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【结 构 式】 
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【分子编号】40265 【品名】(7S)-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienal 【CA登记号】 |
【 分 子 式 】C23H44O2Si 【 分 子 量 】380.68666 【元素组成】C 72.57% H 11.65% O 8.41% Si 7.38% |
合成路线1
该中间体在本合成路线中的序号：(XXXIII)Sharpless asymmetric dihydroxylation of ethyl (E)-2-decenoate (XXIV) afforded diol (XXV) and subsequent regioselectively protection of the beta-alcohol with triisopropylsilyl triflate provided silyl ether (XXVI). Following protection of the remaining alcohol, as the corresponding tetrahydropyranyl ether, the ester group was converted to aldehyde (XXVII) by reduction with DIBAL and subsequent Swern oxidation. Condensation of (XXVII) with carbon tetrabromide in the presence of PPh3 gave dibromoolefin (XXVIII) which, upon treatment with butyllithium and further acidic deprotection, produced propargyl alcohol (XXIX). Orthoester-Claisen rearrangement of (XXIX) gave allene (XXX). Following reduction of (XXX) with DIBAL, the alcohol (XXXI) was subjected to one-carbon chain elongation by conversion to bromide and then displacement with NaCN. Reduction of the resulting nitrile (XXXII) with DIBAL gave the requisite aldehyde (XXXIII).
| 【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 |
|---|---|---|---|---|---|---|
| (XXIV) | 40256 | ethyl (E)-2-decenoate | 7367-88-6 | C12H22O2 | 详情 | 详情 |
| (XXV) | 40257 | ethyl (2R,3S)-2,3-dihydroxydecanoate | C12H24O4 | 详情 | 详情 | |
| (XXVI) | 40258 | ethyl (2R,3S)-2-hydroxy-3-[(triisopropylsilyl)oxy]decanoate | C21H44O4Si | 详情 | 详情 | |
| (XXVII) | 40259 | (2R,3S)-2-(tetrahydro-2H-pyran-2-yloxy)-3-[(triisopropylsilyl)oxy]decanal | C24H48O4Si | 详情 | 详情 | |
| (XXVIII) | 40260 | (1S,2S)-4,4-dibromo-1-heptyl-2-(tetrahydro-2H-pyran-2-yloxy)-3-butenyl triisopropylsilyl ether; [[(1S,2S)-4,4-dibromo-1-heptyl-2-(tetrahydro-2H-pyran-2-yloxy)-3-butenyl]oxy](triisopropyl)silane | C25H48Br2O3Si | 详情 | 详情 | |
| (XXIX) | 40261 | (3S,4S)-4-[(triisopropylsilyl)oxy]-1-undecyn-3-ol | C20H40O2Si | 详情 | 详情 | |
| (XXX) | 40262 | ethyl (6S)-6-[(triisopropylsilyl)oxy]-3,4-tridecadienoate | C24H46O3Si | 详情 | 详情 | |
| (XXXI) | 40263 | (6S)-6-[(triisopropylsilyl)oxy]-3,4-tridecadien-1-ol | C22H44O2Si | 详情 | 详情 | |
| (XXXII) | 40264 | (7S)-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienenitrile | C23H43NOSi | 详情 | 详情 | |
| (XXXIII) | 40265 | (7S)-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienal | C23H44O2Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXXIII)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3
该中间体在本合成路线中的序号：(XXXIII)Sharpless asymmetric dihydroxylation of ethyl (E)-2-decenoate (XXIV) afforded diol (XXV) and subsequent regioselectively protection of the beta-alcohol with triisopropylsilyl triflate provided silyl ether (XXVI). Following protection of the remaining alcohol, as the corresponding tetrahydropyranyl ether, the ester group was converted to aldehyde (XXVII) by reduction with DIBAL and subsequent Swern oxidation. Condensation of (XXVII) with carbon tetrabromide in the presence of PPh3 gave dibromoolefin (XXVIII) which, upon treatment with butyllithium and further acidic deprotection, produced propargyl alcohol (XXIX). Orthoester-Claisen rearrangement of (XXIX) gave allene (XXX). Following reduction of (XXX) with DIBAL, the alcohol (XXXI) was subjected to one-carbon chain elongation by conversion to bromide and then displacement with NaCN. Reduction of the resulting nitrile (XXXII) with DIBAL gave the requisite aldehyde (XXXIII).
| 【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 |
|---|---|---|---|---|---|---|
| (XXIV) | 40256 | ethyl (E)-2-decenoate | 7367-88-6 | C12H22O2 | 详情 | 详情 |
| (XXV) | 40257 | ethyl (2R,3S)-2,3-dihydroxydecanoate | C12H24O4 | 详情 | 详情 | |
| (XXVI) | 40258 | ethyl (2R,3S)-2-hydroxy-3-[(triisopropylsilyl)oxy]decanoate | C21H44O4Si | 详情 | 详情 | |
| (XXVII) | 40259 | (2R,3S)-2-(tetrahydro-2H-pyran-2-yloxy)-3-[(triisopropylsilyl)oxy]decanal | C24H48O4Si | 详情 | 详情 | |
| (XXVIII) | 40260 | (1S,2S)-4,4-dibromo-1-heptyl-2-(tetrahydro-2H-pyran-2-yloxy)-3-butenyl triisopropylsilyl ether; [[(1S,2S)-4,4-dibromo-1-heptyl-2-(tetrahydro-2H-pyran-2-yloxy)-3-butenyl]oxy](triisopropyl)silane | C25H48Br2O3Si | 详情 | 详情 | |
| (XXIX) | 40261 | (3S,4S)-4-[(triisopropylsilyl)oxy]-1-undecyn-3-ol | C20H40O2Si | 详情 | 详情 | |
| (XXX) | 40262 | ethyl (6S)-6-[(triisopropylsilyl)oxy]-3,4-tridecadienoate | C24H46O3Si | 详情 | 详情 | |
| (XXXI) | 40263 | (6S)-6-[(triisopropylsilyl)oxy]-3,4-tridecadien-1-ol | C22H44O2Si | 详情 | 详情 | |
| (XXXII) | 40264 | (7S)-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienenitrile | C23H43NOSi | 详情 | 详情 | |
| (XXXIII) | 40265 | (7S)-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienal | C23H44O2Si | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(XXXIII)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 |