|
【结 构 式】 
|
【分子编号】64658 【品名】 【CA登记号】 |
【 分 子 式 】C110H208O21Si8 【 分 子 量 】2091.53292 【元素组成】C 63.17% H 10.02% O 16.06% Si 10.74% |
合成路线1
该中间体在本合成路线中的序号：(LXXI)The cleavage of the Bom and benzyl protecting groups of (LXIX) by means of 1-methyl-1,4-cyclohexadiene and Pd(OH)2/C in ethanol, followed by oxidation with DMP gives the ketonic carbaldehyde compound (LXX) (4), which is condensed with the advanced intermediate phosphonium salt (XLI) by means of NaHMDS in toluene to yield the adduct (LXXI). The selective deprotection of the Tms silyl ester groups of (LXXI) with KF in methanol affords the dihydroxyacid (LXXII), which is submitted to macrolactonization by means of 2,4,6-trichlorobenzoyl chloride, DIEA and DMAP in toluene to provide the macrolactone (LXXIII). The fully desilylation of (LXXIII) by means of HF in acetonitrile/water gives rise to a 1:3 mixture of spongistatin 2 and its epimer (LXXIV) with the unnatural configuration being predominant. Perchloric acid mediated epimerization of (LXXIV) in the presence of calcium perchlorate leads to a 3.9-2.3:1 mixture (with the natural configuration being predominant), along with some degradation products (2).
| 【2】 Smith, A.B. III; Lin, Q.; Doughty, V.A.; Zhuang, L.; McBriar, M.D.; Kerns, J.K.; Brook, C.S.; Murase, N.; Nakayama, K.; The spongistatins: Architecturally complex natural products - Part two: Synthesis of the C(29-51) subunit, fragment assembly, and final elaboration to (+)-spongistatin 2. Angew Chem. Int Ed 2001, 40, 1, 196. |
| 【1】 Smith, A.B.; et al.; The spongistatins: Architecturally complex natural products - Part one: A formal synthesis of (+)-spongistatin 1 by construction of an advanced ABCD fragment. Angew Chem. Int Ed 2001, 40, 1, 191. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XLI) | 64629 | [4-((2R,3S,4S,6R)-4-{[tert-butyl(dimethyl)silyl]oxy}-6-{(S)-{(2R,3S,4R,5R,6R)-6-((4S,5E)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-methylene-5,7-octadienyl)-3-methyl-4,5-bis[(trimethylsilyl)oxy]tetrahydro-2H-pyran-2-yl}[(triethylsilyl)oxy]methyl}-6-methoxy-3-methyltetrahydro-2H-pyran-2-yl)butyl](triphenyl)phosphonium iodide | C69H118IO8PSi5 | 详情 | 详情 | |
| (LXIX) | 64656 | triisopropylsilyl 2-{(2S,4S,6R,8S,10S)-10-(acetyloxy)-2-{2-[(1R,2S,3R,4R)-2-(acetyloxy)-4-[(benzyloxy)methoxy]-5-((2S,4S,8R,10S)-8-[(benzyloxy)methyl]-10-{[tert-butyl(dimethyl)silyl]oxy}-4-methoxy-1,7-dioxaspiro[5.5]undec-2-yl)-1,3-dimethylpentyl]-2-propenyl}-4-methyl-4-[(triethylsilyl)oxy]-1-oxaspiro[5.5]undec-8-yl}acetate | C74H124O15Si3 | 详情 | 详情 | |
| (LXX) | 64657 | triisopropylsilyl 2-{(2S,4S,6R,8S,10S)-10-(acetyloxy)-2-{2-[(1R,2S,3S)-2-(acetyloxy)-5-((2S,4S,6R,8R,10S)-10-{[tert-butyl(dimethyl)silyl]oxy}-8-formyl-4-methoxy-1,7-dioxaspiro[5.5]undec-2-yl)-1,3-dimethyl-4-oxopentyl]-2-propenyl}-4-methyl-4-[(triethylsilyl)oxy]-1-oxaspiro[5.5]undec-8-yl}acetate | C59H106O14Si3 | 详情 | 详情 | |
| (LXXI) | 64658 | C110H208O21Si8 | 详情 | 详情 | ||
| (LXXII) | 64659 | C95H172O21Si5 | 详情 | 详情 | ||
| (LXXIII) | 64660 | (1R,3S,5S,6R,9R,10R,11R,13R,14S,15R,17S,18S,19R,25R,27S,29S,31S,33S,36S,37S,38R,41S,43S,49S)-3,37-bis(acetyloxy)-17,27-bis{[tert-butyl(dimethyl)silyl]oxy}-11-((4S,5E)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-methylene-5,7-octadienyl)-10-hydroxy-15,31-dimethoxy-18,36,38,43,49-pentamethyl-39-methylene-7,35-dioxo-14,43-bis[(triethylsilyl)oxy]-8,12,45,46,47,48-hexaoxaheptacyclo[39.3.1.1~1,5~.1~9,13~.1~15,19~.1~25,29~.1~29,33~] | C96H170O22Si5 | 详情 | 详情 | |
| (LXXIV) | 64661 | (1R,3S,5S,6R,9R,10R,11R,13R,14S,15R,17S,18R,19R,25R,27S,29S,31S,33S,36S,37S,38R,41S,43S,49S)-3,37-bis(acetyloxy)-10,14,17,27,43-pentahydroxy-11-[(4S,5E)-4-hydroxy-2-methylene-5,7-octadienyl]-15,31-dimethoxy-18,36,38,43,49-pentamethyl-39-methylene-7,35-dioxo-8,12,45,46,47,48-hexaoxaheptacyclo[39.3.1.1~1,5~.1~9,13~.1~15,19~.1~25,29~.1~29,33~] | C66H100O22 | 详情 | 详情 |