|
【结 构 式】 
|
【分子编号】63121 【品名】(3S,4S,5E)-4-[(4-methoxybenzyl)oxy]-6-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-1-(phenylsulfonyl)-5-hexen-3-ol 【CA登记号】 |
【 分 子 式 】C26H32O6S 【 分 子 量 】472.60248 【元素组成】C 66.08% H 6.82% O 20.31% S 6.78% |
合成路线1
该中间体在本合成路线中的序号：(XXIII)The intermediate phenyl sulfone (XXIII) has been obtained as follows. The reaction of tetrahydropyranyl glycidol (I) with isopropenyl bromide (X) by means of CuCN in THF gives the secondary alcohol (XI), which is treated with allyl bromide (XII) and KH in THF to yield the allyl ether (XIII). A ring closing metathesis reaction with (XIII) catalyzed by a Ru catalyst yields the protected dihydropyran derivative (XIV), which is treated with CSA in methanol to afford the carbinol (XV). The oxidation of (XV) with (COCl)2 and DMSO in dichloromethane provides the carbaldehyde (XVI), which is treated with CBr4 and PPh3 in dichloromethane to give the dibromovinyl derivative (XVII). The condensation of (XVII) with the intermediate aldehyde (VI) by means of BuLi in THF yields the propargyl alcohol derivative (XVIII), which is oxidized with DMP to the corresponding acetylenic ketone (XIX). Alternatively, acetylenic ketone (XIX) can also be obtained by condensation of dibromovinyl derivative (XVII) with the intermediate Weinreb amide (IX) by means of BuLi in THF. The enantioselective reduction of ketone (XIX) with L-Selectride in THF affords the chiral propargyl alcohol (XX), which is reduced with Red-Al and treated with TFA to provide the trans-allylic alcohol (XXI). The reaction of the diol (XXI) with Pmp-CH(OEt)2 and CSA gives the acetal (XXII), which is finally reduced with DIBAL in dichloromethane to yield the intermediate Pmb-protected phenyl sulfone (XXIII).
| 【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 |
|---|---|---|---|---|---|---|
| (I) | 63105 | 2-[(2R)oxiranyloxy]tetrahydro-2H-pyran; (2R)oxiranyl tetrahydro-2H-pyran-2-yl ether | C7H12O3 | 详情 | 详情 | |
| (VI) | 63109 | (2S)-2-[(4-methoxybenzyl)oxy]-4-(phenylsulfonyl)butanal | C18H20O5S | 详情 | 详情 | |
| (IX) | 63111 | (2S)-N-methoxy-2-[(4-methoxybenzyl)oxy]-N-methyl-4-(phenylsulfonyl)butanamide | C20H25NO6S | 详情 | 详情 | |
| (X) | 42375 | 2-bromo-1-propene；2-bromopropene;Isopropenyl bromide;a-Methylvinyl bromide | 557-93-7 | C3H5Br | 详情 | 详情 |
| (XI) | 63112 | (2S)-4-methyl-1-(tetrahydro-2H-pyran-2-yloxy)-4-penten-2-ol | C11H20O3 | 详情 | 详情 | |
| (XII) | 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
| (XIII) | 63113 | allyl (1S)-3-methyl-1-[(tetrahydro-2H-pyran-2-yloxy)methyl]-3-butenyl ether; 2-{[(2S)-2-(allyloxy)-4-methyl-4-pentenyl]oxy}tetrahydro-2H-pyran | C14H24O3 | 详情 | 详情 | |
| (XIV) | 63114 | 2-{[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]methoxy}tetrahydro-2H-pyran; [(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]methyl tetrahydro-2H-pyran-2-yl ether | C12H20O3 | 详情 | 详情 | |
| (XV) | 61173 | [(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]methanol | C7H12O2 | 详情 | 详情 | |
| (XVI) | 61148 | (2S)-4-methyl-3,6-dihydro-2H-pyran-2-carbaldehyde | C7H10O2 | 详情 | 详情 | |
| (XVII) | 63115 | (2S)-2-(2,2-dibromovinyl)-4-methyl-3,6-dihydro-2H-pyran | C8H10Br2O | 详情 | 详情 | |
| (XVIII) | 63116 | (4S)-4-[(4-methoxybenzyl)oxy]-1-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-6-(phenylsulfonyl)-1-hexyn-3-ol | C26H30O6S | 详情 | 详情 | |
| (XIX) | 63117 | (4S)-4-[(4-methoxybenzyl)oxy]-1-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-6-(phenylsulfonyl)-1-hexyn-3-one | C26H28O6S | 详情 | 详情 | |
| (XX) | 63118 | (3S,4S)-4-[(4-methoxybenzyl)oxy]-1-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-6-(phenylsulfonyl)-1-hexyn-3-ol | C26H30O6S | 详情 | 详情 | |
| (XXI) | 63119 | (E,3S,4S)-1-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-6-(phenylsulfonyl)-1-hexene-3,4-diol | C18H24O5S | 详情 | 详情 | |
| (XXII) | 63120 | 2-((4S,5S)-2-(4-methoxyphenyl)-5-{(E)-2-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]ethenyl}-1,3-dioxolan-4-yl)ethyl phenyl sulfone; (2S)-2-((E)-2-{(4S,5S)-2-(4-methoxyphenyl)-5-[2-(phenylsulfonyl)ethyl]-1,3-dioxolan-4-yl}ethenyl)-4-methyl-3,6-dihydro-2H-pyran | C26H30O6S | 详情 | 详情 | |
| (XXIII) | 63121 | (3S,4S,5E)-4-[(4-methoxybenzyl)oxy]-6-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-1-(phenylsulfonyl)-5-hexen-3-ol | C26H32O6S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXIII)The condensation of carbaldehyde (XLVII) with the intermediate Pmb-protected phenyl sulfone (XXIII) by means of BuLi, Ac2O and Na/Hg gives the linear adduct (XLVIII), which is protected at its free OH group by means of DHP and PPTS, and selectively deprotected with TBAF yielding the primary alcohol (XLIX). The oxidation of (XLIX) with DMP affords the acetaldehyde derivative (L), which is condensed with CBr4 and PPh3 to provide the dibromovinyl derivative (LI). The condensation of (LI) with methyl chloroformate (LII) by means of BuLi gives the acetylenic ester (LIII), which is treated with CSA to eliminate the THP protecting group and yield the hydroxy ester (LIV). The hydrolysis of the ester (LIV) with LiOH in THF/water affords the hydroxyacid (LV).
