate (LXV), which is hydrolyzed again selectively with acetic acid, and oxidized with Jones reagent to afford the carbacyclin diacetate (LXVI) Finally, this compound is hydrolyzed with base.
| 【1】 Morton, D.R.Jr.; DE 2904655 . |
| 【2】 Brokaw, F.C.; Morton, D.R.Jr.; Total synthesis of 6a-carboprostaglandin I2 and related isomers. J Org Chem 1979, 44, 16, 2880-87. |
| 【3】 Castaner, J.; Hillier, K.; Carbacyclin. Drugs Fut 1981, 6, 12, 753. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (LXIV) | 37560 | [((1S,2E)-3-[(1S,2R,3aS,6aS)-2-[[tert-butyl(dimethyl)silyl]oxy]-5-[(E)-6-(tetrahydro-2H-pyran-2-yloxy)hexylidene]octahydro-1-pentalenyl]-1-pentyl-2-propenyl)oxy](tert-butyl)dimethylsilane; 6-[(3aS,4S,5R,6aS)-5-[[tert-butyl(dimethyl)silyl]oxy]-4-((E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-1-octenyl)hexahydro-2(1H)-pentalenylidene]hexyl tetrahydro-2H-pyran-2-yl ether | C39H74O4Si2 | 详情 | 详情 | |
| (LXV) | 37561 | (1S,2R,3aS,6aS)-1-[(E,3S)-3-(acetoxy)-1-octenyl]-5-[(E)-6-(tetrahydro-2H-pyran-2-yloxy)hexylidene]octahydro-2-pentalenyl acetate | C31H50O6 | 详情 | 详情 | |
| (LXVI) | 37562 | 5-[(3aS,4S,5R,6aS)-5-(acetoxy)-4-[(E,3S)-3-(acetoxy)-1-octenyl]hexahydro-2(1H)-pentalenylidene]pentanoic acid | C25H38O6 | 详情 | 详情 |