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【结 构 式】 
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【分子编号】40270 【品名】tert-butyl (2S,3R,6R)-2-methyl-6-[(1R,7S)-1-[[3-(trifluoromethyl)benzoyl]oxy]-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienyl]-3-[(triisopropylsilyl)oxy]-1-piperidinecarboxylate 【CA登记号】 |
【 分 子 式 】C51H88F3NO6Si2 【 分 子 量 】924.4290696 【元素组成】C 66.26% H 9.59% F 6.17% N 1.52% O 10.38% Si 6.08% |
合成路线1
该中间体在本合成路线中的序号：(XXXVIIb)The O-silylated 4-hydroxy-delta-caprolactam (XXXIV) was reduced with borane and the resulting piperidine was protected as the N-Boc derivative (XXXV). Lithiation employing sec-butyllithium and TMEDA, followed by addition of aldehyde (XXXIII) produced an inseparable 3:1 mixture of the alcohol epimers (XXXVIIa-b) and the trans-oxazolidinone (XXXVI). Acylation of the mixture with m-(trifluoromethyl)benzoyl chloride afforded a diastereomeric mixture of (trifluoromethyl)benzoates (XXXVIIIa-b), separable by column chromatography. Deprotection of the Boc group from the syn-isomer of (XXXVIII) by means of trimethylsilyl triflate and lutidine gave the free amine (XXXIX). Subsequent cyclization of (XXXIX) with AgNO3 afforded the desired cis-quinolizidine (XL) with very high diastereoselectivity. Reductive cleavage of the (trifluoromethyl)benzoyl group of (XL), followed by treatment of the free alcohol with methanesulfonyl chloride provided mesylate (XLI).
| 【1】 Ha, J.D.; Cha, J.K.; Total synthesis of clavepictines A and B. Diastereoselective cyclization of delta-aminoallenes. J Am Chem Soc 1999, 121, 43, 10012. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 17346 | Benzyloxyacetaldehyde; 2-(Benzyloxy)acetaldehyde | 60656-87-3 | C9H10O2 | 详情 | 详情 | |
| (XXXVIIa) | 40267 | tert-butyl (2S,3R,6R)-6-[(1S,7S)-1-hydroxy-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienyl]-2-methyl-3-[(triisopropylsilyl)oxy]-1-piperidinecarboxylate | C43H85NO5Si2 | 详情 | 详情 | |
| (XXXVIIb) | 40268 | tert-butyl (2S,3R,6R)-6-[(1R,7S)-1-hydroxy-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienyl]-2-methyl-3-[(triisopropylsilyl)oxy]-1-piperidinecarboxylate | C43H85NO5Si2 | 详情 | 详情 | |
| (XXXVIIIa) | 40269 | tert-butyl (2S,3R,6R)-2-methyl-6-[(1S,7S)-1-[[3-(trifluoromethyl)benzoyl]oxy]-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienyl]-3-[(triisopropylsilyl)oxy]-1-piperidinecarboxylate | C51H88F3NO6Si2 | 详情 | 详情 | |
| (XXXVIIb) | 40270 | tert-butyl (2S,3R,6R)-2-methyl-6-[(1R,7S)-1-[[3-(trifluoromethyl)benzoyl]oxy]-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienyl]-3-[(triisopropylsilyl)oxy]-1-piperidinecarboxylate | C51H88F3NO6Si2 | 详情 | 详情 | |
| (XXXIII) | 40265 | (7S)-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienal | C23H44O2Si | 详情 | 详情 | |
| (XXXIV) | 40278 | (5R,6S)-6-methyl-5-[(triisopropylsilyl)oxy]-2-piperidinone | C15H31NO2Si | 详情 | 详情 | |
| (XXXV) | 40279 | tert-butyl (2S,3R)-2-methyl-3-[(triisopropylsilyl)oxy]-1-piperidinecarboxylate | C20H41NO3Si | 详情 | 详情 | |
| (XXXVI) | 40266 | (1R,5S,6R,8aR)-5-methyl-6-[(triisopropylsilyl)oxy]-1-[(6S)-6-[(triisopropylsilyl)oxy]-3,4-tridecadienyl]hexahydro[1,3]oxazolo[3,4-a]pyridin-3-one | C39H75NO4Si2 | 详情 | 详情 | |
| (XXXIX) | 40271 | (1R,7S)-1-[(2R,5R,6S)-6-methyl-5-[(triisopropylsilyl)oxy]piperidinyl]-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienyl 3-(trifluoromethyl)benzoate | C46H80F3NO4Si2 | 详情 | 详情 | |
| (XL) | 40272 | (1R,4S,6S,7R,9aR)-6-methyl-7-[(triisopropylsilyl)oxy]-4-[(E,3S)-3-[(triisopropylsilyl)oxy]-1-decenyl]octahydro-2H-quinolizin-1-yl 3-(trifluoromethyl)benzoate | C46H80F3NO4Si2 | 详情 | 详情 | |
| (XLI) | 40273 | (1R,4S,6S,7R,9aR)-6-methyl-7-[(triisopropylsilyl)oxy]-4-[(E,3S)-3-[(triisopropylsilyl)oxy]-1-decenyl]octahydro-2H-quinolizin-1-yl methanesulfonate | C39H79NO5SSi2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXXVIIb)The O-silylated 4-hydroxy-delta-caprolactam (XXXIV) was reduced with borane and the resulting piperidine was protected as the N-Boc derivative (XXXV). Lithiation employing sec-butyllithium and TMEDA, followed by addition of aldehyde (XXXIII) produ-ced an inseparable 3:1 mixture of the alcohol epimers (XXXVIIa-b) and the trans-oxazolidinone (XXXVI). Acylation of the mixture with m-(trifluoromethyl)benzoyl chloride afforded a diastereomeric mixture of (trifluoromethyl)benzoates (XXXVIIIa-b), separable by column chromatography. Deprotection of the Boc group from the syn-isomer of (XXXVIII) by means of trimethylsilyl triflate and lutidine gave the free amine (XXXIX). Subsequent cyclization of (XXXIX) with AgNO3 afforded the desired cis-quinolizidine (XL) with very high diastereoselectivity. Reductive cleavage of the (trifluoromethyl)benzoyl group of (XL), followed by treatment of the free alcohol with methanesulfonyl chloride provided mesylate (XLI).
