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【结 构 式】 
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【分子编号】35703 【品名】 【CA登记号】 |
【 分 子 式 】C49H74O9Si 【 分 子 量 】835.20666 【元素组成】C 70.47% H 8.93% O 17.24% Si 3.36% |
合成路线1
该中间体在本合成路线中的序号：(XXXI)The reduction of the ester group of (XXVI) with DIBAL in toluene gives the carbinol (XXVII), which is treated with tert-butyl hydroperoxide and Et2Al-CN in toluene to yield the dihydroxy-carbonitrile (XXVIII). The sulfonation of the primary OH group of (XXVIII) with Ms-Cl affords the mesylate (XXIX), which is treated with K2CO3 in methanol providing the intermediate epoxide (XXX). The reaction of (XXX) with oxalic acid in ethanol/water affords the maleic anhydride derivative (XXXI), which by a selective hydrolysis with aqueous AcOH gives the alpha hydroxy ketone (XXXII). The silylation of the OH group of (XXXII) with TBDMS-OTf and lutidine in dichloromethane yields the silyl ether (XXXIII).
| 【1】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-263,114 and CP-225,917 - Part 1: Synthesis of key intermediates and intelligence gathering. Angew Chem. Int Ed Engl 1999, 38, 11, 1669. |
合成路线2
该中间体在本合成路线中的序号：(XXXV)The reaction of (XXVIII) with Pd and CO in MeOH gives the methyl ester (XXIX), which is treated with PhI(OCOCF3)2 and MeOH to afford the gem-dimethoxy compound (XXX). The reduction of the ester group of (XXX) with DIBAL in toluene gives the carbinol (XXXI), which is treated with tert-butyl hydroperoxide and Et2Al-CN in toluene to yield the dihydroxycarbonitrile (XXXII). The sulfonation of the primary OH group of (XXXII) with MsCl affords the mesylate (XXXIII), which is treated with K2CO3 in MeOH providing the intermediate epoxide (XXXIV). The reaction of (XXXIV) with oxalic acid in EtOH/H2O affords the maleic anhydride derivative (XXXV).
| 【1】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-263,114 and CP-225,917 - Part 1: Synthesis of key intermediates and intelligence gathering. Angew Chem. Int Ed Engl 1999, 38, 11, 1669. |
| 【2】 Nicolaou, K.C.; et al.; The absolute configuration and asymmetric total synthesis of the CP molecules (CP-263,114 and CP-225,917, Phomoidrides B and A). Angew Chem. Int Ed Engl 2000, 39, 10, 1829. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 15713 | Oxalic acid | 144-62-7 | C2H2O4 | 详情 | 详情 | |
| (XXVIII) | 35696 | C49H75F3O7S3Si | 详情 | 详情 | ||
| (XXIX) | 35697 | C50H78O6S2Si | 详情 | 详情 | ||
| (XXX) | 35698 | C49H78O8Si | 详情 | 详情 | ||
| (XXXI) | 35699 | C48H78O7Si | 详情 | 详情 | ||
| (XXXII) | 35700 | C49H79NO8Si | 详情 | 详情 | ||
| (XXXIII) | 40299 | C51H83NO8SSi | 详情 | 详情 | ||
| (XXXIV) | 35702 | C49H77NO7Si | 详情 | 详情 | ||
| (XXXV) | 35703 | C49H74O9Si | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XXXV)The selective hydrolysis of (XXXV) with aqueous AcOH gives the alpha hydroxy ketone (XXXVI), which is silylated at the OH group with TBDMS-OTf and lutidine in dichloromethane yielding the silyl ether (XXXVII). The cleavage of the 4-methoxybenzyl group of (XXXVII) with DDQ in CH2Cl2/H2O gives the secondary alcohol (XXXVIII), which is oxidized with pyridinium dichromate (PDC) in dichloromethane yielding the corresponding ketone (XXXIX). The cyclization of (XXXIX) with AcOH affords the tetracyclic compound (XL), which is silylated at the carbinol group with TES-OTf and lutidine giving the silyl ether (XLI). The oxidation of (XLI) with DMP in refluxing benzene affords the carbinol (XLII), which is selectively desilylated and cyclized with TFA in CH2Cl2/H2O giving the pentacyclic compound (XLIII). The oxidation of the hydroxymethyl group of (XLIII) with DMP in CH2Cl2 yields corresponding aldehyde (XLIV).
