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【结 构 式】 
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【药物名称】RPR-132552 【化学名称】(3R,4R,5E,10E,12E,14S,16R,26aR)-16-Fluoro-14-hydroxy-3-isopropyl-4,12-dimethyl-3,4,8,9,14,15,16,17,24,25,26,26a-dodecahydro-7H-21,18-nitrilo-1H,22H-pyrrolo[2,1-c][1,8,4,19]dioxadiazacyclotetracosine-1,7,22-trione 【CA登记号】318498-76-9 【 分 子 式 】C28H38FN3O6 【 分 子 量 】531.62996 |
【开发单位】Aventis Pharma (Originator) 【药理作用】Antibiotics, ANTIINFECTIVE THERAPY, Streptogramins |
合成路线1
Reduction of the keto function of pristinamycine IIB (I) with NaBH4 in the presence of HOAc afforded diol (II). The 14-hydroxy group of (II) was then selectively protected as the tert-butyldiphenylsilyl ether, yielding (III). Subsequent fluorination of the 16-hydroxyl of (III) was achieved by treatment with diethylaminosulfur trifluoride. Finally, deprotection of the resultant silyl ether (IV) was effected by means of tetrabutylammonium fluoride in THF. A closely related method was based on the protection of (II) as the 14-O-tert-butyldimethylsilyl derivative (V). After fluorination of (V) with diethylaminosulfur trifluoride, the resultant fluoro silyl compound (VI) was deprotected with triethylamine trihydrofluoride.
| 【1】 Barriere, J.-C.; Achard, D.; Grisoni, S.; Bacque, E.; Ribeill, Y.; Bouquerel, J.; Desmazeau, P.; Leconte, J.-P.; Ronan, B. (Aventis Pharma SA); Streptogramin derivs., preparation and compsns. containing them. EP 1187847; FR 2795733; WO 0102427 . |
| 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) | 59395 | (7R,10R,11R,21S)-21-hydroxy-10-isopropyl-11,19-dimethyl-9,26-dioxa-3,15,28-triazatricyclo[23.2.1.0~3,7~]octacosa-1(27),12,17,19,25(28)-pentaene-2,8,14,23-tetrone | C28H37N3O7 | 详情 | 详情 | |
| (II) | 59396 | (7R,10R,11R,21S,23S)-21,23-dihydroxy-10-isopropyl-11,19-dimethyl-9,26-dioxa-3,15,28-triazatricyclo[23.2.1.0~3,7~]octacosa-1(27),12,17,19,25(28)-pentaene-2,8,14-trione | C28H39N3O7 | 详情 | 详情 | |
| (III) | 59397 | (7R,10R,11R,21S,23S)-21-{[tert-butyl(diphenyl)silyl]oxy}-23-hydroxy-10-isopropyl-11,19-dimethyl-9,26-dioxa-3,15,28-triazatricyclo[23.2.1.0~3,7~]octacosa-1(27),12,17,19,25(28)-pentaene-2,8,14-trione | C44H57N3O7Si | 详情 | 详情 | |
| (IV) | 59398 | (7R,10R,11R,21S,23R)-21-{[tert-butyl(diphenyl)silyl]oxy}-23-fluoro-10-isopropyl-11,19-dimethyl-9,26-dioxa-3,15,28-triazatricyclo[23.2.1.0~3,7~]octacosa-1(27),12,17,19,25(28)-pentaene-2,8,14-trione | C44H56FN3O6Si | 详情 | 详情 | |
| (V) | 59399 | (7R,10R,11R,21S,23S)-21-{[tert-butyl(dimethyl)silyl]oxy}-23-hydroxy-10-isopropyl-11,19-dimethyl-9,26-dioxa-3,15,28-triazatricyclo[23.2.1.0~3,7~]octacosa-1(27),12,17,19,25(28)-pentaene-2,8,14-trione | C34H53N3O7Si | 详情 | 详情 | |
| (VI) | 59400 | (7R,10R,11R,21S,23R)-21-{[tert-butyl(dimethyl)silyl]oxy}-23-fluoro-10-isopropyl-11,19-dimethyl-9,26-dioxa-3,15,28-triazatricyclo[23.2.1.0~3,7~]octacosa-1(27),12,17,19,25(28)-pentaene-2,8,14-trione | C34H52FN3O6Si | 详情 | 详情 |
合成路线2
In an alternative procedure, diol (II) was selectively protected as the 14-allyl ether (VIII) by O-alkylation with allyl bromide (VII) in the presence of K2CO3. Displacement of the 16-hydroxyl of (VIII) with diethylaminosulfur trifluoride provided fluoride (IX). The O-allyl protecting group of (IX) was finally removed employing p-toluenesulfonic acid and palladium tetrakis(triphenylphosphine).
| 【1】 Barriere, J.-C.; Achard, D.; Grisoni, S.; Bacque, E.; Ribeill, Y.; Bouquerel, J.; Desmazeau, P.; Leconte, J.-P.; Ronan, B. (Aventis Pharma SA); Streptogramin derivs., preparation and compsns. containing them. EP 1187847; FR 2795733; WO 0102427 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 59396 | (7R,10R,11R,21S,23S)-21,23-dihydroxy-10-isopropyl-11,19-dimethyl-9,26-dioxa-3,15,28-triazatricyclo[23.2.1.0~3,7~]octacosa-1(27),12,17,19,25(28)-pentaene-2,8,14-trione | C28H39N3O7 | 详情 | 详情 | |
| (VII) | 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
| (VIII) | 59397 | (7R,10R,11R,21S,23S)-21-{[tert-butyl(diphenyl)silyl]oxy}-23-hydroxy-10-isopropyl-11,19-dimethyl-9,26-dioxa-3,15,28-triazatricyclo[23.2.1.0~3,7~]octacosa-1(27),12,17,19,25(28)-pentaene-2,8,14-trione | C44H57N3O7Si | 详情 | 详情 | |
| (IX) | 59398 | (7R,10R,11R,21S,23R)-21-{[tert-butyl(diphenyl)silyl]oxy}-23-fluoro-10-isopropyl-11,19-dimethyl-9,26-dioxa-3,15,28-triazatricyclo[23.2.1.0~3,7~]octacosa-1(27),12,17,19,25(28)-pentaene-2,8,14-trione | C44H56FN3O6Si | 详情 | 详情 |