| 【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 |
|---|---|---|---|---|---|---|
| (XXIII) | 63121 | (3S,4S,5E)-4-[(4-methoxybenzyl)oxy]-6-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-1-(phenylsulfonyl)-5-hexen-3-ol | C26H32O6S | 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 | |
| (XLVIII) | 63143 | (1E,3S,4S,6E,8S)-10-{(2S)-3-[(2R,6R)-6-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl}-3-[(4-methoxybenzyl)oxy]-8-(methoxymethoxy)-1-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-1,6,10-undecatrien-4-ol | C44H70O8Si | 详情 | 详情 | |
| (XLIX) | 63144 | 2-{(2R,6R)-6-[(2S,6S,7E,10S,11S,12E)-11-[(4-methoxybenzyl)oxy]-6-(methoxymethoxy)-2-methyl-13-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-4-methylene-10-(tetrahydro-2H-pyran-2-yloxy)-7,12-tridecadienyl]-5,6-dihydro-2H-pyran-2-yl}-1-ethanol | C43H64O9 | 详情 | 详情 | |
| (L) | 63145 | 2-{(2R,6R)-6-[(2S,6S,7E,10S,11S,12E)-11-[(4-methoxybenzyl)oxy]-6-(methoxymethoxy)-2-methyl-13-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-4-methylene-10-(tetrahydro-2H-pyran-2-yloxy)-7,12-tridecadienyl]-5,6-dihydro-2H-pyran-2-yl}acetaldehyde | C43H62O9 | 详情 | 详情 | |
| (LI) | 63146 | (1S,3E,5S)-7-{(2S)-3-[(2R,6R)-6-(3,3-dibromo-2-propenyl)-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl}-1-{(1S,2E)-1-[(4-methoxybenzyl)oxy]-3-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-2-propenyl}-5-(methoxymethoxy)-3,7-octadienyl tetrahydro-2H-pyran-2-yl ether 2-{[(1S,3E,5S)-7-{(2S)-3-[(2R,6R)-6-(3,3-dibromo-2-propenyl)-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl}-1-{(1S,2E)-1-[(4-methoxybenzyl)oxy]-3-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-2-propenyl}-5-(methoxymethoxy)-3,7-octadienyl]oxy}tetrahydro-2H-pyran | C44H62Br2O8 | 详情 | 详情 | |
| (LII) | 16993 | methyl chlorocarbonate;Carbonochloridic acid methyl ester；[(chlorocarbonyl)oxy]methane；methyl chloroformate | 79-22-1 | C2H3ClO2 | 详情 | 详情 |
| (LIII) | 63147 | methyl 4-{(2R,6R)-6-[(2S,6S,7E,10S,11S,12E)-11-[(4-methoxybenzyl)oxy]-6-(methoxymethoxy)-2-methyl-13-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-4-methylene-10-(tetrahydro-2H-pyran-2-yloxy)-7,12-tridecadienyl]-5,6-dihydro-2H-pyran-2-yl}-2-butynoate | C46H64O10 | 详情 | 详情 | |
| (LIV) | 63148 | methyl 4-((2R,6R)-6-{(2S,6S,7E,10S,11S,12E)-10-hydroxy-11-[(4-methoxybenzyl)oxy]-6-(methoxymethoxy)-2-methyl-13-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-4-methylene-7,12-tridecadienyl}-5,6-dihydro-2H-pyran-2-yl)-2-butynoate | C41H56O9 | 详情 | 详情 | |
| (LV) | 63149 | 4-((2R,6R)-6-{(2S,6S,7E,10S,11S,12E)-10-hydroxy-11-[(4-methoxybenzyl)oxy]-6-(methoxymethoxy)-2-methyl-13-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-4-methylene-7,12-tridecadienyl}-5,6-dihydro-2H-pyran-2-yl)-2-butynoic acid | C40H54O9 | 详情 | 详情 |