| 【1】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-263,114 and CP-225,917 - Part 1: Synthesis of key intermediates and intelligence gathering. Angew Chem. Int Ed Engl 1999, 38, 11, 1669. |
| 【2】 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. |
| 【3】 Nicolaou, K.C.; et al.; The absolute configuration and asymmetric total synthesis of the CP molecules (CP-263,114 and CP-225,917, Phomoidrides B and A). Angew Chem. Int Ed Engl 2000, 39, 10, 1829. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXV) | 35703 | C49H74O9Si | 详情 | 详情 | ||
| (XXXVI) | 35704 | C41H54O8 | 详情 | 详情 | ||
| (XXXVII) | 35705 | C47H68O8Si | 详情 | 详情 | ||
| (XXXVIII) | 35706 | C39H60O8Si | 详情 | 详情 | ||
| (XXXIX) | 35707 | C39H58O8Si | 详情 | 详情 | ||
| (XL) | 40300 | (8S,14R,15R)-15-((2S,6E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-oxo-6-octenyl)-11-hydroxy-8-(hydroxymethyl)-14-[(E)-6-octenyl]-4,10-dioxatetracyclo[9.4.0.0(2,6).0(8,12)]pentadeca-2(6),12-diene-3,5-dione | C36H54O8Si | 详情 | 详情 | |
| (XLI) | 40301 | (8R,14R,15R)-15-((2S,6E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-oxo-6-octenyl)-11-hydroxy-14-[(E)-6-octenyl]-8-[[(triethylsilyl)oxy]methyl]-4,10-dioxatetracyclo[9.4.0.0(2,6).0(8,12)]pentadeca-2(6),12-diene-3,5-dione | C42H68O8Si2 | 详情 | 详情 | |
| (XLII) | 35710 | C42H68O9Si2 | 详情 | 详情 | ||
| (XLIII) | 35711 | C30H38O8 | 详情 | 详情 | ||
| (XLIV) | 35712 | C30H36O8 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(XXXI)The reduction of the ester group of (XXVI) with DIBAL in toluene gives the carbinol (XXVII), which is treated with tert-butyl hydroperoxide and Et2Al-CN in toluene to yield the dihydroxy-carbonitrile (XXVIII). The sulfonation of the primary OH group of (XXVIII) with Ms-Cl affords the mesylate (XXIX), which is treated with K2CO3 in methanol providing the intermediate epoxide (XXX). The reaction of (XXX) with oxalic acid in ethanol/water affords the maleic anhydride derivative (XXXI), which by a selective hydrolysis with aqueous AcOH gives the alpha hydroxy ketone (XXXII). The silylation of the OH group of (XXXII) with Tbdms-OTf and lutidine in dichloromethane yields the silyl ether (XXXIII).
| 【1】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-263,114 and CP-225,917 - Part 1: Synthesis of key intermediates and intelligence gathering. Angew Chem. Int Ed Engl 1999, 38, 11, 1669. |
合成路线5
该中间体在本合成路线中的序号：(XXXV)The reaction of (XXVIII) with Pd and CO in MeOH gives the methyl ester (XXIX), which is treated with PhI(OCOCF3)2 and MeOH to afford the gem-dimethoxy compound (XXX). The reduction of the ester group of (XXX) with DIBAL in toluene gives the carbinol (XXXI), which is treated with tert-butyl hydroperoxide and Et2Al(CN) in toluene to yield the dihydroxycarbonitrile (XXXII). The sulfonation of the primary OH group of (XXXII) with MsCl affords mesylate (XXXIII), which is treated with K2CO3 in MeOH providing intermediate epoxide (XXXIV). The reaction of (XXXIV) with oxalic acid affords the maleic anhydride derivative (XXXV).
