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【结 构 式】 
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【分子编号】27414 【品名】(2E,6E)-1-bromo-3,7,11-trimethyl-2,6,10-dodecatriene 【CA登记号】 |
【 分 子 式 】C15H25Br 【 分 子 量 】285.2675 【元素组成】C 63.16% H 8.83% Br 28.01% |
合成路线1
该中间体在本合成路线中的序号：(II)The reaction of L-cysteine methyl ester (I) with farnesyl bromide (II) by means of ammonia in methanol gives the S-derivative (III), which is Boc protected as usual yielding the protected cysteine (IV). The reduction of (IV) with diisobutylaluminum hydride in toluene affords the cysteine aldehyde (V), which is reductocondensed with the tripeptide L-valine-L-isoleucine-L-methionine methyl ester (VI) by means of sodium cyanoborohydride in acidic methanol giving the peptide ester (VII). Finally, this compound is hydrolyzed with barium hydroxide in methanol/water.
| 【1】 Rando, R.R. (Harvard College); Cpds. for inhibition of proteolysis. WO 9401126 . |
| 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) | 27413 | methyl (2R)-2-amino-3-sulfanylpropanoate | C4H9NO2S | 详情 | 详情 | |
| (II) | 27414 | (2E,6E)-1-bromo-3,7,11-trimethyl-2,6,10-dodecatriene | C15H25Br | 详情 | 详情 | |
| (III) | 27415 | methyl (2R)-2-amino-3-[[(2E,6E)-3,7,11-trimethyl-2,6,10-dodecatrienyl]sulfanyl]propanoate | C19H33NO2S | 详情 | 详情 | |
| (IV) | 27416 | methyl (2R)-2-[(tert-butoxycarbonyl)amino]-3-[[(2E,6E)-3,7,11-trimethyl-2,6,10-dodecatrienyl]sulfanyl]propanoate | C24H41NO4S | 详情 | 详情 | |
| (V) | 27417 | tert-butyl (1R)-1-formyl-2-[[(2E,6E)-3,7,11-trimethyl-2,6,10-dodecatrienyl]sulfanyl]ethylcarbamate | C23H39NO3S | 详情 | 详情 | |
| (VI) | 27418 | methyl (2S)-2-[((2S,3S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-methylpentanoyl)amino]-4-(methylsulfanyl)butanoate | C17H33N3O4S | 详情 | 详情 | |
| (VII) | 27419 | methyl (6R,9S,12S,15S)-9-isopropyl-2,2-dimethyl-12-[(1S)-1-methylpropyl]-15-[2-(methylsulfanyl)ethyl]-4,10,13-trioxo-6-([[(2E,6E)-3,7,11-trimethyl-2,6,10-dodecatrienyl]sulfanyl]methyl)-3-oxa-5,8,11,14-tetraazahexadecan-16-oate | C40H72N4O6S2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The alkylation of N-acetyl-L-cysteine (I) with farnesyl bromide (II) in methanolic ammonia provided the corresponding farnesyl thioether (III). After activation of the S-alkylated acid (III) as the mixed anhydride (IV) using isobutyl chloroformate and N-methylmorpholine, reaction with diazomethane yielded the diazomethyl ketone (V). This was then converted into the title chloromethyl ketone by treatment with HCl in ethyl acetate.
| 【1】 Narla, R.K.; Uckun, F.M.; Perrey, D.A.; Cysteine chloromethyl and diazomethyl ketone derivatives with potent anti-leukemic activity. Bioorg Med Chem Lett 2000, 10, 6, 547. |
| 【2】 Narla, R.K.; Uckun, F.M.; Perry, D.A. (Parker Hughes Institute); Alkyl ketones as potent anti-cancer agents. WO 0000469 . |
| 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) | 43592 | (2R)-2-(acetamido)-3-sulfanylpropionic acid | C5H9NO3S | 详情 | 详情 | |
| (II) | 27414 | (2E,6E)-1-bromo-3,7,11-trimethyl-2,6,10-dodecatriene | C15H25Br | 详情 | 详情 | |
| (III) | 44902 | (2R)-2-(acetamido)-3-[[(2E,6E)-3,7,11-trimethyl-2,6,10-dodecatrienyl]sulfanyl]propionic acid | 135304-07-3 | C20H33NO3S | 详情 | 详情 |
| (IV) | 44903 | C25H41NO5S | 详情 | 详情 | ||
| (V) | 44904 | C21H33N3O2S | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)By condensation ot piperonylpiperazine (I) with 1-bromo-3,7,11-trimethyl-2,6,10-dodecatriene (II) by means of triethylamine in benzene.
| 【1】 Bianchetti, A.; Samaritan advances HIV pipeline. Eur J Med Chem - Chim Ther 1974, 9, 555. |
| 【2】 Castaner, J.; de Angelis, L.; Pifazine. Drugs Fut 1976, 1, 7, 354. |