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【结 构 式】 
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【分子编号】21528 【品名】(1R,2R,3E)-1-butyl-2-[[tert-butyl(dimethyl)silyl]oxy]-1-methyl-4-(tributylstannyl)-3-butenyl methyl ether 【CA登记号】 |
【 分 子 式 】C28H60O2SiSn 【 分 子 量 】575.5787 【元素组成】C 58.43% H 10.51% O 5.56% Si 4.88% Sn 20.62% |
合成路线1
该中间体在本合成路线中的序号：(II)The reaction of 3(R)-(tert-butyldimethylsilyloxy)-4(R)-methoxy-4(R)-methyl-1-(tributylstannyl)-1(E)-octene (II) with butyllithium, cuprous iodide and tributylphosphine gives an intermediate copper derivative which is condensed first with 4(R)-(tert-butyldimethylsilyloxy)-2-cyclopentenone (I) and then with methyl 6-formylhexanoate (III) to give the 7-hydroxy PGE1 derivative (IV). The dehydration of (IV) with mesyl chloride yields the unsaturated PGE compound (V), which is reduced with tributystannyl hydride and finally deprotected with acetic acid in THF. The starting products (I) and (II) are obtained as follows: 1) The oxidation of cyclopentadiene (VI) gives 2-cyclopentene-1,4-diol (VII), which is acetylated to the diacetate (VIII). Selective hydrolysis of (VIII) yields (1S, 4R)-4-hydroxy-2-cyclopentenyl acetate (IX), which is protected with tert-butyldimethylsilyl chloride to the protected acetate (X). Partial hydrolysis of (X) affords the semiprotected alcohol (XI), which is finally oxidized to the cyclopentenone (I).
| 【1】 Kolb, M.; Van Hijfte, L.; Ireland, R.E.; A highly convergent synthesis of mexiprostil: 16(R) 16-methoxy 16-methyl PGE1 methyl ester. Tetrahedron Lett 1988, 29, 51, 6769. |
| 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) | 13805 | (4R)-4-[[tert-Butyl(dimethyl)silyl]oxy]-2-cyclopenten-1-one | C11H20O2Si | 详情 | 详情 | |
| (II) | 21528 | (1R,2R,3E)-1-butyl-2-[[tert-butyl(dimethyl)silyl]oxy]-1-methyl-4-(tributylstannyl)-3-butenyl methyl ether | C28H60O2SiSn | 详情 | 详情 | |
| (III) | 21529 | methyl 7-oxoheptanoate | 35376-00-2 | C8H14O3 | 详情 | 详情 |
| (IV) | 21530 | methyl 7-[(2R,3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-((E,3R,4R)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methoxy-4-methyl-1-octenyl)-5-oxocyclopentyl]-7-hydroxyheptanoate | C35H68O7Si2 | 详情 | 详情 | |
| (V) | 21531 | methyl 7-[(2R,3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-((E,3R,4R)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methoxy-4-methyl-1-octenyl)-5-oxocyclopentylidene]heptanoate | C35H66O6Si2 | 详情 | 详情 | |
| (VI) | 11183 | 1,3-Cyclopentadiene | C5H6 | 详情 | 详情 | |
| (VII) | 21533 | 4-cyclopentene-1,3-diol | C5H8O2 | 详情 | 详情 | |
| (VIII) | 21534 | 4-(acetoxy)-2-cyclopenten-1-yl acetate | C9H12O4 | 详情 | 详情 | |
| (IX) | 21535 | (1R,4R)-4-hydroxy-2-cyclopenten-1-yl acetate | C7H10O3 | 详情 | 详情 | |
| (X) | 21536 | (1R,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-cyclopenten-1-yl acetate | C13H24O3Si | 详情 | 详情 | |
| (XI) | 21537 | (1R,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-cyclopenten-1-ol | C11H22O2Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)2) The epoxidation of nerol (XII) with tert-butyl peroxide and titanium isopropoxide gives the epoxide (XIII), which is benzylated with benzyl bromide to the protected epoxide (XIV). A stereo- and regioselective cleavage of the epoxide (XIV) with methanol yields the methoxy hydroxy derivative (XV), which is ozonolyzed in methanol dichloromethane to the aldehyde (XVI). The Wittig condensation of (XVI) with triphenylmethylphosphonium bromide and potassium tert-butoxide affords the methylene alcohol (XVII), which is protected with tert-butyldimethylsilyl chloride as before to give silyl derivative (XVIII). The hydrogenation of (XVIII) with H2 over Pd in ethyl acetate yields the saturated alcohol (XIX), which is oxidized with oxalyl chloride in DMSO to the aldehyde (XX).The reaction of (XX) with tetrabromomethane and triphenylphosphine affords the dibromovinyl compound (XXI), which by reaction with butyllithium in THF is converted into the acetylene (XXII). Finally, this compound is treated with tributylstannyl hydride and azobisisobutyronitrile to give the stannyl derivative (II).
