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【结 构 式】 
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【分子编号】31364 【品名】(5E)-2-[(Z,4E)-6-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4-methyl-4-hexenylidene]-6,10-dimethyl-5,9-undecadienal 【CA登记号】 |
【 分 子 式 】C28H35NO3 【 分 子 量 】433.59084 【元素组成】C 77.56% H 8.14% N 3.23% O 11.07% |
合成路线1
该中间体在本合成路线中的序号：(IX)The alkylation of ethyl 4,4-diethoxyacetoacetate (I) with geranyl bromide (II) gave ketoester (III), which was further decarbethoxylated upon treatment with KOH in refluxing H2O - EtOH yielding (IV). Wittig condensation of the resulting alpha-acetal ketone (IV) with phosphonium salt (V) in the presence of KH and crown ether provided the Z olefin (VI) as the major isomer. Deprotection of the silyl ether of (VI) with tetrabutylammonium fluoride gave alcohol (VII), which was coupled with phthalimide under Mitsunobu conditions to yield (VIII). Hydrolysis of the acetal group of (VIII) with aqueous AcOH gave aldehyde (IX).
| 【1】 Masuda, K.; Akiyama, T.; Tago, K.; Arai, M.; Minami, E.; Kogen, H.; A highly stereoselective synthesis of plaunotol and its thiourea derivatives as potent antibacterial agents against Helicobacter pylori. Bioorg Med Chem Lett 1999, 9, 10, 1347. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 31358 | ethyl 4,4-diethoxy-3-oxobutanoate | C10H18O5 | 详情 | 详情 | |
| (II) | 31116 | (2E)-1-bromo-3,7-dimethyl-2,6-octadiene; trans-Geranyl bromide; Geranyl bromide | 6138-90-5 | C10H17Br | 详情 | 详情 |
| (III) | 31359 | ethyl (4E)-2-(2,2-diethoxyacetyl)-5,9-dimethyl-4,8-decadienoate | C20H34O5 | 详情 | 详情 | |
| (IV) | 31360 | (5E)-1,1-diethoxy-6,10-dimethyl-5,9-undecadien-2-one | C17H30O3 | 详情 | 详情 | |
| (V) | 31361 | ((E)-6-[[tert-butyl(dimethyl)silyl]oxy]-4-methyl-4-hexenyl)(triphenyl)phosphonium iodide | C31H42IOPSi | 详情 | 详情 | |
| (VI) | 31365 | tert-butyl[[(2E,6Z,10E)-7-(diethoxymethyl)-3,11,15-trimethyl-2,6,10,14-hexadecatetraenyl]oxy]dimethylsilane; tert-butyl(dimethyl)silyl (2E,6Z,10E)-7-(diethoxymethyl)-3,11,15-trimethyl-2,6,10,14-hexadecatetraenyl ether | C30H56O3Si | 详情 | 详情 | |
| (VII) | 31362 | (2E,6Z,10E)-7-(diethoxymethyl)-3,11,15-trimethyl-2,6,10,14-hexadecatetraen-1-ol | C24H42O3 | 详情 | 详情 | |
| (VIII) | 31363 | 2-[(2E,6Z,10E)-7-(diethoxymethyl)-3,11,15-trimethyl-2,6,10,14-hexadecatetraenyl]-1H-isoindole-1,3(2H)-dione | C32H45NO4 | 详情 | 详情 | |
| (IX) | 31364 | (5E)-2-[(Z,4E)-6-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4-methyl-4-hexenylidene]-6,10-dimethyl-5,9-undecadienal | C28H35NO3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)Then, selective reduction of the aldehyde by treatment with zinc borohydride produced alcohol (X). Deprotection of the phthalimide group of (X) with butylamine gave primary amine (XI). This was finally converted to the target thiourea by treatment with phenethyl isocyanate (XII) in EtOH.
