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【结 构 式】 
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【分子编号】55257 【品名】(1R,2S,4S,6R,8S,10S,11R,12S,14R)-11-(benzyloxy)-8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4,14-dimethyl-5-[(Z)-phenylmethylidene]-6-[(trimethylsilyl)oxy]-15-oxatetracyclo[6.6.1.0~1,10~.0~2,6~]pentadecan-12-ol 【CA登记号】 |
【 分 子 式 】C40H60O5Si2 【 分 子 量 】677.0844 【元素组成】C 70.96% H 8.93% O 11.81% Si 8.3% |
合成路线1
该中间体在本合成路线中的序号：(XXIII)Treatment of pyranone (XIV) with DBU in boiling acetonitrile generated the pyrilium intermediate (XV) which underwent intramolecular cycloaddition to the desired endo cycloadduct (XVI). Catalytic double bond hydrogenation of enone (XVI) provided the saturated ketone (XVII). Wittig reaction of (XVII) with methylene triphenylphosphorane, followed by reacetylation with acetyl chloride furnished the exocyclic methylene derivative (XVIII). Allylic oxidation of (XVIII) by means of SeO2 and t-BuOOH, and further MnO2 oxidation of the resultant alcohol led to the methylene ketone (XIX). This was then subjected to conjugate addition of vinyl cuprate to provide ketone (XX). Diastereoselective addition of the lithium acetylide (XXI) to ketone (XX) followed by quenching with N-methyl-N-(trimethylsilyl)trifluoroacetamide furnished the silyl ether (XXII) along with some unsilylated carbinol, which was converted to (XXII) by independent silylation with chlorotrimethylsilane and imidazole. The tricyclic system (XXIII) was then obtained by zirconocene-mediated cyclization of (XXII), followed by selective acetate hydrolysis with 90 % AcOH.
| 【1】 Boger, D.L.; Searcey, M.; The first synthesis of a daphnane diterpene: The enantiocontrolled total synthesis of (+)-resiniferatoxin. Chemtracts - Org Chem 1998, 11, 9, 647. |
| 【2】 Wender, P.A.; et al.; The first synthesis of a daphnane diterpene: The enantiocontrolled total synthesis of resiniferatoxin. J Am Chem Soc 1997, 119, 52, 12976. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIV) | 55249 | 6-[(1R,3S,4R)-3-(acetyloxy)-4-(benzyloxy)-1-methyl-5-hexenyl]-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-5-oxo-5,6-dihydro-2H-pyran-2-yl acetate | C30H44O8Si | 详情 | 详情 | |
| (XV) | 55250 | 2-[(1R,3S,4R)-3-(acetyloxy)-4-(benzyloxy)-1-methyl-5-hexenyl]-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3-pyraniumolate | C28H40O6Si | 详情 | 详情 | |
| (XVI) | 55251 | (1R,2R,4S,5R,6S,8S)-5-(benzyloxy)-8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-methyl-11-oxo-12-oxatricyclo[6.3.1.0~1,6~]dodec-9-en-4-yl acetate | C28H40O6Si | 详情 | 详情 | |
| (XVII) | 55252 | (1R,2R,4S,5R,6S,8R)-5-(benzyloxy)-8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-methyl-11-oxo-12-oxatricyclo[6.3.1.0~1,6~]dodec-4-yl acetate | C28H42O6Si | 详情 | 详情 | |
| (XVIII) | 55253 | (1R,2R,4S,5R,6S,8R)-5-(benzyloxy)-8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-methyl-11-methylene-12-oxatricyclo[6.3.1.0~1,6~]dodec-4-yl acetate | C29H44O5Si | 详情 | 详情 | |
| (XIX) | 55254 | (1R,2R,4S,5R,6S,8S)-5-(benzyloxy)-8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-methyl-11-methylene-10-oxo-12-oxatricyclo[6.3.1.0~1,6~]dodec-4-yl acetate | C29H42O6Si | 详情 | 详情 | |
| (XX) | 55255 | (1R,2R,4S,5R,6S,8S,11S)-11-allyl-5-(benzyloxy)-8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-methyl-10-oxo-12-oxatricyclo[6.3.1.0~1,6~]dodec-4-yl acetate | C31H46O6Si | 详情 | 详情 | |
| (XXI) | 52731 | (2-phenylethynyl)lithium | C8H5Li | 详情 | 详情 | |
| (XXII) | 55256 | (1R,2R,4S,5R,6S,8S,10R,11S)-11-allyl-5-(benzyloxy)-8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-methyl-10-(2-phenylethynyl)-10-[(trimethylsilyl)oxy]-12-oxatricyclo[6.3.1.0~1,6~]dodec-4-yl acetate | C42H60O6Si2 | 详情 | 详情 | |
| (XXIII) | 55257 | (1R,2S,4S,6R,8S,10S,11R,12S,14R)-11-(benzyloxy)-8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4,14-dimethyl-5-[(Z)-phenylmethylidene]-6-[(trimethylsilyl)oxy]-15-oxatetracyclo[6.6.1.0~1,10~.0~2,6~]pentadecan-12-ol | C40H60O5Si2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXIII)Oxidation of alcohol (XXIII) employing tetrapropylammonium perruthenate and N-methylmorpholine-N-oxide provided ketone (XXIV). Addition of isopropenylmagnesium bromide to ketone (XXIV) occurred by the beta-face giving rise to carbinol (XXV). Subsequent ozonolysis of (XXV) produced the oxidative cleavage of both double bonds to yield diketone (XXVI). Hydrogenolysis of the O-benzyl protecting group of (XXVI) followed by reaction of the resultant diol with triphosgene furnished the cyclic carbonate (XXVII). The C20 tert-butyldimethylsilyl group of (XXVII) was selectively removed by treatment with HF to afford alcohol (XXVIII), which was further converted into alkyl iodide (XXIX) via the corresponding triflate, and then displacement with tetrabutylammonium iodide. Reductive elimination of the iodo ether moiety of (XXIX) with activated zinc afforded the exocyclic olefin (XXX).
