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【结 构 式】 
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【分子编号】31943 【品名】Rifamycin S; (7S,11S,12R,13S,14R,15R,16R,17S,18S)-2,15,17-trihydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23,27,29-tetraoxo-8,30-dioxa-24-azatetracyclo[23.3.1.1(4,7).0(5,28)]triaconta-1(28),2,4,9,19,21,25-heptaen-13-yl acetate 【CA登记号】 |
【 分 子 式 】C37H45NO12 【 分 子 量 】695.76384 【元素组成】C 63.87% H 6.52% N 2.01% O 27.59% |
合成路线1
该中间体在本合成路线中的序号：(I)The reaction of rifamycin S (I) with pyridine perbromide (II) in 2-propanol/chloroform (70/30) mixture at 0 C gives 3-bromorifamicin S (III), which is then condensed with 2-amino-4-methyl-pyridine (IV) at 10 C. The o-quinoniminic compound (V) is then obtained. This compound is finally reduced with ascorbic acid.
| 【1】 US 262123 . |
| 【2】 de Angelis, L.; L-105. Drugs Fut 1982, 7, 4, 260. |
| 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) | 31943 | Rifamycin S; (7S,11S,12R,13S,14R,15R,16R,17S,18S)-2,15,17-trihydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23,27,29-tetraoxo-8,30-dioxa-24-azatetracyclo[23.3.1.1(4,7).0(5,28)]triaconta-1(28),2,4,9,19,21,25-heptaen-13-yl acetate | C37H45NO12 | 详情 | 详情 | |
| (III) | 31944 | (7S,11S,12R,13S,14R,15R,16R,17S,18S)-26-bromo-2,15,17-trihydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23,27,29-tetraoxo-8,30-dioxa-24-azatetracyclo[23.3.1.1(4,7).0(5,28)]triaconta-1(28),2,4,9,19,21,25-heptaen-13-yl acetate; 3-bromorifamicin S | C37H44BrNO12 | 详情 | 详情 | |
| (IV) | 14614 | 2-Amino-4-picoline; 4-Methyl-2-pyridinamine; 4-Methyl-2-pyridinylamine; 2-Amino-4-methylpyridine | 695-34-1 | C6H8N2 | 详情 | 详情 |
| (V) | 31945 | (7S,11S,12R,13S,14R,15R,16R,17S,18S)-2,15,17-trihydroxy-11-methoxy-3,7,12,14,16,18,22,30-octamethyl-6,23,36-trioxo-8,37-dioxa-24,27,33-triazahexacyclo[23.10.1.1(4,7).0(5,35).0(26,34).0(27,32)]heptatriaconta-1(35),2,4,9,19,21,24,26(34),28,30,32-undec | C43H49N3O11 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)This compound has been obtained by two related ways: 1. By direct condensation of rifamycin S (I) with 1-(2,4,6-trimethylphenyl)piperazine (II), followed by reduction of the quinone subunit to the target hydroquinone with sodium ascorbate. 2. The bromination of rifamycin S (I) with Br2/pyridine in DMF gives 3-bromorifamycin S (III), which is condensed with piperazine (II) and reduced to the target hydroquinone as before.
| 【1】 Vischer, W.; Traxler, P.; Kump, W.; Costa-Pereira, R.; Gowrishankar, R.; Zak, O.; Lydon, N.; Ashtekar, D.R.; Batt, E.; Tosch, W.; 3-Alkylbenzylpiperazinyl-rifamycins: New rifamycins with long plasma half-lives, high activity aganist Micobacterium avium complex (MAC) and reverse transcription. 27th Intersci Conf Antimicrob Agents Chemother 1987, Abst 275. |
| 【2】 (Novartis AG); Process for the preparation of a peptide derivative of the lysergic acid. CH 282603 . |
| 【3】 Traxler, P.; Vischer, W.; Zak, O.; New Rifamycins. Drugs Fut 1988, 13, 9, 845. |
| 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) | 31943 | Rifamycin S; (7S,11S,12R,13S,14R,15R,16R,17S,18S)-2,15,17-trihydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23,27,29-tetraoxo-8,30-dioxa-24-azatetracyclo[23.3.1.1(4,7).0(5,28)]triaconta-1(28),2,4,9,19,21,25-heptaen-13-yl acetate | C37H45NO12 | 详情 | 详情 | |
| (II) | 43687 | 1-(mesitylmethyl)piperazine | C14H22N2 | 详情 | 详情 | |
| (III) | 31944 | (7S,11S,12R,13S,14R,15R,16R,17S,18S)-26-bromo-2,15,17-trihydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23,27,29-tetraoxo-8,30-dioxa-24-azatetracyclo[23.3.1.1(4,7).0(5,28)]triaconta-1(28),2,4,9,19,21,25-heptaen-13-yl acetate; 3-bromorifamicin S | C37H44BrNO12 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(III)The mono-silylation of 2-aminoresorcinol (I) by means of tert-butyldimethylsilyl chloride and triethylamine yields silyl ether (II). Condensation of rifamycin S (III) with aminophenol (II), followed by oxidative treatment with MnO2 produces the benzoxazinorifamycin derivative (IV). Addition of N-propyl piperazine (V) to (IV) in the presence of MnO2 leads to the target piperazinyl benzoxazinorifamycin.
| 【1】 Yamashita, K.; Yamane, T.; Sakashita, S.; Hosoe, K.; Fujii, K. (Kaneka Corp.); Remedy for diseases caused by infection with Helicobacter. EP 0787494; EP 0861660; JP 1998298080; US 5981522; WO 9709047 . |
| 【2】 Yamane, T.; et al.; Synthesis and biological activity of 3'-hydroxy-5'-aminobenzoxazinorifamycin derivatives. Chem Pharm Bull 1993, 41, 1, 148. |
| 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) | 58101 | 2-amino-1,3-benzenediol | C6H7NO2 | 详情 | 详情 | |
| (II) | 58102 | 2-amino-3-{[tert-butyl(dimethyl)silyl]oxy}phenol | C12H21NO2Si | 详情 | 详情 | |
| (III) | 31943 | Rifamycin S; (7S,11S,12R,13S,14R,15R,16R,17S,18S)-2,15,17-trihydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23,27,29-tetraoxo-8,30-dioxa-24-azatetracyclo[23.3.1.1(4,7).0(5,28)]triaconta-1(28),2,4,9,19,21,25-heptaen-13-yl acetate | C37H45NO12 | 详情 | 详情 | |
| (IV) | 58103 | (7S,11S,12R,13S,14R,15R,16R,17S,18S)-32-{[tert-butyl(dimethyl)silyl]oxy}-2,15,17-trihydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23,37-trioxo-8,27,38-trioxa-24,34-diazahexacyclo[23.11.1.1~4,7~.0~5,36~.0~26,35~.0~28,33~]octatriaconta-1(36),2,4 | C49H62N2O13Si | 详情 | 详情 | |
| (V) | 58104 | 1-propylpiperazine | C7H16N2 | 详情 | 详情 |