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【结 构 式】 
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【药物名称】FR-900409, FK-409 【化学名称】4-Ethyl-2-[(Z)-hydroxyimino]-5-nitro-3(E)-hexenamide 【CA登记号】92454-60-9, 92454-83-6 (non-specified isomerism) 【 分 子 式 】C8H13N3O4 【 分 子 量 】215.21051 |
【开发单位】Fujisawa (Originator) 【药理作用】Angina pectoris, Treatment of, Antiplatelet Therapy, CARDIOVASCULAR DRUGS, Coagulation Disorders Therapy, HEMATOLOGIC DRUGS, Hypertension, Treatment of, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, Vasodilators, Nitric Oxide Donors |
合成路线1
The Wittig condensation of 2-ethyl-2(E)-butenal (I) with triethyl phosphonoacetate (II) by means of NaH in benzene gives (2E,4E)-4-ethyl-2,4-hexadienoic acid ethyl ester (III), which is hydrolyzed with NaOH to the corresponding free acid (IV). The reaction of (IV) with ethyl chloroformate and then with ammonia affords the (2E,4E)-2-ethyl-2,4-hexadienamide (V), which is finally treated with NaNO2 in methanol adjusted at pH 3.0 with cond. HCl.
| 【1】 Okamoto, M.; Iwami, M.; Takase, S.; Uchida, I.; Umehara, K.; Kohsaka, M.; Imanaka, H. (Fujisawa Pharmaceutical Co., Ltd.); New nitro aliphatic cpds., process for preparation thereof and use thereof. EP 0113106; JP 1990160750 . |
| 【2】 Aoki, H.; Imanaka, H.; Takase, S.; Okamoto, M.; Itoh, Y.; Hino, M.; Uchida, I.; Kohsaka, M.; FK409, a novel vasodilator isolated from the acid-treated fermentation broth of Streptomyces griseosporeus. III. Reaction mechanism and synthesis. J Antibiot 1989, 42, 44, 1589. |
| 【3】 Hino, M.; Hosoda, J.; Iwami, M.; Yoshida, K.; Okamoto, M.; Kohsaka, M.; Imanaka, H.; Okuhara, M.; Haruta, H.; Aoki, H.; FK409, a novel vasodilator isolated from the acid-treated fermentation broth of Streptomyces griseosporeus. I. Taxonomy, fermentation, isolation, and physico-chemical and biological characteristics. J Antibiot 1989, 42, 11, 1578. |
| 【4】 Hino, M.; Kohsaka, M.; Uchida, I.; Hashimoto, M.; Takase, S.; Okamoto, M.; Itoh, Y.; Structure and synthesis of FK409, a novel vasodilator isolated from Streptomyces as a semi-artificial fermentation product. Chem Pharm Bull 1989, 37, 10, 2864. |
| 【5】 Prous, J.; Castaner, J.; FK-409. Drugs Fut 1993, 18, 1, 9. |
| 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) | 13404 | (E)-2-Ethyl-2-butenal | 19780-25-7 | C6H10O | 详情 | 详情 |
| (II) | 10019 | Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate | 867-13-0 | C8H17O5P | 详情 | 详情 |
| (III) | 13406 | ethyl (2E,4E)-4-ethyl-2,4-hexadienoate | C10H16O2 | 详情 | 详情 | |
| (IV) | 13407 | (2E,4E)-4-Ethyl-2,4-hexadienoic acid | C8H12O2 | 详情 | 详情 | |
| (V) | 13408 | (2E,4E)-4-Ethyl-2,4-hexadienamide | C8H13NO | 详情 | 详情 |