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【结 构 式】 
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【分子编号】61307 【品名】4-({(1S,2E,5S,6S,7E)-1-(2-{(2S)-3-[(2R,6R)-6-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl}-2-propenyl)-5-{[tert-butyl(diphenyl)silyl]oxy}-6-(methoxymethoxy)-8-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-2,7-octadienyl}oxy)-2-pentanone 【CA登记号】 |
【 分 子 式 】C57H88O8Si2 【 分 子 量 】957.49192 【元素组成】C 71.5% H 9.26% O 13.37% Si 5.87% |
合成路线1
该中间体在本合成路线中的序号：(XXII)Synthesis of the target compound: The condensation of the 1,3-dioxane intermediate (XIII) with the target dihydropyran intermediate (XX) by means of TiCl4 and TEA in dichloromethane gives the adduct (XXI), whose OH group is oxidized by means of DMP to yield the ketone (XXII). Elimination of the chiral auxiliary of (XXII) by means of K2CO3 in methanol, followed by protection with Mom-Cl and DIEA in DMF affords the fully protected compound (XXIII). Both Tbdms and Tbdps protecting groups of (XXIII) were exchanged for Tes groups by cleavage with TBAF, followed by reaction with Tes-Cl and pyridine to provide compound (XXIV). Selective Swern oxidation of the primary silyl ether group of (XXIV) gives aldehyde (XXV), which is condensed with phosphonate (XXVI) by means of KHMDS in THF to yield the trimethylsilylethyl ester (XXVII). The desilylation of (XXVII) by means of TBAF in THF affords the hydroxyacid (XXVIII), which is submitted to a macrocyclization by means of 2,4,6-trichlorobenzoyl chloride to provide the macrolactone (XXIX). Finally, this compound is deprotected by a treatment with Me2BBr and submitted to a selective Sharpless epoxidation to afford the target Laulimalide
| 【1】 Mulzer, J.; Hanbauer, M.; Total synthesis of the antitumor agent (-)-laulimalide. Tetrahedron Lett 2002, 43, 18, 3381. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIII) | 61155 | tert-butyl(diphenyl)silyl (1S,2S,3E)-1-{(E)-3-[(4R,6R)-4,6-dimethyl-1,3-dioxan-2-yl]-2-propenyl}-2-(methoxymethoxy)-4-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-3-butenyl ether; (5S,6S)-6-{(E)-3-[(4R,6R)-4,6-dimethyl-1,3-dioxan-2-yl]-2-propenyl}-9,9-dimethyl-5-{(E)-2-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]ethenyl}-8,8-diphenyl-2,4,7-trioxa-8-siladecane | C37H52O6Si | 详情 | 详情 | |
| (XX) | 61305 | tert-butyl(dimethyl)[2-((2R,6R)-6-{(2S)-2-methyl-4-[(trimethylsilyl)methyl]-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)ethoxy]silane; tert-butyl(dimethyl)silyl 2-((2R,6R)-6-{(2S)-2-methyl-4-[(trimethylsilyl)methyl]-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)ethyl ether | C23H46O2Si2 | 详情 | 详情 | |
| (XXI) | 61306 | 4-({(1S,2E,5S,6S,7E)-1-(2-{(2S)-3-[(2R,6R)-6-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl}-2-propenyl)-5-{[tert-butyl(diphenyl)silyl]oxy}-6-(methoxymethoxy)-8-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-2,7-octadienyl}oxy)-2-pentanol | C57H90O8Si2 | 详情 | 详情 | |
| (XXII) | 61307 | 4-({(1S,2E,5S,6S,7E)-1-(2-{(2S)-3-[(2R,6R)-6-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl}-2-propenyl)-5-{[tert-butyl(diphenyl)silyl]oxy}-6-(methoxymethoxy)-8-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-2,7-octadienyl}oxy)-2-pentanone | C57H88O8Si2 | 详情 | 详情 | |
| (XXIII) | 61308 | tert-butyl(dimethyl)silyl 2-((2R,6R)-6-{(2S,6S,7E,10S,11S,12E)-10-{[tert-butyl(diphenyl)silyl]oxy}-6,11-bis(methoxymethoxy)-2-methyl-13-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-4-methylene-7,12-tridecadienyl}-5,6-dihydro-2H-pyran-2-yl)ethyl ether; (5S,6E,9S)-5-(2-{(2S)-3-[(2R,6R)-6-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl}-2-propenyl)-9-{(1S,2E)-1-(methoxymethoxy)-3-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-2-propenyl}-12,12-dimethyl-11,11-diphenyl-2,4,10-trioxa-11-sila-6-tridecene | C54H84O8Si2 | 详情 | 详情 | |
| (XXIV) | 61309 | (5S,6E,9S)-11,11-diethyl-9-{(1S,2E)-1-(methoxymethoxy)-3-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-2-propenyl}-5-{2-[(2S)-2-methyl-3-((2R,6R)-6-{2-[(triethylsilyl)oxy]ethyl}-3,6-dihydro-2H-pyran-2-yl)propyl]-2-propenyl}-2,4,10-trioxa-11-sila-6-tridecene; 2-((2R,6R)-6-{(2S,6S,7E,10S,11S,12E)-6,11-bis(methoxymethoxy)-2-methyl-13-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-4-methylene-10-[(triethylsilyl)oxy]-7,12-tridecadienyl}-5,6-dihydro-2H-pyran-2-yl)ethyl triethylsilyl ether | C44H80O8Si2 | 详情 | 详情 | |
| (XXV) | 61310 | 2-((2R,6R)-6-{(2S,6S,7E,10S,11S,12E)-6,11-bis(methoxymethoxy)-2-methyl-13-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-4-methylene-10-[(triethylsilyl)oxy]-7,12-tridecadienyl}-5,6-dihydro-2H-pyran-2-yl)acetaldehyde | C38H64O8Si | 详情 | 详情 | |
| (XXVI) | 61311 | 2-(trimethylsilyl)ethyl 2-(diphenoxyphosphoryl)acetate | C19H25O5PSi | 详情 | 详情 | |
| (XXVII) | 61312 | 2-(trimethylsilyl)ethyl (E)-4-((2R,6R)-6-{(2S,6S,7E,10S,11S,12E)-6,11-bis(methoxymethoxy)-2-methyl-13-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-4-methylene-10-[(triethylsilyl)oxy]-7,12-tridecadienyl}-5,6-dihydro-2H-pyran-2-yl)-2-butenoate | C45H78O9Si2 | 详情 | 详情 | |
| (XXVIII) | 61313 | (E)-4-((2R,6R)-6-{(2S,6S,7E,10S,11S,12E)-10-hydroxy-6,11-bis(methoxymethoxy)-2-methyl-13-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-4-methylene-7,12-tridecadienyl}-5,6-dihydro-2H-pyran-2-yl)-2-butenoic acid | C34H52O9 | 详情 | 详情 | |
| (XXIX) | 61314 | (1R,7S,11S,15S,17R)-11-(methoxymethoxy)-7-{(1S,2E)-1-(methoxymethoxy)-3-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-2-propenyl}-15-methyl-13-methylene-6,21-dioxabicyclo[15.3.1]henicosa-3,9,19-trien-5-one | C34H50O8 | 详情 | 详情 |