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【结 构 式】 
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【分子编号】63129 【品名】benzyl (2R)-3-[(2S,6R)-6-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl ether; (2-{(2R,6S)-6-[(2R)-3-(benzyloxy)-2-methylpropyl]-5,6-dihydro-2H-pyran-2-yl}ethoxy)(tert-butyl)dimethylsilane 【CA登记号】 |
【 分 子 式 】C24H40O3Si 【 分 子 量 】404.6653 【元素组成】C 71.24% H 9.96% O 11.86% Si 6.94% |
合成路线1
该中间体在本合成路线中的序号：(XXXVII)The reaction of the chiral diol (XXIV) first with MsCl and TEA, and then with NaCN gives the chiral butyronitrile (XXV), which is reduced with DIBAL in dichloromethane to yield the butyraldehyde (XXVI). The reaction of (XXVI) with allyl tributyl tin (XXVII), (S)-BINOL and Ti(OiPr)4 affords the secondary alcohol (XXVIII), which is condensed with acetal (XXIX) by means of PPTS to provide the diene (XXX). A ring closing metathesis reaction in (XXX) by means of a Ru catalyst gives the dihydropyran derivative (XXXI). Alternatively, the reaction of (XXVIII) with propenoyl chloride (XXXII) by means of TEA gives the diene (XXXIII), which is submitted to a ring closing metathesis reaction as before to yield the dihydropyranone (XXXIV). The reduction of (XXXIV) with DIBAL, followed by treatment with CSA and ethanol affords the dihydropyran derivative (XXXV). The reaction of both acetals (XXXI) or (XXXV) with CH2=CH-O-Tbdms (XXXVI) in the presence of Montmorillonite as Lewis acid, followed by a treatment with NaBH4 provides the dihydropyran (XXXVII) as a single isomer.
| 【1】 Ghosh, A.K.; Wang, Y.; Kim, J.T.; Total synthesis of microtubule-stabilizing agent (-)-laulimalide. J Org Chem 2001, 66, 26, 8973. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXIV) | 63122 | (2R)-3-(benzyloxy)-2-methyl-1-propanol | C11H16O2 | 详情 | 详情 | |
| (XXV) | 63123 | (3R)-4-(benzyloxy)-3-methylbutanenitrile | C12H15NO | 详情 | 详情 | |
| (XXVI) | 63124 | (3R)-4-(benzyloxy)-3-methylbutanal | C12H16O2 | 详情 | 详情 | |
| (XXVII) | 61128 | C4H8 | 详情 | 详情 | ||
| (XXVIII) | 63125 | (4S,6R)-7-(benzyloxy)-6-methyl-1-hepten-4-ol | C15H22O2 | 详情 | 详情 | |
| (XXIX) | 63126 | 3,3-diethoxy-1-propene; 1-ethoxy-2-propenyl ethyl ether | C7H14O2 | 详情 | 详情 | |
| (XXX) | 63127 | 1-[({(2R,4S)-4-[(1-ethoxy-2-propenyl)oxy]-2-methyl-6-heptenyl}oxy)methyl]benzene; benzyl (2R,4S)-4-[(1-ethoxy-2-propenyl)oxy]-2-methyl-6-heptenyl ether | C20H30O3 | 详情 | 详情 | |
| (XXXI) | 63128 | (2S,6R)-2-[(2R)-3-(benzyloxy)-2-methylpropyl]-6-ethoxy-3,6-dihydro-2H-pyran; benzyl (2R)-3-[(2S,6R)-6-ethoxy-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl ether | C18H26O3 | 详情 | 详情 | |
| (XXXII) | 11577 | Acryloyl chloride; Acrylyl chloride;2-Propenoyl chloride | 814-68-6 | C3H3ClO | 详情 | 详情 |
| (XXXIII) | 63130 | (1S)-1-[(2R)-3-(benzyloxy)-2-methylpropyl]-3-butenyl acrylate | C18H24O3 | 详情 | 详情 | |
| (XXXIV) | 63131 | (6S)-6-[(2R)-3-(benzyloxy)-2-methylpropyl]-5,6-dihydro-2H-pyran-2-one | C16H20O3 | 详情 | 详情 | |
| (XXXV) | 63132 | (2S,6S)-2-[(2R)-3-(benzyloxy)-2-methylpropyl]-6-ethoxy-3,6-dihydro-2H-pyran; benzyl (2R)-3-[(2S,6S)-6-ethoxy-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl ether | C18H26O3 | 详情 | 详情 | |
| (XXXVI) | 61133 | tert-butyl(dimethyl)(vinyloxy)silane; tert-butyl(dimethyl)silyl vinyl ether | C8H18OSi | 详情 | 详情 | |
| (XXXVII) | 63129 | benzyl (2R)-3-[(2S,6R)-6-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl ether; (2-{(2R,6S)-6-[(2R)-3-(benzyloxy)-2-methylpropyl]-5,6-dihydro-2H-pyran-2-yl}ethoxy)(tert-butyl)dimethylsilane | C24H40O3Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXXVII)The cleavage of the benzyl ether of (XXXVII) by means of Li/NH3, followed by treatment with I2 and PPh3 gives the iodide derivative (XXXVIII), which is condensed with tetrahydrofuranone (XXXIX) (obtained by reaction of epoxide (XL) with methyl 2-(phenylsulfonyl)acetate (XLI) and NaH) by means of NaH to afford the adduct (XLII). The reductive cleavage of the tetrahydrofuranone (XLII) by means of Red-Al provides the diol (XLIII), which is treated with Ph-COCl and Na/Hg to give the methylene derivative (XLIV). The reaction of (XLIV) with Mom-Cl and DIEA yields the Mom-ether compound (XLV), which is selectively deprotected by means of DDQ to afford the primary alcohol (XLVI). The oxidation of (XLVI) with oxalyl chloride provides the carbaldehyde (XLVII).
