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【结 构 式】 
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【分子编号】13713 【品名】2-Chloroacetyl isocyanate 【CA登记号】4461-30-7 |
【 分 子 式 】C3H2ClNO2 【 分 子 量 】119.50712 【元素组成】C 30.15% H 1.69% Cl 29.67% N 11.72% O 26.78% |
合成路线1
该中间体在本合成路线中的序号：(XVII)L-threonic acid (XI), which is readily available from L-ascorbic acid (IX), is converted to L-N-benzyloxycarbonyl-4-hydroxyallothreoninamide (VIII). This in turn is transformed to (3S,4S)-cis-3-amino-4-carbamoyloxymethyl-2-azetidinone-1-sulfonic acid (XVIII). Condensation of the azetidinone (XVIII) with the activated aminothiazole portion (XIX) followed by a necessary deprotection step affords the monocyclic beta-lactam. Dissolution of the beta-lactam in aqueous sodium acetate yields the disodium salt, carumonam. Other routes of synthesis have been discussed.
| 【1】 Weigele, M.; Wei, C.; Tengi, J.; Ro-172301 (AMA-1080), a new monocyclic beta-lactam antibiotic: Stereorational synthesis. Intersci Conf Antimicrob Agents Chemother 1983, Abst 324. |
| 【2】 Hachiguchi, S.; Ochiai, M.; Kishimoto, S.; Matsuo, T.; Kondo, M.; Sendai, M.; Tomimoto, M.; Chemical modification of sulfazecin: Synthesis of 4-(substituted methyl)-2-azetidinone-1-sulfonic acid derivatives. J Antibiot 1985, 38, 3, 346-371. |
| 【3】 Christenson, J.; Squires, E.; Carumonam Sodium. Drugs Fut 1985, 10, 12, 967. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 28759 | benzyl (1S,2R)-1-(aminocarbonyl)-2,3-dihydroxypropylcarbamate | C12H16N2O5 | 详情 | 详情 | |
| (IX) | 29820 | (5R)-5-[(1S)-1,2-dihydroxyethyl]-3,4-dihydroxy-2(5H)-furanone | 50-81-7 | C6H8O6 | 详情 | 详情 |
| (X) | 10722 | 1-Methoxy-1-methylethyl methyl ether; 2,2-Dimethoxypropane | 77-76-9 | C5H12O2 | 详情 | 详情 |
| (XI) | 29821 | calcium di[(2R)-2-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-hydroxyethanoate] | C14H22CaO10 | 详情 | 详情 | |
| (XII) | 29822 | (2R)-2-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-hydroxyethanamide | C7H13NO4 | 详情 | 详情 | |
| (XIII) | 29823 | (2S)-2-azido-2-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethanamide | C7H12N4O3 | 详情 | 详情 | |
| (XIV) | 29824 | benzyl (1S)-2-amino-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-oxoethylcarbamate | C15H20N2O5 | 详情 | 详情 | |
| (XV) | 29825 | (2R,3S)-4-amino-3-[[(benzyloxy)carbonyl]amino]-2-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-4-oxobutyl 2-chloroacetate | C17H23ClN2O6S | 详情 | 详情 | |
| (XVI) | 29826 | N,N,N-tributyl-1-butanaminium (2S,3S)-3-[[(benzyloxy)carbonyl]amino]-2-(hydroxymethyl)-4-oxo-1-azetidinesulfonate | C28H49N3O7S | 详情 | 详情 | |
| (XVII) | 13713 | 2-Chloroacetyl isocyanate | 4461-30-7 | C3H2ClNO2 | 详情 | 详情 |
| (XVIII) | 29827 | (2S,3S)-2-[[(aminocarbonyl)oxy]methyl]-3-ammonio-4-oxo-1-azetidinesulfonate | C5H9N3O6S | 详情 | 详情 | |
| (XIX) | 29828 | tert-butyl 2-([[(Z)-1-(2-amino-1,3-thiazol-4-yl)-2-(1,3-benzothiazol-2-ylsulfanyl)-2-oxoethylidene]amino]oxy)acetate | C18H18N4O4S3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)By condensation of fumagillol [(3R,4S,5S,6R)-4-(1,2-epoxy-1,5-dimethyl4-hexenyl)-6-hydroxy-5-methoxy-1-oxaspiro[2.5]octane] (I) with chloroacetylisocyanate (II) by means of dimethylaminopyridine (DMAP) in dichloromethane.
| 【1】 Fujita, T.; Kanamaru, T.; Folkman, M.; Ingber, D. (Children's Med. Cent. Corp.; Takeda Chemical Industries, Ltd.); Angiogenesis inhibitory agent. EP 0357061 . |
| 【2】 Kishimoto, S.; Fujita, T. (Takeda Chemical Industries, Ltd.); Fumagillol derivs. EP 0359036; EP 0682020; JP 1991007270; US 5164410; US 5166172; US 5180738; US 5698586 . |
| 【3】 Kishimoto, S.; Marui, S.; Fujita, T. (Takeda Chemical Industries, Ltd.); Cyclohexanol derivs., production and use thereof. EP 0415294; JP 1991279376; US 5180735 . |
| 【4】 Marui, S.; Itoh, F.; Kozai, Y.; Sudo, K.; Kishimoto, S.; Chemical modification of fumagillin. I. 6-O-Acyl, 6-O-sulfonyl, 6-O-alkyl, and 6-O-(N-substituted-carbamoyl)fumagillols. Chem Pharm Bull 1992, 40, 1, 96-101. |
| 【5】 Mealy, N.; Prous, J.; Castaner, J.; AGM-1470. Drugs Fut 1994, 19, 11, 981. |