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【结 构 式】 
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【分子编号】64620 【品名】ethyl (E,4S)-4-{[tert-butyl(dimethyl)silyl]oxy}-6-(phenylsulfonyl)-2-hexenoate 【CA登记号】 |
【 分 子 式 】C20H32O5SSi 【 分 子 量 】412.62258 【元素组成】C 58.22% H 7.82% O 19.39% S 7.77% Si 6.81% |
合成路线1
该中间体在本合成路线中的序号：(XXXII)Advanced intermediate phosphonium salt (XLI). The protection of (R)(+)-glycidol (XXV) with Pmb-Cl and NaH gives the benzyl ether (XXVI). Which is condensed with methyl phenyl sulfone (XXVII) by means of BuLi in THF/HMPA to yield the secondary alcohol (XXVIII). The reaction of (XXVIII) with Tbdms-OTf and lutidine affords the silyl ether (XXIX) (3), which is converted into the aldehyde (XXX) by debenzylation with DDQ, followed by oxidation with DMP. The condensation of (XXX) with phosphorane (XXXI) in refluxing benzene gives the unsaturated ester (XXXII), which is reduced with DIBAL in dichloromethane and protected with Ph-CH2Br and NaH to yield the benzyl ether (XXXIII). The condensation of sulfone (XXXIII) with the iodomethyl intermediate (XXIV) by means of BuLi in THF/HMPA affords the adduct (XXXIV), which is desulfurized by reaction with BuLi, diiodomethane and isopropylmagnesium chloride to provide the methylene compound (XXXV). The elimination of the benzyl protecting group of (XXXV) by means of LiDBB, followed by oxidation with DMP gives the carbaldehyde (XXXVI), which is condensed with CH2=PPh3 in THF to yield compound (XXXVII) (2).
| 【1】 Smith, A.B. III; Lin, Q.; Pettit, G.R.; Chapuis, G.R.; Chapuis, J.-C.; Schmidt, J.M.; Synthesis and in vitro cancer cell growth inhibitory activity of monocyclic model cpds. containing spongistatin triene side-chains. Bioorg Med Chem Lett 1998, 8, 6, 567. |
| 【2】 Smith, A.B. III; Lin, Q.; Doughty, V.A.; Zhuang, L.; McBriar, M.D.; Kerns, J.K.; Brook, C.S.; Murase, N.; Nakayama, K.; The spongistatins: Architecturally complex natural products - Part two: Synthesis of the C(29-51) subunit, fragment assembly, and final elaboration to (+)-spongistatin 2. Angew Chem. Int Ed 2001, 40, 1, 196. |
| 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) | 64616 | tert-butyl[((2R,4S,5S,6R)-6-(4-{[tert-butyl(diphenyl)silyl]oxy}butyl)-2-{(S)-{(2R,3S,4R,5R,6S)-6-(iodomethyl)-3-methyl-4,5-bis[(triethylsilyl)oxy]tetrahydro-2H-pyran-2-yl}[(triethylsilyl)oxy]methyl}-2-methoxy-5-methyltetrahydro-2H-pyran-4-yl)oxy]dimethylsilane; tert-butyl(dimethyl)silyl (2R,4S,5S,6R)-6-(4-{[tert-butyl(diphenyl)silyl]oxy}butyl)-2-{(S)-{(2R,3S,4R,5R,6S)-6-(iodomethyl)-3-methyl-4,5-bis[(triethylsilyl)oxy]tetrahydro-2H-pyran-2-yl}[(triethylsilyl)oxy]methyl}-2-methoxy-5-methyltetrahydro-2H-pyran-4-yl ether | C59H109IO8Si5 | 详情 | 详情 | |
| (XXV) | 19241 | (2S)oxiranylmethanol | 60456-23-7 | C3H6O2 | 详情 | 详情 |
| (XXVI) | 63135 | 4-methoxybenzyl (2R)oxiranylmethyl ether; (2R)-2-{[(4-methoxybenzyl)oxy]methyl}oxirane | C11H14O3 | 详情 | 详情 | |
| (XXVII) | 23622 | methyl phenyl sulfone; methyl(dioxo)phenyl-lambda(6)-sulfane | 3112-85-4 | C7H8O2S | 详情 | 详情 |
| (XXVIII) | 64617 | (2S)-1-[(4-methoxybenzyl)oxy]-4-(phenylsulfonyl)-2-butanol | C18H22O5S | 详情 | 详情 | |
| (XXIX) | 64618 | (3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-[(4-methoxybenzyl)oxy]butyl phenyl sulfone; tert-butyl{[(1S)-1-{[(4-methoxybenzyl)oxy]methyl}-3-(phenylsulfonyl)propyl]oxy}dimethylsilane | C24H36O5SSi | 详情 | 详情 | |