| 【1】 Boger, D.L.; Searcey, M.; The first synthesis of a daphnane diterpene: The enantiocontrolled total synthesis of (+)-resiniferatoxin. Chemtracts - Org Chem 1998, 11, 9, 647. |
| 【2】 Wender, P.A.; et al.; The first synthesis of a daphnane diterpene: The enantiocontrolled total synthesis of resiniferatoxin. J Am Chem Soc 1997, 119, 52, 12976. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXIII) | 55257 | (1R,2S,4S,6R,8S,10S,11R,12S,14R)-11-(benzyloxy)-8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4,14-dimethyl-5-[(Z)-phenylmethylidene]-6-[(trimethylsilyl)oxy]-15-oxatetracyclo[6.6.1.0~1,10~.0~2,6~]pentadecan-12-ol | C40H60O5Si2 | 详情 | 详情 | |
| (XXIV) | 55258 | (1R,2S,4S,6R,8S,10S,11R,14R)-11-(benzyloxy)-8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4,14-dimethyl-5-[(Z)-phenylmethylidene]-6-[(trimethylsilyl)oxy]-15-oxatetracyclo[6.6.1.0~1,10~.0~2,6~]pentadecan-12-one | C40H58O5Si2 | 详情 | 详情 | |
| (XXV) | 55259 | (1R,2S,4S,6R,8S,10S,11R,12R,14R)-11-(benzyloxy)-8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-12-isopropenyl-4,14-dimethyl-5-[(Z)-phenylmethylidene]-6-[(trimethylsilyl)oxy]-15-oxatetracyclo[6.6.1.0~1,10~.0~2,6~]pentadecan-12-ol | C43H64O5Si2 | 详情 | 详情 | |
| (XXVI) | 55260 | (1R,2S,4S,6R,8S,10S,11R,12S,14R)-12-acetyl-11-(benzyloxy)-8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-12-hydroxy-4,14-dimethyl-6-[(trimethylsilyl)oxy]-15-oxatetracyclo[6.6.1.0~1,10~.0~2,6~]pentadecan-5-one | C35H56O7Si2 | 详情 | 详情 | |
| (XXVII) | 55261 | (1R,2R,4S,8R,9S,11S,13R,15S,17S)-4-acetyl-11-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2,15-dimethyl-13-[(trimethylsilyl)oxy]-5,7,18-trioxapentacyclo[9.6.1.0~1,9~.0~4,8~.0~13,17~]octadecane-6,14-dione | C29H48O8Si2 | 详情 | 详情 | |
| (XXVIII) | 55262 | (1R,2R,4S,8R,9S,11S,13R,15S,17S)-4-acetyl-11-(hydroxymethyl)-2,15-dimethyl-13-[(trimethylsilyl)oxy]-5,7,18-trioxapentacyclo[9.6.1.0~1,9~.0~4,8~.0~13,17~]octadecane-6,14-dione | C23H34O8Si | 详情 | 详情 | |
| (XXIX) | 55263 | (1R,2R,4S,8R,9S,11S,13R,15S,17S)-4-acetyl-11-(iodomethyl)-2,15-dimethyl-13-[(trimethylsilyl)oxy]-5,7,18-trioxapentacyclo[9.6.1.0~1,9~.0~4,8~.0~13,17~]octadecane-6,14-dione | C23H33IO7Si | 详情 | 详情 | |
| (XXX) | 55264 | (3aR,3bS,6aR,8S,9aS,9bR,10R,11aS)-11a-acetyl-9b-hydroxy-8,10-dimethyl-5-methylene-6a-[(trimethylsilyl)oxy]dodecahydroazuleno[5,4-e][1,3]benzodioxole-2,7(3aH)-dione | C23H34O7Si | 详情 | 详情 |