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【结 构 式】 
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【分子编号】33091 【品名】(2S,3R,7R,8R,11R,12R,13R,14R,15R,19R)-14-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-ethyl-12-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-2,7,11,13,15,19-hexamethyl-4,6,9,16,18-pentaoxatricyclo[13.3.2.0(3,7)]icosane-5,10,17-trione; (2S,3R,7R,8R,11R,12R,13R,14R,15R,19R)-14-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-ethyl-12-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-2,7,11,13,15,19-hexamethyl-4,6,9,16,18-pentaoxatricyclo[13.3.2.0(3,7)]icosane-5,10,17-trione 【CA登记号】 |
【 分 子 式 】C39H65NO15 【 分 子 量 】787.94284 【元素组成】C 59.45% H 8.31% N 1.78% O 30.46% |
合成路线1
该中间体在本合成路线中的序号：(VI)The intermediate dicyclic carbonate (VI) was prepared by two alternative procedures: Erythromycin A (I) was converted into 11,12-cyclic carbonate (II) upon treatment with ethylene carbonate (II). Reduction of (II) with NaBH4 afforded the 9-dihydroerythromicyn derivative (III), which was protected at the 2'-hydroxyl group of the cladinose moiety by acetylation with Ac2O in acetone. Conversion of the resulting acetylated compound (V) to the corresponding 6,9;11,12-dicyclic carbonate was achieved by reaction with either diphosgene or triphosgene in the presence of pyridine, and the subsequent hydrolysis of the 2'-acetate in MeOH at room temperature furnished intermediate (VI). In a shorter procedure, 2'-O-acetyl-9-dihydroerythromycin A (VII) was reacted with 1,1'-carbonyldiimidazole and NaH to give the corresponding dicyclic carbonate. The acetate ester was then hydrolyzed to (VI) by treatment with MeOH.
| 【1】 Morimoto, S.; Sugiyama, H.; Tanikawa, T.; Kashimura, M.; Asaka, T.; Suzuki, K.; Adachi, T.; Akashi, T.; Synthesis and antibacterial activitis of unique acyclides: 3-O-Acyl-5-O-desosaminylerythronolide 6,9;11,12-dicarbonates. 39th Intersci Conf Antimicrob Agents Chemother (Sept 26 1999, San Francisco) 1999, Abst F2160. |
| 【2】 Asaka, T.; Tanikawa, T.; Ishii, T.; Kashimura, M. (Taisho Pharmaceutical Co., Ltd.); Erythromycin A derivs.. WO 9813373 . |
| 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) | 33087 | (3R,4R,5R,6R,7R,9R,11R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-14-ethyl-7,12,13-trihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3,5,7,9,11,13-hexamethyl-2,10-oxacyclotetradecanedione; Erythromycin A | 114-07-8 | C37H67NO13 | 详情 | 详情 |
| (II) | 32802 | 1,3-dioxolan-2-one | 96-49-1 | C3H4O3 | 详情 | 详情 |
| (III) | 33088 | (3aR,4R,7R,8R,9R,10R,11R,13R,15R,15aR)-10-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-4-ethyl-11-hydroxy-8-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3a,7,9,11,13,15-hexamethyloctahydro-4H-[1,3]dioxolo[4,5-c]oxacyclotetradecine-2,6,14(3aH,7H)-trione; (3aR,4R,7R,8R,9R,10R,11R,13R,15R,15aR)-10-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-4-ethyl-11-hydroxy-8-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3a,7,9,11,13,15-hexamethyloctahydro-4H-[1,3]dioxolo[4,5-c]oxacyclotetradecine-2,6,14(3aH,7H)-trione | C38H65NO14 | 详情 | 详情 | |
| (IV) | 33089 | (3aR,4R,7R,8R,9R,10R,11R,13R,15S,15aR)-10-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-4-ethyl-11,14-dihydroxy-8-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3a,7,9,11,13,15-hexamethyldecahydro-4H-[1,3]dioxolo[4,5-c]oxacyclotetradecine-2,6(3aH)-dione; (3aR,4R,7R,8R,9R,10R,11R,13R,15S,15aR)-10-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-4-ethyl-11,14-dihydroxy-8-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3a,7,9,11,13,15-hexamethyldecahydro-4H-[1,3]dioxolo[4,5-c]oxacyclotetradecine-2,6(3aH)-dione | C38H67NO14 | 详情 | 详情 | |
| (V) | 33090 | (2S,3R,4S,6R)-2-[((3aR,4R,7R,8R,9R,10R,11R,13R,15S,15aR)-4-ethyl-11,14-dihydroxy-8-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3a,7,9,11,13,15-hexamethyl-2,6-dioxododecahydro-4H-[1,3]dioxolo[4,5-c]oxacyclotetradecin-10-yl)oxy]-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl acetate; (2S,3R,4S,6R)-2-[((3aR,4R,7R,8R,9R,10R,11R,13R,15S,15aR)-4-ethyl-11,14-dihydroxy-8-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3a,7,9,11,13,15-hexamethyl-2,6-dioxododecahydro-4H-[1,3]dioxolo[4,5-c]oxacyclotetradecin-10-yl)oxy]-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl acetate | C40H69NO15 | 详情 | 详情 | |