| 【1】 Ghosh, A.K.; Wang, Y.; Kim, J.T.; Total synthesis of microtubule-stabilizing agent (-)-laulimalide. J Org Chem 2001, 66, 26, 8973. |
| 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) | 63129 | benzyl (2R)-3-[(2S,6R)-6-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl ether; (2-{(2R,6S)-6-[(2R)-3-(benzyloxy)-2-methylpropyl]-5,6-dihydro-2H-pyran-2-yl}ethoxy)(tert-butyl)dimethylsilane | C24H40O3Si | 详情 | 详情 | |
| (XXXVIII) | 63133 | tert-butyl(2-{(2R,6S)-6-[(2R)-3-iodo-2-methylpropyl]-5,6-dihydro-2H-pyran-2-yl}ethoxy)dimethylsilane; tert-butyl(dimethyl)silyl 2-{(2R,6S)-6-[(2R)-3-iodo-2-methylpropyl]-5,6-dihydro-2H-pyran-2-yl}ethyl ether | C17H33IO2Si | 详情 | 详情 | |
| (XXXIX) | 63134 | (5S)-5-{[(4-methoxybenzyl)oxy]methyl}-3-(phenylsulfonyl)dihydro-2(3H)-furanone | C19H20O6S | 详情 | 详情 | |
| (XL) | 63135 | 4-methoxybenzyl (2R)oxiranylmethyl ether; (2R)-2-{[(4-methoxybenzyl)oxy]methyl}oxirane | C11H14O3 | 详情 | 详情 | |
| (XLI) | 63136 | methyl 2-(phenylsulfonyl)acetate | C9H10O4S | 详情 | 详情 | |
| (XLII) | 63137 | (5S)-3-{(2R)-3-[(2R,6R)-6-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl}-5-{[(4-methoxybenzyl)oxy]methyl}-3-(phenylsulfonyl)dihydro-2(3H)-furanone | C36H52O8SSi | 详情 | 详情 | |
| (XLIII) | 63138 | (4S)-2-{(2R)-3-[(2R,6R)-6-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl}-5-[(4-methoxybenzyl)oxy]-2-(phenylsulfonyl)-1,4-pentanediol | C36H56O8SSi | 详情 | 详情 | |
| (XLIV) | 63139 | (2S)-4-{(2S)-3-[(2R,6R)-6-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl}-1-[(4-methoxybenzyl)oxy]-4-penten-2-ol | C30H50O5Si | 详情 | 详情 | |
| (XLV) | 63140 | tert-butyl(dimethyl)silyl 2-((2R,6R)-6-{(2S)-4-[(2S)-3-[(4-methoxybenzyl)oxy]-2-(methoxymethoxy)propyl]-2-methyl-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)ethyl ether; tert-butyl[2-((2R,6R)-6-{(2S)-4-[(2S)-3-[(4-methoxybenzyl)oxy]-2-(methoxymethoxy)propyl]-2-methyl-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)ethoxy]dimethylsilane | C32H54O6Si | 详情 | 详情 | |
| (XLVI) | 63141 | (2S)-4-{(2S)-3-[(2R,6R)-6-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl}-2-(methoxymethoxy)-4-penten-1-ol | C24H46O5Si | 详情 | 详情 | |
| (XLVII) | 63142 | (2S)-4-{(2S)-3-[(2R,6R)-6-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl}-2-(methoxymethoxy)-4-pentenal | C24H44O5Si | 详情 | 详情 |