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【结 构 式】 
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【药物名称】KF-22678 【化学名称】[alpha(R),2R,7Z,9E,12R,13E,17R(R),20S]-alpha-Hydroxy-alpha,2,14-trimethyl-11,19-dioxo-12-[tetrahydropyran-2(R)-yloxy]-4,20-dithia-1,21-diazatricyclo[15.2.1.1(3,6)]heneicosa-3(21),5,7,9,13-pentanene-17-ethanetioic acid 20-oxide S-(5-methyl-2-oxo-1,3-dioxol-4-ylmethyl) ester 【CA登记号】186643-40-3 【 分 子 式 】C32H38N2O10S3 【 分 子 量 】706.85906 |
【开发单位】Kyowa Hakko (Originator) 【药理作用】Antibiotics and Alkaloids, Antineoplastic Antibiotics, ONCOLYTIC DRUGS |
合成路线1
Rearrangement of leinamycin (I) to thioester (III) was achieved by treatment with 4-chloromethyl-5-methyl-2-oxo-1,3-dioxolene (II) in the presence of KI and K2CO3. The required tetrahydropyranyl ether was then obtained by condensation of (III) with dihydropyran (IV) employing camphorsulfonic acid as the catalyst.
| 【1】 Kanda, Y.; Kono, M.; Kakita, S.; Takahashi, Y.; Yoshida, M.; Saitoh, Y.; Okabe, M.; Ashizawa, T.; Synthesis and antitumor activity of novel thioester derivatives of leinamycin. J Med Chem 1999, 42, 8, 1330. |
| 【2】 Kanda, Y.; Saitoh, Y.; Saito, H.; Ashizawa, T.; Sugiyama, K.; Gomi, K.; Kakita, S.; Takahashi, Y.; Murakata, C. (Kyowa Hakko Kogyo Co., Ltd.); DC107 derivs.. EP 0786462; US 5733924; WO 9700260 . |
| 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) | 40748 | C22H26N2O6S3 | 详情 | 详情 | ||
| (II) | 16911 | 4-(chloromethyl)-5-methyl-1,3-dioxol-2-one | C5H5ClO3 | 详情 | 详情 | |
| (III) | 40749 | (2R,12R,17R)-12-hydroxy-17-((1R)-1-hydroxy-1-methyl-2-[[(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl]sulfanyl]-2-oxoethyl)-2,14-dimethyl-11,19-dioxo-4-thia-20-thionia-1,21-diazatricyclo[15.2.1.1(3,6)]henicosa-3(21),5,7,9,13-pentaen-20-olate | C27H30N2O9S3 | 详情 | 详情 | |
| (IV) | 13684 | 3,4-Dihydro-2H-pyran;2,3-Dihydro-4H-pyran; 5,6-Dihydro-4H-pyran;Dihydropyran | 110-87-2 | C5H8O | 详情 | 详情 |