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【结 构 式】 
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【分子编号】35708 【品名】 【CA登记号】 |
【 分 子 式 】C36H54O8Si 【 分 子 量 】642.90546 【元素组成】C 67.26% H 8.47% O 19.91% Si 4.37% |
合成路线1
该中间体在本合成路线中的序号：(XXXVI)The cleavage of the 4-methoxybenzyl group of (XXXIII) with DDQ in dichloromethane/water gives the secondary alcohol (XXXIV), which is oxidized with pyridinium dichromate (PDC) in dichloromethane yielding the corresponding ketone (XXXV). The cyclization of (XXXV) with AcOH affords the tetracyclic compound (XXXVI), which is silylated at the carbinol group with Tes-OTf and lutidine giving the silyl ether (XXXVII). The oxidation of (XXXVII) with DMP in refluxing benzene affords the carbinol (XXXVIII), which is selectively desilylated and cyclized with TFA in dichloromethane/water giving the pentacyclic compound (XXXIX). The oxidation of the hydroxymethyl group of (XXXIX) with DMP in dichloromethane yields corresponding aldehyde (XL), which is silylated at the remaining OH group with Tbdms-OTf and lutidine in dichloromethane to afford the silyl ether (XLI). The oxidation of the aldehyde group of (XLI) with NaClO2 in tert-butanol/water gives the carboxylic acid (XLII).
| 【1】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-225,917 and CP-263,114 - Part 2: Evolution of the final strategy. Angew Chem. Int Ed Engl 1999, 38, 11, 1677. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXIII) | 35705 | C47H68O8Si | 详情 | 详情 | ||
| (XXXIV) | 35706 | C39H60O8Si | 详情 | 详情 | ||
| (XXXV) | 35707 | C39H58O8Si | 详情 | 详情 | ||
| (XXXVI) | 35708 | C36H54O8Si | 详情 | 详情 | ||
| (XXXVII) | 35709 | C42H68O8Si2 | 详情 | 详情 | ||
| (XXXVIII) | 35710 | C42H68O9Si2 | 详情 | 详情 | ||
| (XXXIX) | 35711 | C30H38O8 | 详情 | 详情 | ||
| (XL) | 35712 | C30H36O8 | 详情 | 详情 | ||
| (XLI) | 35713 | C36H50O8Si | 详情 | 详情 | ||
| (XLII) | 35714 | C36H50O9Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXXVI)The cleavage of the 4-methoxybenzyl group of (XXXIII) with DDQ in dichloromethane/water gives the secondary alcohol (XXXIV), which is oxidized with pyridinium dichromate (PDC) in dichloromethane yielding the corresponding ketone (XXXV). The cyclization of (XXXV) with AcOH affords the tetracyclic compound (XXXVI), which is silylated at the carbinol group with Tes-OTf and lutidine giving the silyl ether (XXXVII). The oxidation of (XXXVII) with DMP in refluxing benzene affords the carbinol (XXXVIII) (1), which is selectively desilylated and cyclized with TFA in dichloromethane/water giving the pentacyclic compound (XXXIX). The oxidation of the hydroxymethyl group of (XXXIX) with DMP in dichloromethane yields corresponding aldehyde (XL), which is silylated at the remaining OH group with Tbdms-OTf and lutidine in dichloromethane to afford the silyl ether (XLI). The oxidation of the aldehyde group of (XLI) with NaClO2 in tert-butanol/water gives the carboxylic acid (XLII).
| 【1】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-225,917 and CP-263,114 - Part 2: Evolution of the final strategy. Angew Chem. Int Ed Engl 1999, 38, 11, 1677. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXIII) | 35705 | C47H68O8Si | 详情 | 详情 | ||
| (XXXIV) | 35706 | C39H60O8Si | 详情 | 详情 | ||
| (XXXV) | 35707 | C39H58O8Si | 详情 | 详情 | ||
| (XXXVI) | 35708 | C36H54O8Si | 详情 | 详情 | ||
| (XXXVII) | 35709 | C42H68O8Si2 | 详情 | 详情 | ||
| (XXXVIII) | 35710 | C42H68O9Si2 | 详情 | 详情 | ||
| (XXXIX) | 35711 | C30H38O8 | 详情 | 详情 | ||
| (XL) | 35712 | C30H36O8 | 详情 | 详情 | ||
| (XLI) | 35713 | C36H50O8Si | 详情 | 详情 | ||
| (XLII) | 35714 | C36H50O9Si | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(IX)In an alternative procedure, nitrile (IX) was obtained by Horner-Emmons reaction of 3,3'-difluorobenzophenone (VIII) with diethyl (cyanomethyl)phosphonate. Catalytic hydrogenation of the olefinic double bond of (IX) provided the diaryl propionitrile (X), which was reduced to aldehyde (XI) using DIBAL. The chiral auxiliary (R)-1-amino-2-(methoxymethyl)pyrrolidine (XII) was then condensed with aldehyde (XI) to form hydrazone (XIII). Diastereoselective addition of methyllithium to the imino group yielded (XIV). Then, reductive cleavage of the resulting hydrazine (XIV) produced the title amine, which was converted to the corresponding hydrochloride.
| 【1】 Moe, S.T.; DelMar, E.G.; Smith, D.L.; et al.; Chiral synthesis and pharmacological evaluation of NPS 1407: A potent, stereoselective NMDA receptor antagonist. Bioorg Med Chem Lett 2000, 10, 21, 2411. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 35707 | C39H58O8Si | 详情 | 详情 | ||
| (IX) | 35708 | C36H54O8Si | 详情 | 详情 | ||
| (X) | 35709 | C42H68O8Si2 | 详情 | 详情 | ||
| (XI) | 46912 | 3,3-bis(3-fluorophenyl)propanal | C15H12F2O | 详情 | 详情 | |
| (XII) | 46913 | (2R)-2-(methoxymethyl)pyrrolidinylamine; (2R)-2-(methoxymethyl)-1-pyrrolidinamine | 59983-39-0 | C6H14N2O | 详情 | 详情 |
| (XIII) | 46914 | (2R)-N-[(E)-3,3-bis(3-fluorophenyl)propylidene]-2-(methoxymethyl)-1-pyrrolidinamine; N-[(E)-3,3-bis(3-fluorophenyl)propylidene]-N-[(2R)-2-(methoxymethyl)pyrrolidinyl]amine | C21H24F2N2O | 详情 | 详情 | |
| (XIV) | 46915 | (2R)-N-[(1S)-3,3-bis(3-fluorophenyl)-1-methylpropyl]-2-(methoxymethyl)-1-pyrrolidinamine; N-[(1S)-3,3-bis(3-fluorophenyl)-1-methylpropyl]-N-[(2R)-2-(methoxymethyl)pyrrolidinyl]amine | C22H28F2N2O | 详情 | 详情 |