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【结 构 式】 
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【分子编号】35371 【品名】(2R,3S,7R,9R,10R,11R,12S,13R)-10-[[(1R,2R,3S,5R)-2-(acetoxy)-3-(dimethylamino)-5-methylcyclohexyl]oxy]-2-ethyl-9-methoxy-3,5,7,9,11,13-hexamethyl-6,14-dioxo-12-[[2-(2-pyridinyl)acetyl]oxy]oxa-4-cyclotetradecen-3-yl 1H-imidazole-1-carboxylate 【CA登记号】 |
【 分 子 式 】C44H64N4O11 【 分 子 量 】825.01252 【元素组成】C 64.06% H 7.82% N 6.79% O 21.33% |
合成路线1
该中间体在本合成路线中的序号：(XV)The selective hydrolysis of clarithromycin (I) with aqueous HCl, followed by acylation with acetic anhydride gives the monoacetylated descladinosyl compound (XI), which by reaction with trichloromethyl chloroformate (TCF) yields the cyclic carbonate (XII). The reaction of (XII) with 1,1,3,3-tetramethylguanidine (TMG) affords intermediate (XIII), which is selecti-ely acylated with 2-(2-pyridyl)acetic acid (X) and WSC giving the 3-O-acylated compound (XIV). The activation of (XIV) with CDI affords the 12-O-imidazolylcarbonyl derivative (XV), which is cyclized with ethylenediamine (IV) providing the carbamate (XVI). The alkylation of the primary amine of (XVI) by reductocondensation with pyridine-3-carbaldehyde (VI) and NaBH(OAc)3 gives the secondary amine (XVII).
| 【1】 Tanikawa, T.; Akashi, T.; Manaka, A.; Suzuki, K.; Asaka, T.; Adachi, T.; Ishii, T.; Sugiyama, H.; Kashimura, M.; Saito, H.; Morimoto, S.; Structure activity studies leading potent acyclides: 3-O-Acyl-5-O-desosaminylerythronolide 11,12-carbamates. 39th Intersci Conf Antimicrob Agents Chemother (Sept 26 1999, San Francisco) 1999, Abst F2159. |
| 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) | 35358 | C39H71NO12 | 详情 | 详情 | ||
| (IV) | 14754 | ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine | 107-15-3 | C2H8N2 | 详情 | 详情 |
| (VI) | 35374 | 5,6-dihydro-3-pyridinecarbaldehyde | C6H7NO | 详情 | 详情 | |
| (X) | 35369 | (1R,2S,4R,6R)-2-(dimethylamino)-6-[[(3R,4S,5S,6R,7R,9R,13S,14R)-14-ethyl-4,13-dihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,10-dioxooxa-11-cyclotetradecen-6-yl]oxy]-4-methylcyclohexyl acetate | C33H57NO9 | 详情 | 详情 | |
| (XI) | 35367 | (1R,2S,4R,6R)-2-(dimethylamino)-6-[[(3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-14-ethyl-4,12,13-trihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,10-dioxooxacyclotetradecanyl]oxy]-4-methylcyclohexyl acetate | C33H59NO10 | 详情 | 详情 | |
| (XII) | 35368 | (1R,2R,4R,6S)-2-[[(3aR,4R,7R,8S,9S,10R,11R,13R,15R,15aR)-4-ethyl-8-hydroxy-11-methoxy-3a,7,9,11,13,15-hexamethyl-2,6,14-trioxododecahydro-4H-[1,3]dioxolo[4,5-c]oxacyclotetradecin-10-yl]oxy]-6-(dimethylamino)-4-methylcyclohexyl acetate | C34H57NO11 | 详情 | 详情 | |
| (XIII) | 35366 | 2-(2-pyridinyl)acetic acid | 16179-97-8 | C7H7NO2 | 详情 | 详情 |
| (XIV) | 35370 | (3R,4S,5R,6R,7R,9R,13S,14R)-6-[[(1R,2R,3S,5R)-2-(acetoxy)-3-(dimethylamino)-5-methylcyclohexyl]oxy]-14-ethyl-13-hydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,10-dioxooxa-11-cyclotetradecen-4-yl 2-(2-pyridinyl)acetate | C40H62N2O10 | 详情 | 详情 | |
| (XV) | 35371 | (2R,3S,7R,9R,10R,11R,12S,13R)-10-[[(1R,2R,3S,5R)-2-(acetoxy)-3-(dimethylamino)-5-methylcyclohexyl]oxy]-2-ethyl-9-methoxy-3,5,7,9,11,13-hexamethyl-6,14-dioxo-12-[[2-(2-pyridinyl)acetyl]oxy]oxa-4-cyclotetradecen-3-yl 1H-imidazole-1-carboxylate | C44H64N4O11 | 详情 | 详情 | |
| (XVI) | 35372 | C43H68N4O11 | 详情 | 详情 | ||
| (XVII) | 35378 | C49H73N5O11 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XV)The selective hydrolysis of clarithromycin (I) with aqueous HCl, followed by acylation with acetic anhydride gives the monoacetylated descladinosyl compound (XI), which by reaction with trichloromethyl chloroformate (TCF) yields the cyclic carbonate (XII). The reaction of (XII) with 1,1,3,3-tetramethylguanidine (TMG) affords intermediate (XIII), which is selectively acylated with 2-(2-pyridyl)acetic acid (X) and WSC giving the 3-O-acylated compound (XIV). The activation of (XIV) with CDI affords the 12-O-imidazolylcarbonyl derivative (XV), which is cyclized with ethylenediamine (IV) providing the carbamate (XVI). The alkylation of the primary amine of (XVI) by reductocondensation with quinoline-3-carbaldehyde (VI) and NaBH(OAc)3 gives the secondary amine (XVII).
