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【结 构 式】 
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【分子编号】57340 【品名】(2R,3S,5R,6S)-2-{(1S,3S,5E,7R)-7-[(4S)-2,2-diisopropyl-1,3-dioxolan-4-yl]-1-methoxy-3,5-dimethyl-5,9-decadienyl}-3,6-dimethoxy-5-methyltetrahydro-2H-pyran; (1S,3S,5E,7R)-7-[(4S)-2,2-diisopropyl-1,3-dioxolan-4-yl]-1-[(2R,3S,5R,6S)-3,6-dimethoxy-5-methyltetrahydro-2H-pyran-2-yl]-3,5-dimethyl-5,9-decadienyl methyl ether 【CA登记号】 |
【 分 子 式 】C30H54O6 【 分 子 量 】510.75516 【元素组成】C 70.55% H 10.66% O 18.79% |
合成路线1
该中间体在本合成路线中的序号：(XVII)Synthesis of the intermediate 14-iodo-10-tetradecenal dimethylacetal (XXI): The reaction of the chiral trihydroxy compound (XI) with 2,4-dimethyl-3-pentanone dimethyl acetal (XII) by means of TsOH in THF gives the ketal (XIII), which is treated with TsCl, TEA and DMAP in dichloromethane to yield the silyl ether (XIV). The condensation of (XIV) with ethynyl lithium (XV) in DMSO affords the propargyl derivative (XVI). The reduction of (XVI) with H2 over Lindlar catalyst in hexane containing quinoline provides the allyl derivative (XVII), which is condensed with propane-1,3-dithiol and BF3/Et2O in dichloromethane to give the chiral hydroxy dithiane (XVIII). The cleavage of the ketal group of (XVIII) by means of TsOH in methanol, followed by reaction of the intermediate diol with TsCl and pyridine yields the primary monotosylate (XIX), which is treated with Tbdms-OTf and lutidine in dichloromethane to afford the bis silyl ether (XX). Finally, this compound is iodinated by means of NaI, Cu and AgNO3 in hot acetonitrile/methanol to provide the desired intermediate 14-iodo-10-tetradecenal dimethylacetal (XXI).
| 【1】 Chen, K.; Formal total synthesis of (-)-FK506. Diss Abstr Int B - Sci Eng 1993, 53, 9, 4663. |
| 【2】 Smith, A.B. III; et al.; Formal total synthesis of FK506. Concise construction of the C(10)-C(34) segment via an effective coupling tactic. Tetrahedron Lett 1994, 35, 25, 4271. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 57298 | (2S,3S)-3-{(E,4S,6S)-6-[(2R,3S,5R,6S)-3,6-dimethoxy-5-methyltetrahydro-2H-pyran-2-yl]-6-methoxy-2,4-dimethyl-1-hexenyl}-1,2,4-butanetriol | C21H40O7 | 详情 | 详情 | |
| (XII) | 57336 | 3,3-dimethoxy-2,4-dimethylpentane; 1-isopropyl-1-methoxy-2-methylpropyl methyl ether | C9H20O2 | 详情 | 详情 | |
| (XIII) | 57337 | (2S,3E,6S,8S)-2-[(4S)-2,2-diisopropyl-1,3-dioxolan-4-yl]-8-[(2R,3S,5R,6S)-3,6-dimethoxy-5-methyltetrahydro-2H-pyran-2-yl]-8-methoxy-4,6-dimethyl-3-octen-1-ol | C28H52O7 | 详情 | 详情 | |
| (XIV) | 57338 | (2S,3E,6S,8S)-2-[(4S)-2,2-diisopropyl-1,3-dioxolan-4-yl]-8-[(2R,3S,5R,6S)-3,6-dimethoxy-5-methyltetrahydro-2H-pyran-2-yl]-8-methoxy-4,6-dimethyl-3-octenyl 4-methylbenzenesulfonate | C35H58O9S | 详情 | 详情 | |
| (XV) | 17461 | ethynyllithium | C2HLi | 详情 | 详情 | |
| (XVI) | 57339 | (2R,3S,5R,6S)-2-{(1S,3S,5E,7R)-7-[(4S)-2,2-diisopropyl-1,3-dioxolan-4-yl]-1-methoxy-3,5-dimethyl-5-decen-9-ynyl}-3,6-dimethoxy-5-methyltetrahydro-2H-pyran; (1S,3S,5E,7R)-7-[(4S)-2,2-diisopropyl-1,3-dioxolan-4-yl]-1-[(2R,3S,5R,6S)-3,6-dimethoxy-5-methyltetrahydro-2H-pyran-2-yl]-3,5-dimethyl-5-decen-9-ynyl methyl ether | C30H52O6 | 详情 | 详情 | |
| (XVII) | 57340 | (2R,3S,5R,6S)-2-{(1S,3S,5E,7R)-7-[(4S)-2,2-diisopropyl-1,3-dioxolan-4-yl]-1-methoxy-3,5-dimethyl-5,9-decadienyl}-3,6-dimethoxy-5-methyltetrahydro-2H-pyran; (1S,3S,5E,7R)-7-[(4S)-2,2-diisopropyl-1,3-dioxolan-4-yl]-1-[(2R,3S,5R,6S)-3,6-dimethoxy-5-methyltetrahydro-2H-pyran-2-yl]-3,5-dimethyl-5,9-decadienyl methyl ether | C30H54O6 | 详情 | 详情 | |
| (XVIII) | 57341 | (2R,4S,5R,6S,8S,10E,12R)-12-[(4S)-2,2-diisopropyl-1,3-dioxolan-4-yl]-2-(1,3-dithian-2-yl)-4,6-dimethoxy-8,10-dimethyl-10,14-pentadecadien-5-ol | C32H58O5S2 | 详情 | 详情 | |
| (XIX) | 57342 | (2S,3R,4E,7S,9S,10R,11S,13R)-3-allyl-13-(1,3-dithian-2-yl)-2,10-dihydroxy-9,11-dimethoxy-5,7-dimethyl-4-tetradecenyl 4-methylbenzenesulfonate | C32H52O7S3 | 详情 | 详情 | |
| (XX) | 57343 | (2S,3R,4E,7S,9S,10R,11S,13R)-3-allyl-2,10-bis{[tert-butyl(dimethyl)silyl]oxy}-13-(1,3-dithian-2-yl)-9,11-dimethoxy-5,7-dimethyl-4-tetradecenyl 4-methylbenzenesulfonate | C44H80O7S3Si2 | 详情 | 详情 | |
| (XXI) | 57344 | (1S,2R,3E,6S,8S,9R,10S,12R)-2-allyl-9-{[tert-butyl(dimethyl)silyl]oxy}-1-(iodomethyl)-8,10,13,13-tetramethoxy-4,6,12-trimethyl-3-tridecenyl tert-butyl(dimethyl)silyl ether; (5S,6R,7E,10S,12S,13R)-6-allyl-5-(iodomethyl)-12-methoxy-2,2,3,3,8,10,15,15,16,16-decamethyl-13-[(1S,3R)-1,4,4-trimethoxy-3-methylbutyl]-4,14-dioxa-3,15-disila-7-heptadecene | C36H73IO6Si2 | 详情 | 详情 |