|
【结 构 式】 
|
【分子编号】62941 【品名】2-[1,1'-biphenyl]-4-ylethyl 4-((2R,6R)-6-{(2S)-2-methyl-4-[(trimethylsilyl)methyl]-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)-2-butynyl ether; 4-(2-{[4-((2R,6R)-6-{(2S)-2-methyl-4-[(trimethylsilyl)methyl]-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)-2-butynyl]oxy}ethyl)-1,1'-biphenyl 【CA登记号】 |
【 分 子 式 】C33H44O2Si 【 分 子 量 】500.79666 【元素组成】C 79.15% H 8.86% O 6.39% Si 5.61% |
合成路线1
该中间体在本合成路线中的序号：(VIII)Synthesis of the acetylenic dihydropyran intermediate (VII): The reaction of the chiral oxazolinone (I) with allylmagnesium bromide (II) by means of CuBr, BF3/Et2O and Mg(OMe)2, followed by ozonolysis with O3 in dichloromethane gives the aldehyde (III), which is condensed with the enol ether (IV) by means of a chiral Cr catalist to yield the dihydropyranone(V). The reduction of (V) with NaBH4 and CeCl3, followed by acylation with Ac2O affords the acetoxydihydropyran derivative (VI). Which is finally condensed with the allenic tributyl tin compound (VII) and trimethylsilylmethyl magnesium chloride in THF to provide the target acetylenic dihydropyran intermediate (VIII).
| 【1】 Williams, D.R.; et al.; Synthesis of (-)-laulimalide: An agent for microtubule stabilization. Tetrahedron Lett 2002, 43, 27, 4841. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 62935 | (4R)-3-[(E)-2-butenoyl]-4-phenyl-1,3-oxazolidin-2-one | C13H13NO3 | 详情 | 详情 | |
| (II) | 10386 | Allyl(bromo)magnesium | 1730-25-2 | C3H5BrMg | 详情 | 详情 |
| (III) | 62936 | Methyl (3R)-3-methyl-5-oxopentanoate | C7H12O3 | 详情 | 详情 | |
| (IV) | 62937 | {[(E)-3-methoxy-1-methylene-2-propenyl]oxy}(trimethyl)silane; (E)-3-methoxy-1-methylene-2-propenyl trimethylsilyl ether | C8H16O2Si | 详情 | 详情 | |
| (V) | 62938 | methyl (3R)-3-methyl-4-[(2R)-4-oxo-3,4-dihydro-2H-pyran-2-yl]butanoate | C11H16O4 | 详情 | 详情 | |
| (VI) | 62939 | methyl (3R)-4-[(2R,4S)-4-(acetyloxy)-3,4-dihydro-2H-pyran-2-yl]-3-methylbutanoate | C13H20O5 | 详情 | 详情 | |
| (VII) | 62940 | 2-[1,1'-biphenyl]-4-ylethyl 2-(tributylstannyl)-2,3-butadienyl ether; 4-(2-{[2-(tributylstannyl)-2,3-butadienyl]oxy}ethyl)-1,1'-biphenyl | C30H44OSn | 详情 | 详情 | |
| (VIII) | 62941 | 2-[1,1'-biphenyl]-4-ylethyl 4-((2R,6R)-6-{(2S)-2-methyl-4-[(trimethylsilyl)methyl]-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)-2-butynyl ether; 4-(2-{[4-((2R,6R)-6-{(2S)-2-methyl-4-[(trimethylsilyl)methyl]-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)-2-butynyl]oxy}ethyl)-1,1'-biphenyl | C33H44O2Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VIII)Synthesis of the target Laulimalide: The condensation of the acetylenic dihydropyran intermediate (VIII) with the aldehydic epoxide intermediate (XIV) by means of BF3/Et2O, followed by silylation with TBDMS-OTf and DIEA gives the epoxide adduct (XV). The selective deprotection of (XV) with DDQ followed by oxidation with MnO2 and NaClO2 to yields the hydroxyacid (XVI), which is submitted to a macrocyclization by means of 2,4,6-trichlorobenzoyl chloride and DMAP to afford the acetylenic macrolactone (XVII). The selective monoreduction ossf the triple bond of (XVII) by means of H2 over Lindlar catalyst in the presence of 1- hexane and quinoline provides the silylated precursor (XVIII), which is finally deprotected by means od TBAF as usual to furnish the target Laulimalide.
| 【1】 Williams, D.R.; et al.; Synthesis of (-)-laulimalide: An agent for microtubule stabilization. Tetrahedron Lett 2002, 43, 27, 4841. |
| 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) | 62941 | 2-[1,1'-biphenyl]-4-ylethyl 4-((2R,6R)-6-{(2S)-2-methyl-4-[(trimethylsilyl)methyl]-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)-2-butynyl ether; 4-(2-{[4-((2R,6R)-6-{(2S)-2-methyl-4-[(trimethylsilyl)methyl]-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)-2-butynyl]oxy}ethyl)-1,1'-biphenyl | C33H44O2Si | 详情 | 详情 | |
| (XIV) | 62947 | (2S)-3-{(2S,3S,4E)-2-(2-[1,1'-biphenyl]-4-ylethoxy)-3-{[tert-butyl(dimethyl)silyl]oxy}-5-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-4-pentenyl}-2-oxiranecarbaldehyde | C34H46O5Si | 详情 | 详情 | |
| (XVI) | 62948 | 4-((2R,6R)-6-{(2S)-4-[(2S)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-((2R,3S)-3-{(2S,3S,4E)-3-{[tert-butyl(dimethyl)silyl]oxy}-2-hydroxy-5-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-4-pentenyl}oxiranyl)ethyl]-2-methyl-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl | C42H70O8Si2 | 详情 | 详情 | |
| (XVII) | 62949 | 7-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-12-[1-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-3-(4-methyl-3,6-dihydro-2H-pyran-2-yl)-2-propenyl]-3-methyl-5-methylidene-9,13,22-trioxatricyclo[16.3.1.0~8,10~]docos-19-en-15-yn-14-one | C42H68O7Si2 | 详情 | 详情 | |
| (XVIII) | 62950 | 7-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-12-[1-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-3-(4-methyl-3,6-dihydro-2H-pyran-2-yl)-2-propenyl]-3-methyl-5-methylidene-9,13,22-trioxatricyclo[16.3.1.0~8,10~]docosa-15,19-dien-14-one | C42H70O7Si2 | 详情 | 详情 |