【结 构 式】 |
【分子编号】11571 【品名】(4R,5S,6E)-5-[(4-methoxybenzyl)oxy]-7-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-4,6-dimethyl-6-hepten-2-ynyl pivalate 【CA登记号】 |
【 分 子 式 】C38H62O6Si 【 分 子 量 】642.99218 【元素组成】C 70.98% H 9.72% O 14.93% Si 4.37% |
合成路线1
该中间体在本合成路线中的序号:(IV)The synthesis of the C22-C34 subunit (C12-C16 of the chemical name) of FK-506 has been reported: The condensation of the chiral aldehyde (I) with the (S)-allenyl stannane (II) by means of boron trifluoride ethearate in dichloromethane yields an epimeric mixture of the acetylenic alcohol (III), which by protection with p-methoxybenzyl (PMB) trichloroacetimidate, followed by chromatographic separation, gives the enantiomerically pure protected acetylenic diol (IV). The reduction of (IV) with bis(2-methoxyethoxy)aluminum hydride in THF affords the (E,E)-dienic alcohol (V), which is submitted to a Sharpless asymmetric epoxidation with (-)-diethyl tartrate [(-)-DETR], titanium tetraisopropoxide and tert-butyl hydroperoxide (TBHP) in dichloromethane, yielding the chiral epoxy alcohol (VI). The reduction of (VI) with bis(2-methoxyethoxy)aluminum hydride in THF affords the partially protected triol (VII), which is finally dehydrogenated with dichlorodicyanobenzoquinone (DDQ) in dichloromethane to give the chiral 1,3-dioxane (VIII), which is the desired intermediate.
【1】 Marshall, J.A.; Xie, S.P.; Synthesis of a C22-34 subunit of the immunosuppressant FK-506. J Org Chem 1995, 60, 22, 7230. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
63307 | 1,1,1-trichloro-3-(4-methoxyphenyl)-2-propanimine | C10H10Cl3NO | 详情 | 详情 | ||
(I) | 11534 | (E)-3-[(1R,3R,4R)-3-Methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-2-methyl-2-propenal | C20H38O3Si | 详情 | 详情 | |
(II) | 11569 | 2-(tributylstannyl)-2,3-pentadienyl pivalate | C22H42O2Sn | 详情 | 详情 | |
(III) | 11570 | (4R,6E)-5-hydroxy-7-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-4,6-dimethyl-6-hepten-2-ynyl pivalate | C30H54O5Si | 详情 | 详情 | |
(IV) | 11571 | (4R,5S,6E)-5-[(4-methoxybenzyl)oxy]-7-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-4,6-dimethyl-6-hepten-2-ynyl pivalate | C38H62O6Si | 详情 | 详情 | |
(V) | 11572 | (2E,4R,5S,6E)-5-[(4-Methoxybenzyl)oxy]-7-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-4,6-dimethyl-2,6-heptadien-1-ol | C33H56O5Si | 详情 | 详情 | |
(VI) | 11573 | [(2R,3R)-3-((1S,2S,3E)-2-[(4-Methoxybenzyl)oxy]-4-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1,3-dimethyl-3-butenyl)oxiranyl]methanol | C33H56O6Si | 详情 | 详情 | |
(VII) | 11574 | (3S,4R,5S,6E)-5-[(4-Methoxybenzyl)oxy]-7-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-4,6-dimethyl-6-heptene-1,3-diol | C33H58O6Si | 详情 | 详情 | |
(VIII) | 11575 | 2-[(4S,5S,6S)-2-(4-Methoxyphenyl)-6-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-5-methyl-1,3-dioxan-4-yl]-1-ethanol | C33H56O6Si | 详情 | 详情 |