【结 构 式】 |
【分子编号】11473 【品名】(2S)-2-[(1S)-1-(4-Methoxybenzyl)-2-propenyl]oxirane; Methyl 4-[(2S)-2-[(2S)oxiranyl]-3-butenyl]phenyl ether 【CA登记号】 |
【 分 子 式 】C13H16O2 【 分 子 量 】204.26884 【元素组成】C 76.44% H 7.9% O 15.67% |
合成路线1
该中间体在本合成路线中的序号:(XXXV)2) (2R,3S,5S(2'S,4'R))-5-(2-(iodomethyl)tetrahydrofuran-4-yl)-5-(4-methoxy benzyloxy)-2-methyl-3-(triisopropylsilyloxy)pentanal (XXXII). The regioselective reduction of methyl 5-(4-methoxybenzyloxy)-3-oxopentanoate (XXI) with H2 over Ru2Cl4((S)-BINAP)2(C2H5)3N in methanol gives the 3(S)-hydroxy derivative (XXII), which is condensed with ally bromide (XXIII) by means of lithium diisopropylamide THF-HMPA to yield the ally derivative (XXIV). The reduction of (XXIV) with LiAlH4 in THF affords the diol (XXV), which is cyclized to the ketal (XXVI) by means of DDQ in dichloromethane. The reaction of (XXVI) first with N-iodosuccinimide (NIS) and then with diisobutylaluminum hydride affords (3S(2'S,4'R))-3-(2-iodomethyl)tetrahydrofuran-4-yl)-3-(4-methoxybenzyl)-1-propanol (XXVII), which is oxidized to the corresponding aldehyde (XXVIII) by means of oxalyl chloride in dichloromethane. The condensation of (XXVIII) with 2(E)-butenyltriphenylstannane (XXIX) by means of boron trifluoride ethearate in dichloromethane gives the alcohol (XXX), which is protected with TIPS trifluoromethanesulfonate in dichloromethane yielding the fully protected diol (XXXI). Finally, the double bond of (XXXI) is oxidized with ozone in methanol - dichloromethane yielding the second building fragment (XXXII).
【1】 Smith, D.B.; Schreiber, S.L.; Ragan, J.A.; Uehling, D.E.; Nakatsuka, M.; Sammakia, T.; Total synthesis of FK506 and an FKBP probe reagent, (C8,C9-13C2)-FK5. J Am Chem Soc 1990, 112, 14, 5583. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(XXI) | 11461 | methyl 6-(4-methoxyphenyl)-3-oxohexanoate | C14H18O4 | 详情 | 详情 | |
(XXII) | 11462 | methyl (3S)-3-hydroxy-6-(4-methoxyphenyl)hexanoate | C14H20O4 | 详情 | 详情 | |
(XXIII) | 11463 | 3-Bromo-1-propene; 3-Bromopropene;allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
(XXIV) | 11464 | methyl (2S)-2-[(1S)-1-hydroxy-4-(4-methoxyphenyl)butyl]-4-pentenoate | C17H24O4 | 详情 | 详情 | |
(XXV) | 11465 | (2R,3S)-2-Allyl-5-[(4-methoxybenzyl)oxy]-1,3-pentanediol | C16H24O4 | 详情 | 详情 | |
(XXVI) | 11466 | (2R)-2-[(2S,4S)-2-(4-Methoxyphenyl)-1,3-dioxan-4-yl]-4-penten-1-ol | C16H22O4 | 详情 | 详情 | |
(XXVII) | 11467 | (3S)-3-[(3S,5S)-5-(Iodomethyl)tetrahydro-3-furanyl]-4-(4-methoxyphenyl)-1-butanol | C16H23IO3 | 详情 | 详情 | |
(XXVIII) | 11468 | (3S)-3-[(3S,5S)-5-(Iodomethyl)tetrahydro-3-furanyl]-4-(4-methoxyphenyl)butanal | C16H21IO3 | 详情 | 详情 | |
(XXIX) | 11469 | (E)-2-Butenyl(triphenyl)stannane | C22H22Sn | 详情 | 详情 | |
(XXX) | 11470 | (3S,4S,6S)-6-[(3S,5S)-5-(Iodomethyl)tetrahydro-3-furanyl]-7-(4-methoxyphenyl)-3-methyl-1-hepten-4-ol | C20H29IO3 | 详情 | 详情 | |
(XXXI) | 11481 | ([(1S,2S)-1-[(2S)-2-[(3S,5S)-5-(Iodomethyl)tetrahydro-3-furanyl]-3-(4-methoxyphenyl)propyl]-2-methyl-3-butenyl]oxy)(triisopropyl)silane; (1S,2S)-1-[(2S)-2-[(3S,5S)-5-(Iodomethyl)tetrahydro-3-furanyl]-3-(4-methoxyphenyl)propyl]-2-methyl-3-butenyl triisopropylsilyl ether | C29H49IO3Si | 详情 | 详情 | |
(XXXIII) | 11471 | 1,4-Pentadien-3-ol | 922-65-6 | C5H8O | 详情 | 详情 |
(XXXIV) | 11472 | (1S)-1-[(2R)Oxiranyl]-2-propen-1-ol | C5H8O2 | 详情 | 详情 | |
(XXXV) | 11473 | (2S)-2-[(1S)-1-(4-Methoxybenzyl)-2-propenyl]oxirane; Methyl 4-[(2S)-2-[(2S)oxiranyl]-3-butenyl]phenyl ether | C13H16O2 | 详情 | 详情 | |
(XXXVI) | 11474 | (3S,4R)-7-Ethoxy-4-methoxy-3-(4-methoxybenzyl)-1-hepten-6-yne; 4-[(2S,3R)-6-Ethoxy-3-methoxy-2-vinyl-5-hexynyl]phenyl methyl ether | C18H24O3 | 详情 | 详情 | |
(XXXVII) | 11475 | ethyl (4R,5S)-5-hydroxy-4-methoxy-6-heptenoate | C10H18O4 | 详情 | 详情 | |
(XXXVIII) | 11476 | (5R,6S)-5-Methoxy-6-vinyltetrahydro-2H-pyran-2-one | C8H12O3 | 详情 | 详情 | |
(XXXIX) | 11585 | methyl (1R,5R)-5-methoxy-3-cyclohexene-1-carboxylate | C9H14O3 | 详情 | 详情 | |
(XL) | 11586 | methyl (1R,3R,4R)-4-hydroxy-3-methoxycyclohexanecarboxylate | C9H16O4 | 详情 | 详情 | |
(XLI) | 11588 | methyl (1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexanecarboxylate | C18H36O4Si | 详情 | 详情 | |
(XLII) | 11480 | [(1R,3R,4R)-3-Methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]methanol | C17H36O3Si | 详情 | 详情 | |
(XLIII) | 11532 | (1R,3R,4R)-3-Methoxy-4-[(triisopropylsilyl)oxy]cyclohexanecarbaldehyde | C17H34O3Si | 详情 | 详情 |