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【结 构 式】 
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【分子编号】50192 【品名】tert-butyl (4S)-5-([(1R)-1-[2-(1H-1,2,3-benzotriazol-1-yloxy)-2-oxoethyl]tetradecyl]amino)-4-[[(benzyloxy)carbonyl]amino]-5-oxopentylcarbamate 【CA登记号】 |
【 分 子 式 】C40H60N6O7 【 分 子 量 】736.95264 【元素组成】C 65.19% H 8.21% N 11.4% O 15.2% |
合成路线1
该中间体在本合成路线中的序号：(IX)Wittig reaction between aldehyde (I) and methyl(triphenylphosphoranylidene triphenyl)-acetate (II) in refluxing toluene provides E-olefin (III), which is then subjected to reaction with lithium derivative (IV) in THF to afford adduct (V). Benzyl groups of (V) are removed by hydrogenation over Pd(OH)2 in HOAc:MeOH:EtOAc to furnish amine (VI), which is then coupled to Z-Orn(Boc)-OH using 1-ethyl-3-dimethylaminopropylcarbodiimide (WSCD.HCl) and HOBt in CH2Cl2 to give beta-amino acid derivative (VIII). Saponification of the methyl ester group in (VIII) by means of LiOH, followed by condensation with HOBt by means of WSCD.HCl, yields activated ester (IX).
| 【1】 Hashimoto, S.; Hashimoto, M.; Tanaka, A.; Fujie, A.; Shigematsu, N.; Barrett, D.; An expedient synthesis of the amide analog of the potent antifungal lipopeptidolactone FR901469. Tetrahedron Lett 2001, 42, 4, 703. |
| 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) | 50186 | Myristaldehyde; Myristyl aldehyde; Tetradecanal; Myristic aldehyde trimer; Tetradecyl aldehyde | 124-25-4 | C14H28O | 详情 | 详情 |
| (II) | 14689 | Methyl (triphenylphosphoranylidene)acetate; (methoxycarbonylmethylene)triphenylphosphorane；Methyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate | 2605-67-6 | C21H19O2P | 详情 | 详情 |
| (III) | 50187 | methyl (E)-2-hexadecenoate | C17H32O2 | 详情 | 详情 | |
| (IV) | 30864 | N-Benzyl-N-(1(R)-phenylethyl)amide lithium salt | C15H16LiN | 详情 | 详情 | |
| (V) | 50188 | methyl (3R)-3-[benzyl[(1R)-1-phenylethyl]amino]hexadecanoate | C32H49NO2 | 详情 | 详情 | |
| (VI) | 50189 | methyl (3R)-3-aminohexadecanoate | C17H35NO2 | 详情 | 详情 | |
| (VII) | 50190 | (2S)-2-[[(benzyloxy)carbonyl]amino]-5-[(tert-butoxycarbonyl)amino]pentanoic acid | C18H26N2O6 | 详情 | 详情 | |
| (VIII) | 50191 | methyl (3R)-3-([(2S)-2-[[(benzyloxy)carbonyl]amino]-5-[(tert-butoxycarbonyl)amino]pentanoyl]amino)hexadecanoate | C35H59N3O7 | 详情 | 详情 | |
| (IX) | 50192 | tert-butyl (4S)-5-([(1R)-1-[2-(1H-1,2,3-benzotriazol-1-yloxy)-2-oxoethyl]tetradecyl]amino)-4-[[(benzyloxy)carbonyl]amino]-5-oxopentylcarbamate | C40H60N6O7 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)Natural peptide FR901469 (X) is incubated with Actinoplanes utahensis IFO-13244 in PBS to afford linear peptide (XI), which is then converted into precursor (XII) by coupling with activated intermediate (IX) by means of DIEA in DMF followed by removal of the Z protecting group by hydrogenation over Pd/C. Finally, the target product is obtained by macrocyclization of (XII) by means of HOBt and WSCD.HCl followed by Boc removal with neat TFA.
| 【1】 Hashimoto, S.; Hashimoto, M.; Tanaka, A.; Fujie, A.; Shigematsu, N.; Barrett, D.; An expedient synthesis of the amide analog of the potent antifungal lipopeptidolactone FR901469. Tetrahedron Lett 2001, 42, 4, 703. |
| 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) | 50192 | tert-butyl (4S)-5-([(1R)-1-[2-(1H-1,2,3-benzotriazol-1-yloxy)-2-oxoethyl]tetradecyl]amino)-4-[[(benzyloxy)carbonyl]amino]-5-oxopentylcarbamate | C40H60N6O7 | 详情 | 详情 | |
| (X) | 50193 | (3R)-3-[(2R,6S,9S,12R,15R,19R,22S,25R,31S,33aS,34S,39S,42R,44aS)-22-(3-aminopropyl)-2,34-dihydroxy-9-(4-hydroxybenzyl)-15,25,39,42-tetrakis[(1R)-1-hydroxyethyl]-6-isopropyl-12-methyl-5,8,11,14,17,21,24,27,30,33,38,41,44-tridecaoxo-19-tridecylnonatriacontahydro-1H,5H,21H-dipyrrolo[2,1-o:2,1-x][1,4,7,10,13,16,19,22,25,28,31,34,37]oxadodecaazacyclotetracontin-31-yl]-3-hydroxypropanamide | C71H116N14O23 | 详情 | 详情 | |
| (XI) | 50194 | (2R,3R)-2-[(2-[[(2S,3R)-5-amino-2-([[(2S,3S)-1-((2S,3R)-2-[[(2R,3R)-2-([[(2S,4R)-1-((2S)-2-[[(2S)-2-[((2R)-2-[[(2R,3R)-2-amino-3-hydroxybutanoyl]amino]propanoyl)amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl)-4-hydroxypyrrolidinyl]carbonyl]amino)-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl)-3-hydroxypyrrolidinyl]carbonyl]amino)-3-hydroxy-5-oxopentanoyl]amino]acetyl)amino]-3-hydroxybutyric acid | C50H78N12O21 | 详情 | 详情 | |
| (XII) | 50195 | C76H127N15O25 | 详情 | 详情 |