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【结 构 式】 
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【分子编号】13772 【品名】[(1R,2R,3R)-3-Allyl-2-([[tert-butyl(dimethyl)silyl]oxy]methyl)-4-methylenecyclopentyl]methyl tetrahydro-2H-pyran-2-yl ether; ([(1R,2R,5R)-2-Allyl-3-methylene-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]methoxy)(tert-butyl)dimethylsilane 【CA登记号】 |
【 分 子 式 】C22H40O3Si 【 分 子 量 】380.6433 【元素组成】C 69.42% H 10.59% O 12.61% Si 7.38% |
合成路线1
该中间体在本合成路线中的序号：(XLIX)5) The unsaturated pentanoic acid methyl ester derivative (XLV) obtained in scheme 16133803a can also be obtained as follows: The reaction of lactol (II) with methyltriphenylphosphonium bromide and t-BuOK in THF, followed by oxidation with PCC in dichloromethane gives the allyl ketone (XLVIII), which is methylenated with Zn/CH2Br2/TiCl4 to yield compound (XLIX). The reaction of (XLIX) with disiamylborane (DSB) and H2O2 hydroxylates the two double bonds, affording compound (L) with two primary hydroxy groups, which are oxidized with oxalyl chloride to the corresponding (LI) with two aldehyde groups. This compound cyclizes to the bicyclic hydroxyaldehyde (LII), which is dehydrated with dibenzylammonium trifluoroacetate to the unsaturated bicyclic aldehyde (LIII). The condensation of (LIII) with 3-carboxypropyltriphenylphosphonium bromide (LIV) by means of t-BuOK in THF followed by methylation with diazomethane gives the bicyclic dienoic ester (LV), which is then selectively reduced to the previously described intermediate (XLV).
| 【1】 Sodeoka, M.; Shibasaki, M.; The highly potent carbon analog of prostacyclin. Chem Lett 1984, 4, 4, 579-82. |
| 【2】 Graul, A.; Leeson, P.; Castaner, J.; Clinprost. Drugs Fut 1997, 22, 6, 608. |
| 【3】 Shibasaki, M.; Mase, T.; Sodeoka, M.; Ogawa, Y. (Sagami Chemical Research Center); Bicyclo[3.3.0]octane deriv. and preparation thereof. EP 0134153 . |
| 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) | 13714 | Methyl 5-chloro-2-hydroxybenzoate; Methyl 5-chlorosalicylate | 4068-78-4 | C8H7ClO3 | 详情 | 详情 |
| (II) | 13725 | (3aR,4S,5R,6aS)-4-([[tert-Butyl(dimethyl)silyl]oxy]methyl)-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]hexahydro-2H-cyclopenta[b]furan-2-ol | C20H38O5Si | 详情 | 详情 | |
| (XLV) | 13768 | methyl 5-[(3aS,5R,6R,6aS)-6-([[tert-butyl(dimethyl)silyl]oxy]methyl)-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1,3a,4,5,6,6a-hexahydro-2-pentalenyl]pentanoate | C27H48O5Si | 详情 | 详情 | |
| (XLVIII) | 13771 | (2R,3S,4R)-2-Allyl-3-([[tert-butyl(dimethyl)silyl]oxy]methyl)-4-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentanone | C21H38O4Si | 详情 | 详情 | |
| (XLIX) | 13772 | [(1R,2R,3R)-3-Allyl-2-([[tert-butyl(dimethyl)silyl]oxy]methyl)-4-methylenecyclopentyl]methyl tetrahydro-2H-pyran-2-yl ether; ([(1R,2R,5R)-2-Allyl-3-methylene-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]methoxy)(tert-butyl)dimethylsilane | C22H40O3Si | 详情 | 详情 | |
| (L) | 13773 | 3-[(1S,2R,3R,5S)-2-([[tert-Butyl(dimethyl)silyl]oxy]methyl)-5-(hydroxymethyl)-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]-1-propanol | C22H44O5Si | 详情 | 详情 | |
| (LI) | 13774 | (1S,2R,3R,4R)-3-([[tert-Butyl(dimethyl)silyl]oxy]methyl)-2-(3-oxopropyl)-4-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentanecarbaldehyde | C22H40O5Si | 详情 | 详情 | |
| (LII) | 13775 | (1R,3aR,4R,5R,6aS)-4-([[tert-Butyl(dimethyl)silyl]oxy]methyl)-1-hydroxy-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]octahydro-2-pentalenecarbaldehyde | C22H40O5Si | 详情 | 详情 | |
| (LIII) | 13776 | (3aS,5R,6R,6aS)-6-([[tert-Butyl(dimethyl)silyl]oxy]methyl)-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1,3a,4,5,6,6a-hexahydro-2-pentalenecarbaldehyde | C22H38O4Si | 详情 | 详情 | |
| (LIV) | 13777 | (3-Carboxypropyl)phosphonium bromide | C4H10BrO2P | 详情 | 详情 | |
| (LV) | 13778 | methyl (Z)-5-[(3aS,5R,6R,6aS)-6-([[tert-butyl(dimethyl)silyl]oxy]methyl)-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1,3a,4,5,6,6a-hexahydro-2-pentalenyl]-4-pentenoate | C27H46O5Si | 详情 | 详情 |