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【结 构 式】 
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【分子编号】16119 【品名】4''-(Pentyloxy)-p-terphenyl-4-carboxylic acid 2,4,5-trichlorophenyl ester 【CA登记号】 |
【 分 子 式 】C30H25Cl3O3 【 分 子 量 】539.8848 【元素组成】C 66.74% H 4.67% Cl 19.7% O 8.89% |
合成路线1
该中间体在本合成路线中的序号：(II)By condensation of cyclopeptide (I) with 4''-(pentyloxy)-p-terphenyl-4-carboxylic acid 2,4,5-trichlorophenyl ester (II) by means of dicyclohexylcarbodiimide (DCC) in DMF at room temperature.
| 【1】 Burkhardt, F.J.; Debono, M.; Nissen, J.S.; Turner, W.W. Jr. (Eli Lilly and Company); Cyclic peptide antifungal agents and process for preparation thereof. EP 0561639; JP 1994056892 . |
| 【2】 Fromtling, R.A.; LY-303366. Drugs Fut 1994, 19, 4, 338. |
| 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) | 16118 | (2R,6S,9S,11R,12R,14aS,15S,16S,20S,23S,25aS)-9-amino-23-[(1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-2,11,12,15-tetrahydroxy-6,20-bis[(1R)-1-hydroxyethyl]-16-methylhexadecahydro-1H-dipyrrolo[2,1-c:2,1-l][1,4,7,10,13,16]hexaazacyclohenicosine-5,8,14,19,22,25(9H,25aH)-hexone | C34H51N7O15 | 详情 | 详情 | |
| (II) | 16119 | 4''-(Pentyloxy)-p-terphenyl-4-carboxylic acid 2,4,5-trichlorophenyl ester | C30H25Cl3O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)A new synthesis of LY-303366 has been reported: The enzymatic hydrolysis of echinocandin B (I) with Actinoplanes utahensis provides the corresponding cyclic peptide (II), which is then reacylated with the active ester 4''-(pentyloxy)-p-terphenyl-4-carboxylic acid 2,4,5-trichlorophenyl ester (III) in DMF. The active ester (III) is obtained as follows: 4-Bromo-4'-(pentyloxy)biphenyl (IV) is treated with sec-butyllithium and triisopropyl borate in THF/cyclohexane, yielding (after hydrolysis with HCl) 4'-(pentyloxy)biphenyl-4-boronic acid (V), which is condensed with methyl 4-iodobenzoate (VI) by means of palladium tetrakis(triphenylphosphine) and K2CO3 in refluxing toluene, giving 4''-(pentyloxy)-p-terphenyl-4-carboxylic acid methyl ester (VII). The hydrolysis of (VII) with NaOH in refluxing dioxane containing 2N NaOH affords the corresponding free acid (VIII), which is finally converted to the active ester (III) by esterification with 2,4,5-trichlorophenol (IX) by means of dicyclohexylcarbodiimide (DCC) in DMF.
| 【1】 LaGrandeur, L.; Turner, W.W.; Debono, M.; et al.; Semisynthetic chemical modification of the antifungal lipopeptidechinocandin B (ECB): Structure-activity studies of the lipophilic and geometric parameters of polyarylated acyl analogs of ECB. J Med Chem 1995, 38, 17, 3271. |
| 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) | 16120 | (9Z,12Z)-N-[(2R,6S,9S,11R,12R,14aS,15S,16S,20S,23S,25aS)-23-[(1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-2,11,12,15-tetrahydroxy-6,20-bis[(1R)-1-hydroxyethyl]-16-methyl-5,8,14,19,22,25-hexaoxotetracosahydro-1H-dipyrrolo[2,1-c:2,1-l][1,4,7,10,13,16]hexaazacyclohenicosin-9-yl]-9,12-octadecadienamide | C52H81N7O16 | 详情 | 详情 | |
| (II) | 16118 | (2R,6S,9S,11R,12R,14aS,15S,16S,20S,23S,25aS)-9-amino-23-[(1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-2,11,12,15-tetrahydroxy-6,20-bis[(1R)-1-hydroxyethyl]-16-methylhexadecahydro-1H-dipyrrolo[2,1-c:2,1-l][1,4,7,10,13,16]hexaazacyclohenicosine-5,8,14,19,22,25(9H,25aH)-hexone | C34H51N7O15 | 详情 | 详情 | |
| (III) | 16119 | 4''-(Pentyloxy)-p-terphenyl-4-carboxylic acid 2,4,5-trichlorophenyl ester | C30H25Cl3O3 | 详情 | 详情 | |
| (IV) | 16121 | 4-bromo-4'-(pentyloxy)-1,1'-biphenyl; 4'-bromo[1,1'-biphenyl]-4-yl pentyl ether | C17H19BrO | 详情 | 详情 | |
| (V) | 16122 | 4'-(Pentyloxy)biphenyl-4-ylboronic acid | C17H21BO4 | 详情 | 详情 | |
| (VI) | 16123 | methyl 4-iodobenzoate | 619-44-3 | C8H7IO2 | 详情 | 详情 |
| (VII) | 16124 | 4''-Pentyloxy-p-terphenyl-4-carboxylic acid methyl ester | C25H26O3 | 详情 | 详情 | |
| (VIII) | 16125 | 4''-(Pentyloxy)-p-terphenyl-4-carboxylic acid | C24H24O3 | 详情 | 详情 | |
| (IX) | 16126 | 2,4,5-trichlorophenol | 95-95-4 | C6H3Cl3O | 详情 | 详情 |