| (VI) | 33091 | (2S,3R,7R,8R,11R,12R,13R,14R,15R,19R)-14-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-ethyl-12-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-2,7,11,13,15,19-hexamethyl-4,6,9,16,18-pentaoxatricyclo[13.3.2.0(3,7)]icosane-5,10,17-trione; (2S,3R,7R,8R,11R,12R,13R,14R,15R,19R)-14-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-ethyl-12-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-2,7,11,13,15,19-hexamethyl-4,6,9,16,18-pentaoxatricyclo[13.3.2.0(3,7)]icosane-5,10,17-trione | C39H65NO15 | 详情 | 详情 | |
| (VII) | 33092 | (2S,3R,4S,6R)-4-(dimethylamino)-2-[((3R,4R,5R,6R,7R,9R,11S,12R,13S,14R)-14-ethyl-7,10,12,13-tetrahydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3,5,7,9,11,13-hexamethyl-2-oxooxacyclotetradecanyl)oxy]-6-methyltetrahydro-2H-pyran-3-yl acetate; (2S,3R,4S,6R)-4-(dimethylamino)-2-[((3R,4R,5R,6R,7R,9R,11S,12R,13S,14R)-14-ethyl-7,10,12,13-tetrahydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3,5,7,9,11,13-hexamethyl-2-oxooxacyclotetradecanyl)oxy]-6-methyltetrahydro-2H-pyran-3-yl acetate | C39H71NO14 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)Removal of the desosamine unit was effected by hydrolysis in 1N HCl at r.t. The resulting diol (VIII) was then selectively acetylated at the 2'-hydroxyl yielding monoacetate ester (IX). Further coupling of (IX) with 3-pyridylacetic acid-HCl (X) was carried out by means of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) or, alternatively, by previous activation of (X) as the mixed anhydride with pivalic acid to furnish the 3-O-pyridylacetyl ester (XI). The protecting acetate group of (XI) was finally removed by selective hydrolysis in boiling MeOH.
| 【1】 Morimoto, S.; Sugiyama, H.; Tanikawa, T.; Kashimura, M.; Asaka, T.; Suzuki, K.; Adachi, T.; Akashi, T.; Synthesis and antibacterial activitis of unique acyclides: 3-O-Acyl-5-O-desosaminylerythronolide 6,9;11,12-dicarbonates. 39th Intersci Conf Antimicrob Agents Chemother (Sept 26 1999, San Francisco) 1999, Abst F2160. |
| 【2】 Asaka, T.; Tanikawa, T.; Ishii, T.; Kashimura, M. (Taisho Pharmaceutical Co., Ltd.); Erythromycin A derivs.. WO 9813373 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 33091 | (2S,3R,7R,8R,11R,12R,13R,14R,15R,19R)-14-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-ethyl-12-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-2,7,11,13,15,19-hexamethyl-4,6,9,16,18-pentaoxatricyclo[13.3.2.0(3,7)]icosane-5,10,17-trione; (2S,3R,7R,8R,11R,12R,13R,14R,15R,19R)-14-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-ethyl-12-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-2,7,11,13,15,19-hexamethyl-4,6,9,16,18-pentaoxatricyclo[13.3.2.0(3,7)]icosane-5,10,17-trione | C39H65NO15 | 详情 | 详情 | |
| (VIII) | 33093 | (2S,3R,7R,8R,11R,12S,13S,14R,15R,19R)-14-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-ethyl-12-hydroxy-2,7,11,13,15,19-hexamethyl-4,6,9,16,18-pentaoxatricyclo[13.3.2.0(3,7)]icosane-5,10,17-trione | C31H51NO12 | 详情 | 详情 | |
| (IX) | 33094 | (2S,3R,4S,6R)-4-(dimethylamino)-2-[[(2S,3R,7R,8R,11R,12S,13S,14R,15R,19R)-8-ethyl-12-hydroxy-2,7,11,13,15,19-hexamethyl-5,10,17-trioxo-4,6,9,16,18-pentaoxatricyclo[13.3.2.0(3,7)]icos-14-yl]oxy]-6-methyltetrahydro-2H-pyran-3-yl acetate | C33H53NO13 | 详情 | 详情 | |
| (X) | 16168 | 2-(3-pyridinyl)acetic acid; 3-Pyridylacetic acid | 501-81-5 | C7H7NO2 | 详情 | 详情 |
| (XI) | 33095 | (2S,3R,7R,8R,11R,12S,13R,14R,15R,19R)-14-[[(2S,3R,4S,6R)-3-(acetoxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-ethyl-2,7,11,13,15,19-hexamethyl-5,10,17-trioxo-4,6,9,16,18-pentaoxatricyclo[13.3.2.0(3,7)]icos-12-yl 2-(3-pyridinyl)acetate; (2S,3R,7R,8R,11R,12S,13R,14R,15R,19R)-14-[[(2S,3R,4S,6R)-3-(acetoxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-ethyl-2,7,11,13,15,19-hexamethyl-5,10,17-trioxo-4,6,9,16,18-pentaoxatricyclo[13.3.2.0(3,7)]icos-12-yl 2-(3-pyridinyl)acetate | C40H58N2O14 | 详情 | 详情 |