| 【1】 Nicolaou, K.C.; et al.; The absolute configuration and asymmetric total synthesis of the CP molecules (CP-263,114 and CP-225,917, Phomoidrides B and A). Angew Chem. Int Ed Engl 2000, 39, 10, 1829. |
| 【2】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-263,114 and CP-225,917 - Part 1: Synthesis of key intermediates and intelligence gathering. Angew Chem. Int Ed Engl 1999, 38, 11, 1669. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 15713 | Oxalic acid | 144-62-7 | C2H2O4 | 详情 | 详情 | |
| (XXVIII) | 35696 | C49H75F3O7S3Si | 详情 | 详情 | ||
| (XXIX) | 35697 | C50H78O6S2Si | 详情 | 详情 | ||
| (XXX) | 35698 | C49H78O8Si | 详情 | 详情 | ||
| (XXXI) | 35699 | C48H78O7Si | 详情 | 详情 | ||
| (XXXII) | 35700 | C49H79NO8Si | 详情 | 详情 | ||
| (XXXIII) | 40299 | C51H83NO8SSi | 详情 | 详情 | ||
| (XXXIV) | 35702 | C49H77NO7Si | 详情 | 详情 | ||
| (XXXV) | 35703 | C49H74O9Si | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(XXXV)The selective hydrolysis of (XXXV) with aqueous AcOH gives the alpha hydroxy ketone (XXXVI), which is silylated at the OH group with TBDMS-OTf and lutidine in dichloromethane yielding the silyl ether (XXXVII). The cleavage of the 4-methoxybenzyl group of (XXXVII) with DDQ in dichloromethane/water gives the secondary alcohol (XXXVIII), which is oxidized with pyridinium dichromate (PDC) in dichloromethane yielding the corresponding ketone (XXXIX). The cyclization of (XXXIX) with AcOH affords the tetracyclic compound (XL), which is silylated at the carbinol group with TES-OTf and lutidine giving the silyl ether (XLI). The oxidation of (XLI) with DMP in refluxing benzene affords the carbinol (XLII), which is selectively desilylated and cyclized with TFA in dichloromethane/water giving the pentacyclic compound (XLIII). The oxidation of the hydroxymethyl group of (XLIII) with DMP in dichloromethane yields corresponding aldehyde (XLIV).
| 【1】 Nicolaou, K.C.; et al.; The absolute configuration and asymmetric total synthesis of the CP molecules (CP-263,114 and CP-225,917, Phomoidrides B and A). Angew Chem. Int Ed Engl 2000, 39, 10, 1829. |
| 【2】 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. |
| 【3】 Nicolaou, K.C.; et al.; Total synthesis of the CP molecules CP-263,114 and CP-225,917 - Part 1: Synthesis of key intermediates and intelligence gathering. Angew Chem. Int Ed Engl 1999, 38, 11, 1669. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXV) | 35703 | C49H74O9Si | 详情 | 详情 | ||
| (XXXVI) | 35704 | C41H54O8 | 详情 | 详情 | ||
| (XXXVII) | 35705 | C47H68O8Si | 详情 | 详情 | ||
| (XXXVIII) | 35706 | C39H60O8Si | 详情 | 详情 | ||
| (XXXIX) | 35707 | C39H58O8Si | 详情 | 详情 | ||
| (XL) | 40300 | (8S,14R,15R)-15-((2S,6E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-oxo-6-octenyl)-11-hydroxy-8-(hydroxymethyl)-14-[(E)-6-octenyl]-4,10-dioxatetracyclo[9.4.0.0(2,6).0(8,12)]pentadeca-2(6),12-diene-3,5-dione | C36H54O8Si | 详情 | 详情 | |
| (XLI) | 40301 | (8R,14R,15R)-15-((2S,6E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-oxo-6-octenyl)-11-hydroxy-14-[(E)-6-octenyl]-8-[[(triethylsilyl)oxy]methyl]-4,10-dioxatetracyclo[9.4.0.0(2,6).0(8,12)]pentadeca-2(6),12-diene-3,5-dione | C42H68O8Si2 | 详情 | 详情 | |
| (XLII) | 35710 | C42H68O9Si2 | 详情 | 详情 | ||
| (XLIII) | 35711 | C30H38O8 | 详情 | 详情 | ||
| (XLIV) | 35712 | C30H36O8 | 详情 | 详情 |