| 【1】 Kolb, M.; Van Hijfte, L.; Ireland, R.E.; A highly convergent synthesis of mexiprostil: 16(R) 16-methoxy 16-methyl PGE1 methyl ester. Tetrahedron Lett 1988, 29, 51, 6769. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 30484 | Methyl(triphenyl)phosphonium bromide | 1779-49-3 | C19H18BrP | 详情 | 详情 | |
| (A) | 12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 |
| (II) | 21528 | (1R,2R,3E)-1-butyl-2-[[tert-butyl(dimethyl)silyl]oxy]-1-methyl-4-(tributylstannyl)-3-butenyl methyl ether | C28H60O2SiSn | 详情 | 详情 | |
| (XII) | 21538 | (2Z)-3,7-dimethyl-2,6-octadien-1-ol | 106-25-2 | C10H18O | 详情 | 详情 |
| (XIII) | 21539 | [(2R,3S)-3-methyl-3-(4-methyl-3-pentenyl)oxiranyl]methanol | C10H18O2 | 详情 | 详情 | |
| (XIV) | 21540 | (2S,3R)-3-[(benzyloxy)methyl]-2-methyl-2-(4-methyl-3-pentenyl)oxirane | C17H24O2 | 详情 | 详情 | |
| (XV) | 21541 | (2R,3R)-1-(benzyloxy)-3-methoxy-3,7-dimethyl-6-octen-2-ol | C18H28O3 | 详情 | 详情 | |
| (XVI) | 21542 | (4R,5R)-6-(benzyloxy)-5-hydroxy-4-methoxy-4-methylhexanal | C15H22O4 | 详情 | 详情 | |
| (XVII) | 21543 | (2R,3R)-1-(benzyloxy)-3-methoxy-3-methyl-6-hepten-2-ol | C16H24O3 | 详情 | 详情 | |
| (XVIII) | 21544 | ([(1R,2R)-1-[(benzyloxy)methyl]-2-methoxy-2-methyl-5-hexenyl]oxy)(tert-butyl)dimethylsilane | C22H38O3Si | 详情 | 详情 | |
| (XIX) | 21545 | (2R,3R)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methoxy-3-methyl-1-heptanol | C15H34O3Si | 详情 | 详情 | |
| (XX) | 21546 | (3R,4R)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methoxy-4-methyloctanal | C16H34O3Si | 详情 | 详情 | |
| (XXI) | 21547 | tert-butyl(dimethyl)silyl (1R)-3,3-dibromo-1-[(1R)-1-methoxy-1-methylpentyl]-2-propenyl ether | C16H32Br2O2Si | 详情 | 详情 | |
| (XXII) | 21548 | (1R,2R)-1-butyl-2-[[tert-butyl(dimethyl)silyl]oxy]-1-methyl-3-butynyl methyl ether | C16H32O2Si | 详情 | 详情 |