| 【1】 Ha, J.D.; Cha, J.K.; Total synthesis of clavepictines A and B. Diastereoselective cyclization of delta-aminoallenes. J Am Chem Soc 1999, 121, 43, 10012. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 13746 | 3-(Trifluoromethyl)benzoyl chloride | 2251-65-2 | C8H4ClF3O | 详情 | 详情 | |
| (XXXVIIa) | 40267 | tert-butyl (2S,3R,6R)-6-[(1S,7S)-1-hydroxy-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienyl]-2-methyl-3-[(triisopropylsilyl)oxy]-1-piperidinecarboxylate | C43H85NO5Si2 | 详情 | 详情 | |
| (XXXVIIb) | 40268 | tert-butyl (2S,3R,6R)-6-[(1R,7S)-1-hydroxy-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienyl]-2-methyl-3-[(triisopropylsilyl)oxy]-1-piperidinecarboxylate | C43H85NO5Si2 | 详情 | 详情 | |
| (XXXVIIIa) | 40269 | tert-butyl (2S,3R,6R)-2-methyl-6-[(1S,7S)-1-[[3-(trifluoromethyl)benzoyl]oxy]-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienyl]-3-[(triisopropylsilyl)oxy]-1-piperidinecarboxylate | C51H88F3NO6Si2 | 详情 | 详情 | |
| (XXXVIIb) | 40270 | tert-butyl (2S,3R,6R)-2-methyl-6-[(1R,7S)-1-[[3-(trifluoromethyl)benzoyl]oxy]-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienyl]-3-[(triisopropylsilyl)oxy]-1-piperidinecarboxylate | C51H88F3NO6Si2 | 详情 | 详情 | |
| (XXXIII) | 40265 | (7S)-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienal | C23H44O2Si | 详情 | 详情 | |
| (XXXIV) | 40278 | (5R,6S)-6-methyl-5-[(triisopropylsilyl)oxy]-2-piperidinone | C15H31NO2Si | 详情 | 详情 | |
| (XXXV) | 40279 | tert-butyl (2S,3R)-2-methyl-3-[(triisopropylsilyl)oxy]-1-piperidinecarboxylate | C20H41NO3Si | 详情 | 详情 | |
| (XXXVI) | 40266 | (1R,5S,6R,8aR)-5-methyl-6-[(triisopropylsilyl)oxy]-1-[(6S)-6-[(triisopropylsilyl)oxy]-3,4-tridecadienyl]hexahydro[1,3]oxazolo[3,4-a]pyridin-3-one | C39H75NO4Si2 | 详情 | 详情 | |
| (XXXIX) | 40271 | (1R,7S)-1-[(2R,5R,6S)-6-methyl-5-[(triisopropylsilyl)oxy]piperidinyl]-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienyl 3-(trifluoromethyl)benzoate | C46H80F3NO4Si2 | 详情 | 详情 | |
| (XL) | 40272 | (1R,4S,6S,7R,9aR)-6-methyl-7-[(triisopropylsilyl)oxy]-4-[(E,3S)-3-[(triisopropylsilyl)oxy]-1-decenyl]octahydro-2H-quinolizin-1-yl 3-(trifluoromethyl)benzoate | C46H80F3NO4Si2 | 详情 | 详情 | |
| (XLI) | 40273 | (1R,4S,6S,7R,9aR)-6-methyl-7-[(triisopropylsilyl)oxy]-4-[(E,3S)-3-[(triisopropylsilyl)oxy]-1-decenyl]octahydro-2H-quinolizin-1-yl methanesulfonate | C39H79NO5SSi2 | 详情 | 详情 |