| 【1】 Tanikawa, T.; Akashi, T.; Manaka, A.; Suzuki, K.; Asaka, T.; Adachi, T.; Ishii, T.; Sugiyama, H.; Kashimura, M.; Saito, H.; Morimoto, S.; Structure activity studies leading potent acyclides: 3-O-Acyl-5-O-desosaminylerythronolide 11,12-carbamates. 39th Intersci Conf Antimicrob Agents Chemother (Sept 26 1999, San Francisco) 1999, Abst F2159. |
| 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) | 35358 | C39H71NO12 | 详情 | 详情 | ||
| (IV) | 14754 | ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine | 107-15-3 | C2H8N2 | 详情 | 详情 |
| (VI) | 35362 | 3-quinolinecarbaldehyde | 13669-42-6 | C10H7NO | 详情 | 详情 |
| (X) | 35369 | (1R,2S,4R,6R)-2-(dimethylamino)-6-[[(3R,4S,5S,6R,7R,9R,13S,14R)-14-ethyl-4,13-dihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,10-dioxooxa-11-cyclotetradecen-6-yl]oxy]-4-methylcyclohexyl acetate | C33H57NO9 | 详情 | 详情 | |
| (XI) | 35367 | (1R,2S,4R,6R)-2-(dimethylamino)-6-[[(3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-14-ethyl-4,12,13-trihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,10-dioxooxacyclotetradecanyl]oxy]-4-methylcyclohexyl acetate | C33H59NO10 | 详情 | 详情 | |
| (XII) | 35368 | (1R,2R,4R,6S)-2-[[(3aR,4R,7R,8S,9S,10R,11R,13R,15R,15aR)-4-ethyl-8-hydroxy-11-methoxy-3a,7,9,11,13,15-hexamethyl-2,6,14-trioxododecahydro-4H-[1,3]dioxolo[4,5-c]oxacyclotetradecin-10-yl]oxy]-6-(dimethylamino)-4-methylcyclohexyl acetate | C34H57NO11 | 详情 | 详情 | |
| (XIII) | 35366 | 2-(2-pyridinyl)acetic acid | 16179-97-8 | C7H7NO2 | 详情 | 详情 |
| (XIV) | 35370 | (3R,4S,5R,6R,7R,9R,13S,14R)-6-[[(1R,2R,3S,5R)-2-(acetoxy)-3-(dimethylamino)-5-methylcyclohexyl]oxy]-14-ethyl-13-hydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,10-dioxooxa-11-cyclotetradecen-4-yl 2-(2-pyridinyl)acetate | C40H62N2O10 | 详情 | 详情 | |
| (XV) | 35371 | (2R,3S,7R,9R,10R,11R,12S,13R)-10-[[(1R,2R,3S,5R)-2-(acetoxy)-3-(dimethylamino)-5-methylcyclohexyl]oxy]-2-ethyl-9-methoxy-3,5,7,9,11,13-hexamethyl-6,14-dioxo-12-[[2-(2-pyridinyl)acetyl]oxy]oxa-4-cyclotetradecen-3-yl 1H-imidazole-1-carboxylate | C44H64N4O11 | 详情 | 详情 | |
| (XVI) | 35372 | C43H68N4O11 | 详情 | 详情 | ||
| (XVII) | 35373 | C53H75N5O11 | 详情 | 详情 |