【结 构 式】 |
【分子编号】33198 【品名】tert-butyl (2R,6S)-2-[(E)-2-[(1S,3S,3aR,4S,4aS,8aR,9aS)-1-methoxy-3-methyldodecahydronaphtho[2,3-c]furan-4-yl]ethenyl]-6-methyl-1-piperidinecarboxylate 【CA登记号】 |
【 分 子 式 】C27H45NO4 【 分 子 量 】447.65864 【元素组成】C 72.44% H 10.13% N 3.13% O 14.3% |
合成路线1
该中间体在本合成路线中的序号:(XVII)The reduction of piperidine-2(R)-carboxylic acid (XVII) with BH3/Me2S and BF3/Et2O in THF gives the carbinol (XVIII), which is treated with Boc2O and NaOH in THF yielding the carbamate (XIX). The silylation of the carbinol group of (XIX) with TBDMS-Cl and imidazole in DMF affords the silyl ether (XX), which is methylated with BuLi and methyl iodide providing the 2-methyl derivative (XXI). The desilylation of (XXI) with TBAF in THF affords the free carbinol (XXII), which is oxidized to the corresponding aldehyde (XXIII) with RuO4NPr4. The condensation of aldehyde (XXII) with the tricyclic sulfone intermediate (XVI) by means of BuLi in DME and sodium amalgam in methanol yields the vinylpiperidine intermediate (XVII), which is oxidized at the lactol group with Jones reagent (CrO3, H2SO4) giving the tricyclic lactone (XVIII). The deprotection of the piperidine ring of (XVIII) with TFA in dichloromethane yields the intermediate (XIX), which is finally methylated with formaldehyde and sodium cyanoborohydride in acetonitrile/water.
【1】 Wu, W.-L.; Hart, D.J.; Li, J.; Applications of Organosulfur Chemistry to Organic Synthesis: Total Synthesis of (+)-Himbeline and (-)-Himbacine. J Org Chem 1997, 62, 5023. |
【2】 Hart, D.J.and Wu, W.-L.; Total syntheses of (+)-Himbacine and (-)-Himbeline. J Am Chem Soc 1995, 117, 9369. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(XVI) | 33193 | [(1S,3S,3aS,4R,4aS,8aR,9aS)-1-methoxy-3-methyldodecahydronaphtho[2,3-c]furan-4-yl]methyl phenyl sulfone; (1S,3S,3aS,4R,4aS,8aR,9aS)-1-methoxy-3-methyl-4-[(phenylsulfonyl)methyl]dodecahydronaphtho[2,3-c]furan | C21H30O4S | 详情 | 详情 | |
(XVII) | 26751 | (2R)-2-piperidinecarboxylic acid | C6H11NO2 | 详情 | 详情 | |
(XVII) | 33198 | tert-butyl (2R,6S)-2-[(E)-2-[(1S,3S,3aR,4S,4aS,8aR,9aS)-1-methoxy-3-methyldodecahydronaphtho[2,3-c]furan-4-yl]ethenyl]-6-methyl-1-piperidinecarboxylate | C27H45NO4 | 详情 | 详情 | |
(XVIII) | 26746 | (2R)-piperidinylmethanol | C6H13NO | 详情 | 详情 | |
(XVIII) | 33199 | tert-butyl (2R,6S)-2-[(E)-2-[(3S,3aR,4S,4aS,8aR,9aS)-3-methyl-1-oxododecahydronaphtho[2,3-c]furan-4-yl]ethenyl]-6-methyl-1-piperidinecarboxylate | C26H41NO4 | 详情 | 详情 | |
(XIX) | 26747 | tert-butyl (2R)-2-(hydroxymethyl)-1-piperidinecarboxylate | C11H21NO3 | 详情 | 详情 | |
(XIX) | 33200 | (3S,3aR,4S,4aS,8aR,9aS)-3-methyl-4-[(E)-2-[(2R,6S)-6-methylpiperidinyl]ethenyl]decahydronaphtho[2,3-c]furan-1(3H)-one | C21H33NO2 | 详情 | 详情 | |
(XX) | 33194 | tert-butyl (2R)-2-([[tert-butyl(dimethyl)silyl]oxy]methyl)-1-piperidinecarboxylate | C17H35NO3Si | 详情 | 详情 | |
(XXI) | 33195 | tert-butyl (2R,6S)-2-([[tert-butyl(dimethyl)silyl]oxy]methyl)-6-methyl-1-piperidinecarboxylate | C18H37NO3Si | 详情 | 详情 | |
(XXII) | 33196 | tert-butyl (2R,6S)-2-(hydroxymethyl)-6-methyl-1-piperidinecarboxylate | C12H23NO3 | 详情 | 详情 | |
(XXIII) | 33197 | tert-butyl (2R,6S)-2-formyl-6-methyl-1-piperidinecarboxylate | C12H21NO3 | 详情 | 详情 |