| 【1】 Masuda, K.; Akiyama, T.; Tago, K.; Arai, M.; Minami, E.; Kogen, H.; A highly stereoselective synthesis of plaunotol and its thiourea derivatives as potent antibacterial agents against Helicobacter pylori. Bioorg Med Chem Lett 1999, 9, 10, 1347. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 31364 | (5E)-2-[(Z,4E)-6-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4-methyl-4-hexenylidene]-6,10-dimethyl-5,9-undecadienal | C28H35NO3 | 详情 | 详情 | |
| (X) | 31366 | 2-[(2E,6Z,10E)-7-(hydroxymethyl)-3,11,15-trimethyl-2,6,10,14-hexadecatetraenyl]-1H-isoindole-1,3(2H)-dione | C28H37NO3 | 详情 | 详情 | |
| (XI) | 31367 | (5E)-2-[(Z,4E)-6-amino-4-methyl-4-hexenylidene]-6,10-dimethyl-5,9-undecadien-1-ol | C20H35NO | 详情 | 详情 | |
| (XII) | 31368 | phenethyl isothiocyanate; 1-(2-isothiocyanatoethyl)benzene | 2257-09-2 | C9H9NS | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(V)Treatment of 1,2,5,6-diisopropylidene-D-glucofuranose (I) with trifluoromethanesulfonic anhydride and pyridine provides triflate (II), which is then displaced with sodium azide to furnish the 3-azido derivative (III). Oxidative cleavage of the 5,6-diol acetonide of (III) by means of periodic acid leads to aldehyde (IV). Further oxidation of (IV) with a catalytic amount of ruthenium trichloride in the presence of sodium periodate affords carboxylic acid (V). After activation of acid (V) with oxalyl chloride, coupling with methylamine provides amide (VI). Acidic hydrolysis of the remaining 1,2-acetonide of (VI) in the presence of acetic anhydride gives rise to diacetate (VII). Silylation of 6-chloropurine (VIII), followed by coupling with the diacetyl ribofuranuronic acid derivative (VII) in the presence of trimethylsilyl triflate yields the purine glycoside (IX). The acetate ester group of (IX) is then removed by methanolysis in the presence of either methylamine or triethylamine, to produce alcohol (X). Subsequent azido group reduction in (X) by means of triphenylphosphine leads to amine (XI), which is then protected as the N-Boc derivative (XII) employing di-t-butyl dicarbonate.
| 【1】 Masamune, H.; Scott, R.W.; Deninno, M.P. (Pfizer Products Inc.); Cpds. for the treatment of ischemia. EP 1216257; JP 2003510331; WO 0123399 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 29141 | (3aR,5S,6S,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol | 582-52-5 | C12H20O6 | 详情 | 详情 |
| (II) | 61299 | (3aR,5R,6S,6aR)-5-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl trifluoromethanesulfonate | C13H19F3O8S | 详情 | 详情 | |
| (III) | 61300 | (3aR,5S,6R,6aR)-5-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl azide; (3aR,5S,6R,6aR)-6-azido-5-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole | C12H19N3O5 | 详情 | 详情 | |
| (IV) | 61363 | (3aR,5S,6R,6aR)-6-azido-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole-5-carbaldehyde | C8H11N3O4 | 详情 | 详情 | |
| (V) | 31364 | (5E)-2-[(Z,4E)-6-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4-methyl-4-hexenylidene]-6,10-dimethyl-5,9-undecadienal | C28H35NO3 | 详情 | 详情 | |
| (VI) | 31365 | tert-butyl[[(2E,6Z,10E)-7-(diethoxymethyl)-3,11,15-trimethyl-2,6,10,14-hexadecatetraenyl]oxy]dimethylsilane; tert-butyl(dimethyl)silyl (2E,6Z,10E)-7-(diethoxymethyl)-3,11,15-trimethyl-2,6,10,14-hexadecatetraenyl ether | C30H56O3Si | 详情 | 详情 | |
| (VII) | 31366 | 2-[(2E,6Z,10E)-7-(hydroxymethyl)-3,11,15-trimethyl-2,6,10,14-hexadecatetraenyl]-1H-isoindole-1,3(2H)-dione | C28H37NO3 | 详情 | 详情 | |
| (VIII) | 17692 | 6-Chloropurine; 6-chloro-9H-purine | 87-42-3 | C5H3ClN4 | 详情 | 详情 |
| (IX) | 61367 | (2R,3R,4R,5S)-4-azido-2-(6-chloro-9H-purin-9-yl)-5-[(methylamino)carbonyl]tetrahydro-3-furanyl acetate | C13H13ClN8O4 | 详情 | 详情 | |
| (X) | 61368 | (2S,3S,4R,5R)-3-azido-5-(6-chloro-9H-purin-9-yl)-4-hydroxy-N-methyltetrahydro-2-furancarboxamide | C11H11ClN8O3 | 详情 | 详情 | |
| (XI) | 61369 | (2S,3S,4R,5R)-3-amino-5-(6-chloro-9H-purin-9-yl)-4-hydroxy-N-methyltetrahydro-2-furancarboxamide | C11H13ClN6O3 | 详情 | 详情 | |
| (XII) | 61370 | tert-butyl (2S,3S,4R,5R)-5-(6-chloro-9H-purin-9-yl)-4-hydroxy-2-[(methylamino)carbonyl]tetrahydro-3-furanylcarbamate | C16H21ClN6O5 | 详情 | 详情 |