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【结 构 式】 
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【分子编号】30160 【品名】1-(2-amino-2-oxoethyl)-4-(2-[2-[((4S,5R,6S)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-7-oxo-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-3-yl)methyl]-1,1-dioxo-1,2-dihydro-2H-naphtho[1,8-cd]isothiazol-6-yl]ethyl)-1,4-diazonia 【CA登记号】 |
【 分 子 式 】C46H58F6N6O15S3Si 【 分 子 量 】1173.2718792 【元素组成】C 47.09% H 4.98% F 9.72% N 7.16% O 20.45% S 8.2% Si 2.39% |
合成路线1
该中间体在本合成路线中的序号：(IL)Coupling of carbapenem (XLII) with sultam (VIIIb) under Mitsunobu conditions gave adduct (XLVII), which was desylilated to yield alcohol (XLVIII). Formation of the corresponding triflate, followed by condensation with bicyclic compound (XLV) provided (II), which was converted to (L) upon treatment with HCl and NaCl. The p-nitrobenzyl ester of (L) was finally deprotected by hydrogenation over Pd/C to provide the title carboxylic acid. A further procedure to obtain the target compound is to repeat the described synthesis but using carbapenem (XXXVII), instead of carbapenem (XLII).
| 【1】 Yasuda, N.; et al.; Preparation of anti-MRS carbapenem L-786,392. 38th Intersci Conf Antimicrob Agents Chemother (Sept 24 1998, San Diego) 1998, Abst F-31. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIIIb) | 30125 | 6-[2-[(triethylsilyl)oxy]ethyl]-2H-naphtho[1,8-cd]isothiazole-1,1(2H)-dione | C18H25NO3SSi | 详情 | 详情 | |
| (IL) | 30160 | 1-(2-amino-2-oxoethyl)-4-(2-[2-[((4S,5R,6S)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-7-oxo-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-3-yl)methyl]-1,1-dioxo-1,2-dihydro-2H-naphtho[1,8-cd]isothiazol-6-yl]ethyl)-1,4-diazonia | C46H58F6N6O15S3Si | 详情 | 详情 | |
| (XLII) | 30154 | (4S,5R,6S)-3-(hydroxymethyl)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-7-one | C24H34N2O7Si | 详情 | 详情 | |
| (XLV) | 30156 | 1-(2-amino-2-oxoethyl)-4-aza-1-azoniabicyclo[2.2.2]octane trifluoromethanesulfonate | C9H16F3N3O4S | 详情 | 详情 | |
| (XLVII) | 30158 | 2-[((4S,5R,6S)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-7-oxo-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-3-yl)methyl]-6-[2-[(triethylsilyl)oxy]ethyl]-2H-naphtho[1,8-cd]isothiazole-1,1(2H)-dione | C42H57N3O9SSi2 | 详情 | 详情 | |
| (XLVIII) | 30159 | 6-(2-hydroxyethyl)-2-[((4S,5R,6S)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-7-oxo-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-3-yl)methyl]-2H-naphtho[1,8-cd]isothiazole-1,1(2H)-dione | C36H43N3O9SSi | 详情 | 详情 | |
| (L) | 30161 | 1-(2-amino-2-oxoethyl)-4-[2-[2-([(4S,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]methyl)-1,1-dioxo-1,2-dihydro-2H-naphtho[1,8-cd]isothiazol-6-yl]ethyl]-1,4-diazoniabicyclo[2.2.2 | C39H44ClF3N6O12S2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)Several improvements is the synthesis of 258849 have been developed: The reaction of stannatrane chloride (I) with Et2Zn and CH2I2 in HF gives iodomethylstannatrane (II), which is condensed with the naphthosultam (III) (intermediate (VII) in previous synthesis of 258849, scheme 25884901a) by means of K2CO3 in DMF yielding the stannatrane derivative (IV). The reaction of (IV) with Tf2O and lutidine in dichloromethane affords the corresponding ester (V), which is condensed with 1-(carbamoylmethyl)-4-aza-1-azoniabicyclo[2.2.2]octane trifluoromethanesulfonate (VI) (intermediate (XLV) in scheme 25884901g) giving the stannatrane derivative (VII). The condensation of intermediate (VII) with carbapenem triflate (VIII) (intermediate (XLI) in scheme 25884901f) by means of a Pd catalyst in acetonitrile provides the protected carbapenem derivative (IX) (intermediate (II) in scheme 25884902a). Finally, this compound is deprotected first with HCl to eliminate the silyl group and then with H2 over Pd/C to eliminate the p-nitrobenzyl group.
| 【1】 Jensen, M.S.; et al.; Synthesis of an anti-methicillin-resistant Staphylococcus aureus (MRSA) carbapenem via stannatrane-mediated Stille coupling. Org Lett 2000, 2, 8, 1081. |
| 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) | 36871 | 5-chloro-1-aza-5-stannabicyclo[3.3.3]undecane | C9H18ClNSn | 详情 | 详情 | |
| (II) | 36872 | 5-(iodomethyl)-1-aza-5-stannabicyclo[3.3.3]undecane | C10H20INSn | 详情 | 详情 | |
| (III) | 30123 | 6-(2-hydroxyethyl)-2H-naphtho[1,8-cd]isothiazole-1,1(2H)-dione | C12H11NO3S | 详情 | 详情 | |
| (IV) | 36873 | 2-(1-aza-5-stannabicyclo[3.3.3]undec-5-ylmethyl)-6-(2-hydroxyethyl)-2H-naphtho[1,8-cd]isothiazole-1,1(2H)-dione | C22H30N2O3SSn | 详情 | 详情 | |
| (V) | 36874 | 2-[2-(1-aza-5-stannabicyclo[3.3.3]undec-5-ylmethyl)-1,1-dioxo-1,2-dihydro-2H-naphtho[1,8-cd]isothiazol-6-yl]ethyl trifluoromethanesulfonate | C23H29F3N2O5S2Sn | 详情 | 详情 | |
| (VI) | 30156 | 1-(2-amino-2-oxoethyl)-4-aza-1-azoniabicyclo[2.2.2]octane trifluoromethanesulfonate | C9H16F3N3O4S | 详情 | 详情 | |
| (VII) | 36875 | 1-(2-amino-2-oxoethyl)-4-[2-[2-(1-aza-5-stannabicyclo[3.3.3]undec-5-ylmethyl)-1,1-dioxo-1,2-dihydro-2H-naphtho[1,8-cd]isothiazol-6-yl]ethyl]-1,4-diazoniabicyclo[2.2.2]octane | C30H45N5O3SSn | 详情 | 详情 | |
| (VIII) | 30153 | (4R,5R,6S)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-7-oxo-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-3-yl trifluoromethanesulfonate | C24H31F3N2O9SSi | 详情 | 详情 | |
| (IX) | 30160 | 1-(2-amino-2-oxoethyl)-4-(2-[2-[((4S,5R,6S)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-7-oxo-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-3-yl)methyl]-1,1-dioxo-1,2-dihydro-2H-naphtho[1,8-cd]isothiazol-6-yl]ethyl)-1,4-diazonia | C46H58F6N6O15S3Si | 详情 | 详情 |