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【结 构 式】 
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【分子编号】55264 【品名】(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 【CA登记号】 |
【 分 子 式 】C23H34O7Si 【 分 子 量 】450.60426 【元素组成】C 61.31% H 7.61% O 24.85% Si 6.23% |
合成路线1
该中间体在本合成路线中的序号：(XXX)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 |
合成路线2
该中间体在本合成路线中的序号：(XXX)Allylic oxidation of olefin (XXX) with SeO2 and t-BuOOH led to the formation of the desired C7 alcohol (XXXI) along with the C5 regioisomer (XXXII). Chlorination of the allylic alcohol (XXXI) with SOCl2, followed by nucleophilic displacement by benzoate gave the C-20 benzoate (XXXIII). Selective hydrolysis of the cyclic carbonate of (XXXIII) with 0.5 M NaOH furnished the glycol derivative (XXXIV). Coupling of (XXXIV) with the mixed anhydride (XXXV) produced only the C14 phenylacetate ester (XXXVI). This underwent further cyclization with the free hydroxyl groups to the orthoester compound (XXXVII) under mild acidic conditions. The isopropenyl group was regenerated by a Peterson olefination of the C15 ketone of (XXXVII) to provide (XXXVIII). The benzoyl group was then reintroduced in (XXXVIII) at C20 yielding (XXXIX).
| 【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 |
|---|---|---|---|---|---|---|
| (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 | |
| (XXXI) | 55265 | (3aR,3bS,4R,6aR,8S,9aS,9bR,10R,11aS)-11a-acetyl-4,9b-dihydroxy-8,10-dimethyl-5-methylene-6a-[(trimethylsilyl)oxy]dodecahydroazuleno[5,4-e][1,3]benzodioxole-2,7(3aH)-dione | C23H34O8Si | 详情 | 详情 | |
| (XXXII) | 55266 | (3aR,3bS,6R,6aS,8S,9aS,9bR,10R,11aS)-11a-acetyl-6,9b-dihydroxy-8,10-dimethyl-5-methylene-6a-[(trimethylsilyl)oxy]dodecahydroazuleno[5,4-e][1,3]benzodioxole-2,7(3aH)-dione | C23H34O8Si | 详情 | 详情 | |
| (XXXIII) | 55267 | {(3aR,3bS,6aR,8S,9aS,9bR,10R,11aS)-11a-acetyl-9b-hydroxy-8,10-dimethyl-2,7-dioxo-6a-[(trimethylsilyl)oxy]-3a,3b,6,6a,7,8,9,9a,9b,10,11,11a-dodecahydroazuleno[5,4-e][1,3]benzodioxol-5-yl}methyl benzoate | C30H38O9Si | 详情 | 详情 | |
| (XXXIV) | 55268 | {(2S,3aR,6aS,7R,8S,10R,10aR,10bS)-8-acetyl-7,8,10a-trihydroxy-2,10-dimethyl-3-oxo-3a-[(trimethylsilyl)oxy]-1,2,3,3a,4,6a,7,8,9,10,10a,10b-dodecahydrobenzo[e]azulen-5-yl}methyl benzoate | C29H40O8Si | 详情 | 详情 | |
| (XXXV) | 55269 | phenylacetic 2,4,6-trichloro-1-benzenecarboxylic anhydride | C15H9Cl3O3 | 详情 | 详情 | |
| (XXXVI) | 55270 | {(2S,3aR,6aS,7R,8S,10R,10aR,10bS)-8-acetyl-8,10a-dihydroxy-2,10-dimethyl-3-oxo-7-[(2-phenylacetyl)oxy]-3a-[(trimethylsilyl)oxy]-1,2,3,3a,4,6a,7,8,9,10,10a,10b-dodecahydrobenzo[e]azulen-5-yl}methyl benzoate | C37H46O9Si | 详情 | 详情 | |
| (XXXVII) | 55271 | {(1R,2S,4S,6R,10S,11R,13S,15S,17R)-15-acetyl-13-benzyl-4,17-dimethyl-5-oxo-6-[(trimethylsilyl)oxy]-12,14,18-trioxapentacyclo[11.4.1.0~1,10~.0~2,6~.0~11,15~]octadec-8-en-8-yl}methyl benzoate | C37H44O8Si | 详情 | 详情 | |
| (XXXVIII) | 55272 | (1R,2S,4S,6R,10S,11R,13S,15R,17R)-13-benzyl-8-(hydroxymethyl)-15-isopropenyl-4,17-dimethyl-6-[(trimethylsilyl)oxy]-12,14,18-trioxapentacyclo[11.4.1.0~1,10~.0~2,6~.0~11,15~]octadec-8-en-5-one | C31H42O6Si | 详情 | 详情 | |
| (XXXIX) | 55273 | {(1R,2S,4S,6R,10S,11R,13S,15R,17R)-13-benzyl-15-isopropenyl-4,17-dimethyl-5-oxo-6-[(trimethylsilyl)oxy]-12,14,18-trioxapentacyclo[11.4.1.0~1,10~.0~2,6~.0~11,15~]octadec-8-en-8-yl}methyl benzoate | C38H46O7Si | 详情 | 详情 |