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【结 构 式】 
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【分子编号】57322 【品名】(2R)-2-[(2R,3R,5S,6R)-6-((1S,3S,5E)-6-{(4S,6R,11R)-4-[(1R,2S,3E)-2-({[(2S)-1-(tert-butoxycarbonyl)piperidinyl]carbonyl}oxy)-4-((1R,3R,4R)-4-{[tert-butyl(diphenyl)silyl]oxy}-3-methoxycyclohexyl)-1,3-dimethyl-3-butenyl]-2,2-dimethyl-9-oxo-1,3,7-trioxaspiro[5.5]undec-11-yl}-1-methoxy-3,5-dimethyl-5-hexenyl)-5-methoxy-3-methyltetrahydro-2H-pyran-2-yl]-2-hydroxyethanoic acid 【CA登记号】 |
【 分 子 式 】C68H103NO16Si 【 分 子 量 】1218.64846 【元素组成】C 67.02% H 8.52% N 1.15% O 21.01% Si 2.3% |
合成路线1
该中间体在本合成路线中的序号：(XXVII)The selective desilylation of (XXV) by means of TBAF gives the diol (XXVI), which is oxidized by means of NaClO and NaClO2 to yield the hydroxyacid (XXVII), which is methylated with diazomethane to afford the methyl ester (XXVIII). The cyclization of (XXVIII) by means of LiOH and Tes-OTf provides the macrocyclic alpha-hydroxy ketonic intermediate (XXIX), which is oxidized with DMP to the alpha diketonic intermediate (XXX).
| 【1】 Gleason, J.L.; The total synthesis of FK-506 and its spiroketal analogs. Diss Abstr Int B - Sci Eng 1994, 54, 12, Part 1, 6206. |
| 【2】 Ireland, R.E.; et al.; A total synthesis of FK-506. J Org Chem 1996, 61, 20, 6856. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXV) | 57320 | 2-[(1S,2E)-1-[(1R)-1-((4S,6R,11R)-11-{(E,4S,6S)-6-[(2R,3S,5R,6R)-6-((1S)-1,2-bis{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3-methoxy-5-methyltetrahydro-2H-pyran-2-yl]-6-methoxy-2,4-dimethyl-1-hexenyl}-2,2-dimethyl-9-oxo-1,3,7-trioxaspiro[5.5]undec-4-yl)ethyl]-3-((1R,3R,4R)-4-{[tert-butyl(diphenyl)silyl]oxy}-3-methoxycyclohexyl)-2-methyl-2-propenyl] 1-(tert-butyl) (2S)-1,2-piperidinedicarboxylate | C80H133NO15Si3 | 详情 | 详情 | |
| (XXVI) | 57321 | 1-(tert-butyl) 2-((1S,2E)-3-((1R,3R,4R)-4-{[tert-butyl(diphenyl)silyl]oxy}-3-methoxycyclohexyl)-1-{(1R)-1-[(4S,6R,11R)-11-((E,4S,6S)-6-{(2R,3S,5R,6R)-6-[(1S)-1,2-dihydroxyethyl]-3-methoxy-5-methyltetrahydro-2H-pyran-2-yl}-6-methoxy-2,4-dimethyl-1-hexenyl)-2,2-dimethyl-9-oxo-1,3,7-trioxaspiro[5.5]undec-4-yl]ethyl}-2-methyl-2-propenyl) (2S)-1,2-piperidinedicarboxylate | C68H105NO15Si | 详情 | 详情 | |
| (XXVII) | 57322 | (2R)-2-[(2R,3R,5S,6R)-6-((1S,3S,5E)-6-{(4S,6R,11R)-4-[(1R,2S,3E)-2-({[(2S)-1-(tert-butoxycarbonyl)piperidinyl]carbonyl}oxy)-4-((1R,3R,4R)-4-{[tert-butyl(diphenyl)silyl]oxy}-3-methoxycyclohexyl)-1,3-dimethyl-3-butenyl]-2,2-dimethyl-9-oxo-1,3,7-trioxaspiro[5.5]undec-11-yl}-1-methoxy-3,5-dimethyl-5-hexenyl)-5-methoxy-3-methyltetrahydro-2H-pyran-2-yl]-2-hydroxyethanoic acid | C68H103NO16Si | 详情 | 详情 | |
| (XXVIII) | 57323 | 1-(tert-butyl) 2-((1S,2E)-3-((1R,3R,4R)-4-{[tert-butyl(diphenyl)silyl]oxy}-3-methoxycyclohexyl)-1-{(1R)-1-[(4S,6R,11R)-11-((E,4S,6S)-6-{(2R,3S,5R,6R)-6-[(1R)-1-hydroxy-2-methoxy-2-oxoethyl]-3-methoxy-5-methyltetrahydro-2H-pyran-2-yl}-6-methoxy-2,4-dimethyl-1-hexenyl)-2,2-dimethyl-9-oxo-1,3,7-trioxaspiro[5.5]undec-4-yl]ethyl}-2-methyl-2-propenyl) (2S)-1,2-piperidinedicarboxylate | C69H105NO16Si | 详情 | 详情 | |
| (XXIX) | 57324 | (1R,6R,10S,12S,13R,14S,16R,17R,18R,25S,28S,29R,30R)-28-[(E)-2-((1R,3R,4R)-4-{[tert-butyl(diphenyl)silyl]oxy}-3-methoxycyclohexyl)-1-methylethenyl]-18-hydroxy-12,14-dimethoxy-8,10,16,29,32,32-hexamethyl-2,27,31,33,35-pentaoxa-20-azapentacyclo[28.3.1.1~13,17~.0~1,6~.0~20,25~]pentatriacont-7-ene-4,19,26-trione | C63H93NO13Si | 详情 | 详情 | |
| (XXX) | 57325 | (1R,6R,10S,12S,13R,14S,16R,17R,25S,28S,29R,30R)-28-[(E)-2-((1R,3R,4R)-4-{[tert-butyl(diphenyl)silyl]oxy}-3-methoxycyclohexyl)-1-methylethenyl]-12,14-dimethoxy-8,10,16,29,32,32-hexamethyl-2,27,31,33,35-pentaoxa-20-azapentacyclo[28.3.1.1~13,17~.0~1,6~.0~20,25~]pentatriacont-7-ene-4,18,19,26-tetrone | C63H91NO13Si | 详情 | 详情 |