| (XXX) | 64619 | (2S)-2-{[tert-butyl(dimethyl)silyl]oxy}-4-(phenylsulfonyl)butanal | C16H26O4SSi | 详情 | 详情 | |
| (XXXI) | 14182 | ethyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate; (Carbethoxymethylene)triphenylphosphorane | 1099-45-2 | C22H21O2P | 详情 | 详情 |
| (XXXII) | 64620 | ethyl (E,4S)-4-{[tert-butyl(dimethyl)silyl]oxy}-6-(phenylsulfonyl)-2-hexenoate | C20H32O5SSi | 详情 | 详情 | |
| (XXXIII) | 64621 | (3S,4E)-6-(benzyloxy)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-hexenyl phenyl sulfone; ({(1S,2E)-4-(benzyloxy)-1-[2-(phenylsulfonyl)ethyl]-2-butenyl}oxy)(tert-butyl)dimethylsilane | C25H36O4SSi | 详情 | 详情 | |
| (XXXIV) | 64622 | (3S,4E)-6-(benzyloxy)-3-{[tert-butyl(dimethyl)silyl]oxy}-1-({(2R,3R,4R,5S,6R)-6-{(S)-[(2R,4S,5S,6R)-4-{[tert-butyl(dimethyl)silyl]oxy}-6-(4-{[tert-butyl(diphenyl)silyl]oxy}butyl)-2-methoxy-5-methyltetrahydro-2H-pyran-2-yl][(triethylsilyl)oxy]methyl}-5-methyl-3,4-bis[(triethylsilyl)oxy]tetrahydro-2H-pyran-2-yl}methyl)-4-hexenyl phenyl sulfone; ({(1S,2E)-4-(benzyloxy)-1-[3-{(2R,3R,4R,5S,6R)-6-{(S)-[(2R,4S,5S,6R)-4-{[tert-butyl(dimethyl)silyl]oxy}-6-(4-{[tert-butyl(diphenyl)silyl]oxy}butyl)-2-methoxy-5-methyltetrahydro-2H-pyran-2-yl][(triethylsilyl)oxy]methyl}-5-methyl-3,4-bis[(triethylsilyl)oxy]tetrahydro-2H-pyran-2-yl}-2-(phenylsulfonyl)propyl]-2-butenyl}oxy)(tert-butyl)dimethylsilane | C84H144O12SSi6 | 详情 | 详情 | |
| (XXXV) | 64623 | ({(1S,2E)-4-(benzyloxy)-1-[2-({(2R,3R,4R,5S,6R)-6-{(S)-[(2R,4S,5S,6R)-4-{[tert-butyl(dimethyl)silyl]oxy}-6-(4-{[tert-butyl(diphenyl)silyl]oxy}butyl)-2-methoxy-5-methyltetrahydro-2H-pyran-2-yl][(triethylsilyl)oxy]methyl}-5-methyl-3,4-bis[(triethylsilyl)oxy]tetrahydro-2H-pyran-2-yl}methyl)-2-propenyl]-2-butenyl}oxy)(tert-butyl)dimethylsilane; benzyl (2E,4S)-4-{[tert-butyl(dimethyl)silyl]oxy}-6-({(2R,3R,4R,5S,6R)-6-{(S)-[(2R,4S,5S,6R)-4-{[tert-butyl(dimethyl)silyl]oxy}-6-(4-{[tert-butyl(diphenyl)silyl]oxy}butyl)-2-methoxy-5-methyltetrahydro-2H-pyran-2-yl][(triethylsilyl)oxy]methyl}-5-methyl-3,4-bis[(triethylsilyl)oxy]tetrahydro-2H-pyran-2-yl}methyl)-2,6-heptadienyl ether | C79H140O10Si6 | 详情 | 详情 | |
| (XXXVI) | 64624 | (2E,4S)-4-{[tert-butyl(dimethyl)silyl]oxy}-6-({(2R,3R,4R,5S,6R)-6-{(S)-[(2R,4S,5S,6R)-4-{[tert-butyl(dimethyl)silyl]oxy}-6-(4-{[tert-butyl(diphenyl)silyl]oxy}butyl)-2-methoxy-5-methyltetrahydro-2H-pyran-2-yl][(triethylsilyl)oxy]methyl}-5-methyl-3,4-bis[(triethylsilyl)oxy]tetrahydro-2H-pyran-2-yl}methyl)-2,6-heptadienal | C72H132O10Si6 | 详情 | 详情 | |
| (XXXVII) | 64625 | tert-butyl({(1S,2E)-1-[2-({(2R,3R,4R,5S,6R)-6-{(S)-[(2R,4S,5S,6R)-4-{[tert-butyl(dimethyl)silyl]oxy}-6-(4-{[tert-butyl(diphenyl)silyl]oxy}butyl)-2-methoxy-5-methyltetrahydro-2H-pyran-2-yl][(triethylsilyl)oxy]methyl}-5-methyl-3,4-bis[(triethylsilyl)oxy]tetrahydro-2H-pyran-2-yl}methyl)-2-propenyl]-2,4-pentadienyl}oxy)dimethylsilane; tert-butyl(dimethyl)silyl (1S,2E)-1-[2-({(2R,3R,4R,5S,6R)-6-{(S)-[(2R,4S,5S,6R)-4-{[tert-butyl(dimethyl)silyl]oxy}-6-(4-{[tert-butyl(diphenyl)silyl]oxy}butyl)-2-methoxy-5-methyltetrahydro-2H-pyran-2-yl][(triethylsilyl)oxy]methyl}-5-methyl-3,4-bis[(triethylsilyl)oxy]tetrahydro-2H-pyran-2-yl}methyl)-2-propenyl]-2,4-pentadienyl ether | C73H134O9Si6 | 详情 | 详情 |