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【结 构 式】 
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【分子编号】35698 【品名】 【CA登记号】 |
【 分 子 式 】C49H78O8Si 【 分 子 量 】823.23902 【元素组成】C 71.49% H 9.55% O 15.55% Si 3.41% |
合成路线1
该中间体在本合成路线中的序号：(XXVI)The cyclization of (XVII) by means of Me2AlCl in dichloromethane gives the tricyclic ketone (XVIII), which is desilylated with TBAF in THF yielding the ethanol (XIX). The oxidation of (XIX) with Dess Martin periodinane (DMP) in dichloromethane affords the corresponding aldehyde (XX), which is condensed with the lithium 1,3-dithiane (XXI) in THF to give the secondary alcohol (XXII). The silylation of this alcohol with Tes-OTf and NaH in THF yields the silyl ether (XXIII), which is treated with Ph-NTf2 and KHMDS in THF to afford the enol ether (XXIV). The reaction of (XXIV) with Pdo and CO in methanol gives the methyl ester (XXV), which is treated with PhI(OCOCF3)2 and methanol to afford the gem-dimethoxy compound (XXVI).
| 【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. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVII) | 35689 | (E)-1-(5-[(2E,9E)-1-[(E)-2-(4-methoxyphenyl)ethylidene]-2,9-undecadienyl]-2,2-dimethyl-1,3-dioxan-5-yl)-7-[(triisopropylsilyl)oxy]-4-hepten-3-one | C42H68O5Si | 详情 | 详情 | |
| (XVIII) | 35690 | C42H68O5Si | 详情 | 详情 | ||
| (XIX) | 35691 | C33H48O5 | 详情 | 详情 | ||
| (XX) | 35692 | C33H46O5 | 详情 | 详情 | ||
| (XXI) | 35693 | [2-[(E)-3-pentenyl]-1,3-dithian-2-yl]lithium | C9H15LiS2 | 详情 | 详情 | |
| (XXII) | 35694 | C42H62O5S2 | 详情 | 详情 | ||
| (XXIII) | 35695 | C48H76O5S2Si | 详情 | 详情 | ||
| (XXIV) | 35696 | C49H75F3O7S3Si | 详情 | 详情 | ||
| (XXV) | 35697 | C50H78O6S2Si | 详情 | 详情 | ||
| (XXVI) | 35698 | C49H78O8Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXVI)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3
该中间体在本合成路线中的序号：(XXX)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4
该中间体在本合成路线中的序号：(XXVI)The cyclization of (XVII) by means of Me2AlCl in dichloromethane gives the tricyclic ketone (XVIII), which is desilylated with TBAF in THF yielding the ethanol (XIX). The oxidation of (XIX) with Dess Martin periodinane (DMP) in dichloromethane affords the corresponding aldehyde (XX), which is condensed with the lithium 1,3-dithiane (XXI) in THF to give the secondary alcohol (XXII). The silylation of this alcohol with Tes-OTf and NaH in THF yields the silyl ether (XXIII), which is treated with Ph-NTf2 and KHMDS in THF to afford the enol ether (XXIV). The reaction of (XXIV) with Pdo and CO in methanol gives the methyl ester (XXV), which is treated with PhI(OCOCF3)2 and methanol to afford the gem-dimethoxy compound (XXVI).
| 【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. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVII) | 35689 | (E)-1-(5-[(2E,9E)-1-[(E)-2-(4-methoxyphenyl)ethylidene]-2,9-undecadienyl]-2,2-dimethyl-1,3-dioxan-5-yl)-7-[(triisopropylsilyl)oxy]-4-hepten-3-one | C42H68O5Si | 详情 | 详情 | |
| (XVIII) | 35690 | C42H68O5Si | 详情 | 详情 | ||
| (XIX) | 35691 | C33H48O5 | 详情 | 详情 | ||
| (XX) | 35692 | C33H46O5 | 详情 | 详情 | ||
| (XXI) | 35693 | [2-[(E)-3-pentenyl]-1,3-dithian-2-yl]lithium | C9H15LiS2 | 详情 | 详情 | |
| (XXII) | 35694 | C42H62O5S2 | 详情 | 详情 | ||
| (XXIII) | 35695 | C48H76O5S2Si | 详情 | 详情 | ||
| (XXIV) | 35696 | C49H75F3O7S3Si | 详情 | 详情 | ||
| (XXV) | 35697 | C50H78O6S2Si | 详情 | 详情 | ||
| (XXVI) | 35698 | C49H78O8Si | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(XXVI)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6
该中间体在本合成路线中的序号：(XXX)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 |