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【结 构 式】 
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【分子编号】32440 【品名】(1E,3S,5E)-1,6-diiodo-2-methyl-1,5-hexadien-3-ol 【CA登记号】 |
【 分 子 式 】C7H10I2O 【 分 子 量 】363.96474 【元素组成】C 23.1% H 2.77% I 69.73% O 4.4% |
合成路线1
该中间体在本合成路线中的序号：(XXVIII)The reaction of 5-iodo-4-methyl-3-(tert-butydimethylsilyloxy)-4-pentenal (XXVI) with methyl iodide and CrCl2 in dioxane/THF gives the diiodohexenal (XXVII), which is desilylated with TBAF in THF yielding the secondary alcohol (XXVIII). The esterification of (XXVIII) with protected perhydropyridazinecarboxylic acid (XXIX) by means of EDC and DIEA in dichloromethane affords the carboxylic ester (XXX), which is deprotected with TFA in dichloromethane to give the unprotected ester (XXXI). The condensation of (XXXI) with carboxylic acid (XXXII) by means of 1-hydroxy-7-azabenzotriazole (HOAt) and EDC in dichloromethane yields the protected amide (XXXIII), which is deprotected with TFA affording (XXXIV) with a free amino group. The condensation of (XXXIV) with the acid (XXXV) (obtained by oxidation of carbinol (XXXVI) with tetrapropylammonium perruthenate (TPAP)) by means of O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU) and DIEA in DMF provides the amide (XXXVII), which is cyclized by means of triphenylarsine and Pd dibenzylideneacetone complex yielding the cyclic intermediate (XXXVIII).
| 【1】 Nicolaou, K.C.; et al.; Total synthesis of sanglifehrin A. Angew Chem. Int Ed Engl 1999, 38, 16, 2447. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXVI) | 32438 | (3S,4E)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-iodo-4-methyl-4-pentenal | C12H23IO2Si | 详情 | 详情 | |
| (XXVII) | 32439 | tert-butyl([(1S,3E)-4-iodo-1-[(E)-2-iodo-1-methylethenyl]-3-butenyl]oxy)dimethylsilane; tert-butyl(dimethyl)silyl (1S,3E)-4-iodo-1-[(E)-2-iodo-1-methylethenyl]-3-butenyl ether | C13H24I2OSi | 详情 | 详情 | |
| (XXVIII) | 32440 | (1E,3S,5E)-1,6-diiodo-2-methyl-1,5-hexadien-3-ol | C7H10I2O | 详情 | 详情 | |
| (XXIX) | 32441 | (3S)-1,2-bis(tert-butoxycarbonyl)hexahydro-3-pyridazinecarboxylic acid | C15H26N2O6 | 详情 | 详情 | |
| (XXX) | 32442 | 1,2-di(tert-butyl) 3-[(1S,3E)-4-iodo-1-[(E)-2-iodo-1-methylethenyl]-3-butenyl] (3S)tetrahydro-1,2,3-pyridazinetricarboxylate | C22H34I2N2O6 | 详情 | 详情 | |
| (XXXI) | 32443 | (1S,3E)-4-iodo-1-[(E)-2-iodo-1-methylethenyl]-3-butenyl (3S)hexahydro-3-pyridazinecarboxylate | C12H18I2N2O2 | 详情 | 详情 | |
| (XXXII) | 32444 | (2S)-2-([(2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutanoyl]amino)-3-(3-hydroxyphenyl)propionic acid | C19H28N2O6 | 详情 | 详情 | |
| (XXXIII) | 32445 | (1S,3E)-4-iodo-1-[(E)-2-iodo-1-methylethenyl]-3-butenyl (3S)-1-[(2S)-2-([(2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutanoyl]amino)-3-(3-hydroxyphenyl)propanoyl]hexahydro-3-pyridazinecarboxylate | C31H44I2N4O7 | 详情 | 详情 | |
| (XXXIV) | 32446 | (1S,3E)-4-iodo-1-[(E)-2-iodo-1-methylethenyl]-3-butenyl (3S)-1-[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-(3-hydroxyphenyl)propanoyl]hexahydro-3-pyridazinecarboxylate | C26H36I2N4O5 | 详情 | 详情 | |
| (XXXV) | 32447 | (3R,4S,5R,6R)-1,4-dimethyl-3-[(E)-2-(tributylstannyl)ethenyl]-2,9-dioxabicyclo[3.3.1]nonane-6-carboxylic acid | C24H44O4Sn | 详情 | 详情 | |
| (XXXVI) | 32448 | [(3R,4S,5S,6S)-1,4-dimethyl-3-[(E)-2-(tributylstannyl)ethenyl]-2,9-dioxabicyclo[3.3.1]non-6-yl]methanol | C24H46O3Sn | 详情 | 详情 | |
| (XXXVII) | 32449 | (1S,3E)-4-iodo-1-[(E)-2-iodo-1-methylethenyl]-3-butenyl (3S)-1-[(2S)-2-([(2S)-2-[([(3R,4S,5R,6R)-1,4-dimethyl-3-[(E)-2-(tributylstannyl)ethenyl]-2,9-dioxabicyclo[3.3.1]non-6-yl]carbonyl)amino]-3-methylbutanoyl]amino)-3-(3-hydroxyphenyl)propanoyl]hexahydro-3-pyridazinecarboxylate; (1S,3E)-4-iodo-1-[(E)-2-iodo-1-methylethenyl]-3-butenyl (3S)-1-[(2S)-2-([(2S)-2-[([(3R,4S,5R,6R)-1,4-dimethyl-3-[(E)-2-(tributylstannyl)ethenyl]-2,9-dioxabicyclo[3.3.1]non-6-yl]carbonyl)amino]-3-methylbutanoyl]amino)-3-(3-hydroxyphenyl)propanoyl]hexahydro-3-pyridazinecarboxylate | C50H78I2N4O8Sn | 详情 | 详情 | |
| (XXXVIII) | 32450 | (4R,7S,10S,16S,19S,25S,26R,27R)-10-(3-hydroxybenzyl)-19-[(E)-2-iodo-1-methylethenyl]-7-isopropyl-1,26-dimethyl-18,28,29-trioxa-6,9,12,30-tetraazatetracyclo[23.3.1.1(12,16).0(4,27)]triaconta-21,23-diene-5,8,11,17-tetrone; (4R,7S,10S,16S,19S,25S,26R,27R)-10-(3-hydroxybenzyl)-19-[(E)-2-iodo-1-methylethenyl]-7-isopropyl-1,26-dimethyl-18,28,29-trioxa-6,9,12,30-tetraazatetracyclo[23.3.1.1(12,16).0(4,27)]triaconta-21,23-diene-5,8,11,17-tetrone | C38H51IN4O8 | 详情 | 详情 |