RPR-202868, -Drug Synthesis Database

【结构式】

【药物名称】RPR-202868

【化学名称】5-[(2S)-1,2,3,6-Tetrahydro-5-(4-morpholinylmethyl)-2-pyridinecarboxylic acid]pristinamycin IA
　　　　　　N-(3-Hydroxypyridin-2-ylcarbonyl)-L-threonyl-D-(2-aminobutyryl)-L-prolyl-L-N-methyl-[4-(N,N-dimethylamino)]phenylalanyl-L-[5-(morpholin-4-ylmethyl)-1,2,3,6-tetrahydropyridin-2(S)-ylcarbonyl]-2-phenyl-L-glycine C-1.6-O-3.1-lactone

【CA登记号】325965-23-9

【分子式】C₅₀H₆₃N₉O₁₀

【分子量】950.11391

【开发单位】Aventis Pharma (Originator)

【药理作用】Antibacterial Drugs, ANTIINFECTIVE THERAPY, Streptogramins

合成路线1 合成路线2

合成路线1

Reduction of the keto group of 5-delta-methylene pristinamycin IA (I) by means of NaBH4 in the presence of CeCl3 provided the allyl alcohol (II). Subsequent chlorination of (II) with SOCl2, furnished a mixture of compounds containing the 5-delta-(chloromethyl) (III) and the 5-gamma-chloro-5-delta-methylene (IV) derivatives. Treatment of the crude mixture with morpholine (V) in refluxing acetonitrile yielded the title 5-delta-morpholinomethyl analogue.

参考文献中间体

【1】 Barriere, J.C.; Bacque, E.; Puchault, G.; Dutruc-Rooset, G.; Doerflinger, G.; Berthaud, N.; Design and synthesis of RPR202868, the pristinamycin I component of RPR202868/RPR132552, a new oral streptogramin. 41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001, Chicago) 2001, Abst F-359.
【2】 Barriere, J.-C.; Pantel, G.; Bacqué, E.; Doerflinger, G.; Dutruc-Rosset, G. (Aventis Pharma SA); Streptogramin derivs., production thereof and compsns. containing the same. EP 1204675; FR 2796949; US 6541451; WO 0110895 .

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)	41288			C₄₆H₅₄N₈O₁₀	详情	详情
(II)	59348	N-{(6R,9S,10R,13S,15aS,22S,24aS)-22-[4-(dimethylamino)benzyl]-6-ethyl-17-hydroxy-10,23-dimethyl-18-methylene-5,8,12,15,21,24-hexaoxo-13-phenyldocosahydro-12H-pyrido[2,1-f]pyrrolo[2,1-l][1,4,7,10,13,16]oxapentaazacyclononadecin-9-yl}-3-hydroxy-2-pyridinecarboxamide		C₄₆H₅₆N₈O₁₀	详情	详情
(III)	59349	N-{(6R,9S,10R,13S,15aS,22S,24aS)-18-(chloromethyl)-22-[4-(dimethylamino)benzyl]-6-ethyl-10,23-dimethyl-5,8,12,15,21,24-hexaoxo-13-phenyl-1,2,3,5,6,7,8,9,10,13,14,15,15a,16,19,21,22,23,24,24a-icosahydro-12H-pyrido[2,1-f]pyrrolo[2,1-l][1,4,7,10,13,16]oxapentaazacyclononadecin-9-yl}-3-hydroxy-2-pyridinecarboxamide		C₄₆H₅₅ClN₈O₉	详情	详情
(IV)	59350	N-{(6R,9S,10R,13S,15aS,22S,24aS)-17-chloro-22-[4-(dimethylamino)benzyl]-6-ethyl-10,23-dimethyl-18-methylene-5,8,12,15,21,24-hexaoxo-13-phenyldocosahydro-12H-pyrido[2,1-f]pyrrolo[2,1-l][1,4,7,10,13,16]oxapentaazacyclononadecin-9-yl}-3-hydroxy-2-pyridinecarboxamide		C₄₆H₅₅ClN₈O₉	详情	详情
(V)	10388	Morpholine	110-91-8	C₄H₉NO	详情	详情

合成路线2

In an alternative method, Michael addition of morpholine (V) to the unsaturated ketone (I) gave adduct (VI). Subsequent ketone reduction in (VI) with NaBH4 provided the corresponding alcohol (VII) as a diastereomeric mixture. Dehydration of alcohol (VII), upon treatment with diethylaminosulfur trifluoride, then yielded the title compound.

参考文献中间体

【1】 Barriere, J.-C.; Pantel, G.; Bacqué, E.; Doerflinger, G.; Dutruc-Rosset, G. (Aventis Pharma SA); Streptogramin derivs., production thereof and compsns. containing the same. EP 1204675; FR 2796949; US 6541451; WO 0110895 .

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)	41288			C₄₆H₅₄N₈O₁₀	详情	详情
(V)	10388	Morpholine	110-91-8	C₄H₉NO	详情	详情
(VI)	59352	N-[(6R,9S,10R,13S,15aS,22S,24aS)-22-[4-(dimethylamino)benzyl]-6-ethyl-10,23-dimethyl-18-(4-morpholinylmethyl)-5,8,12,15,17,21,24-heptaoxo-13-phenyldocosahydro-12H-pyrido[2,1-f]pyrrolo[2,1-l][1,4,7,10,13,16]oxapentaazacyclononadecin-9-yl]-3-hydroxy-2-pyridinecarboxamide		C₅₀H₆₃N₉O₁₁	详情	详情
(VII)	59351	N-[(6R,9S,10R,13S,15aS,22S,24aS)-22-[4-(dimethylamino)benzyl]-6-ethyl-17-hydroxy-10,23-dimethyl-18-(4-morpholinylmethyl)-5,8,12,15,21,24-hexaoxo-13-phenyldocosahydro-12H-pyrido[2,1-f]pyrrolo[2,1-l][1,4,7,10,13,16]oxapentaazacyclononadecin-9-yl]-3-hydroxy-2-pyridinecarboxamide		C₅₀H₆₅N₉O₁₁	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)