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【结 构 式】 
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【分子编号】55273 【品名】{(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 【CA登记号】 |
【 分 子 式 】C38H46O7Si 【 分 子 量 】642.86454 【元素组成】C 71% H 7.21% O 17.42% Si 4.37% |
合成路线1
该中间体在本合成路线中的序号：(XXXIX)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 |
合成路线2
该中间体在本合成路线中的序号：(XXXIX)Bromination at the alpha-position of ketone (XXXIX) to (XLI) was effected via formation of the corresponding silyl enol ether (XL), followed by treatment with N-bromosuccinimide. Dehydrohalogenation of the resultant bromo ketone (XLI) by means of lithium carbonate and lithium bromide in hot DMF afforded enone (XLII). Sequential removal of the O-silyl and benzoate protecting groups of (XLII) provided diol (XLIII). The C20 alcohol of (XLIII) was then esterified with the mixed anhydride (XLIV) to furnish the (4-O-acetyl)homovanillic ester (XLV). Finally, a soultion of pyrrolidine in CH2Cl2 was employed for the cleavage of the O-acetyl protecting group of (XLV).
| 【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 |
|---|---|---|---|---|---|---|
| (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 | |
| (XL) | 55274 | {(1R,2S,6R,10S,11R,13S,15R,17R)-13-benzyl-15-isopropenyl-4,17-dimethyl-5,6-bis[(trimethylsilyl)oxy]-12,14,18-trioxapentacyclo[11.4.1.0~1,10~.0~2,6~.0~11,15~]octadeca-4,8-dien-8-yl}methyl benzoate | C41H54O7Si2 | 详情 | 详情 | |
| (XLI) | 55275 | {(1R,2S,6R,10S,11R,13S,15R,17R)-13-benzyl-4-bromo-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 | C38H45BrO7Si | 详情 | 详情 | |
| (XLII) | 55276 | {(1R,2S,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~]octadeca-3,8-dien-8-yl}methyl benzoate | C38H44O7Si | 详情 | 详情 | |
| (XLIII) | 55277 | (1R,2R,6R,10S,11R,13S,15R,17R)-13-benzyl-6-hydroxy-8-(hydroxymethyl)-15-isopropenyl-4,17-dimethyl-12,14,18-trioxapentacyclo[11.4.1.0~1,10~.0~2,6~.0~11,15~]octadeca-3,8-dien-5-one | C28H32O6 | 详情 | 详情 | |
| (XLIV) | 55278 | [4-(acetyloxy)-3-methoxyphenyl]acetic 2,4,6-trichloro-1-benzenecarboxylic anhydride | C18H13Cl3O6 | 详情 | 详情 | |
| (XLV) | 55279 | [(1R,2R,6R,10S,11R,13S,15R,17R)-13-benzyl-6-hydroxy-15-isopropenyl-4,17-dimethyl-5-oxo-12,14,18-trioxapentacyclo[11.4.1.0~1,10~.0~2,6~.0~11,15~]octadeca-3,8-dien-8-yl]methyl 2-[4-(acetyloxy)-3-methoxyphenyl]acetate | C39H42O10 | 详情 | 详情 |