5-Fluorodeoxyuridine, Doxifluridine, 5-DFUR, Ro-21-9738, Furtulon, -Drug Synthesis Database

【结构式】

【药物名称】5-Fluorodeoxyuridine, Doxifluridine, 5-DFUR, Ro-21-9738, Furtulon

【化学名称】5'-Deoxy-5-fluorouridine

【CA登记号】3094-09-5

【分子式】C₉H₁₁FN₂O₅

【分子量】246.19682

【开发单位】Chugai (Originator), Roche (Originator)

【药理作用】Oncolytic Drugs, Apoptosis Inducers, Pyrimidine Antagonists, Thymidylate Synthase Inhibitors

合成路线1 合成路线2

合成路线1

The condensation of bis(trimethylsilyl)fluorouracil (I) with 5-deoxy-1,2,3-tri-O-acetyl-D-ribofuranose (II) in the presence of trimethylsilyl trifluoromethanesulfonate (III) gives the fully protected compound (IV), which is finally deprotected by the usual methods.

参考文献中间体

【1】 D'Souza, R.; Arnold, W.; Van Koeveringe, J.A.; Kiss, J.; Stereospecific synthesis of the anticancer agent 5'-deoxy-5-fluorouridine (5-DFUR) and its 5'-deuterated derivatives. Helv Chim Acta 1982, 65, 5, 1522.

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)	30002	5-fluoro-1,3-bis(trimethylsilyl)-2,4(1H,3H)-pyrimidinedione		C₁₀H₁₉FN₂O₂Si₂	详情	详情
(II)	16748	(2R,3R,4R,5S)-4,5-bis(acetoxy)-2-methyltetrahydro-3-furanyl acetate	62211-93-2	C₁₁H₁₆O₇	详情	详情
(III)	30003	trifluoromethyl (trimethylsilyl)methyl sulfone; trimethyl[[(trifluoromethyl)sulfonyl]methyl]silane		C₅H₁₁F₃O₂SSi	详情	详情
(IV)	30004	(2R,3R,4R,5R)-4-(acetoxy)-2-[5-fluoro-2,4-dioxo-3-(trimethylsilyl)-3,4-dihydro-1(2H)-pyrimidinyl]-5-methyltetrahydro-3-furanyl acetate		C₁₆H₂₃FN₂O₇Si	详情	详情

合成路线2

This compound can be prepared by several different ways: 1) The reaction of 5-fluorouridine (I) with 2,2-dimethoxypropane (A) by means of p-toluenesulfonic acid gives 2',3'-isopropylidene-5-fluorouridine (III), which is treated with triphenylphosphite methiodide in DMF to afford 5'-deoxy-5'-iodo-2',3'-isopropylidene-5-fluorouridine (IV). The reduction of (IV) with H2 over Pd/C in methanol-triethyl-amine yields 5'-deoxy-2',3'-isopropylidene-5-fluorouridine (V), which is finally hydrolyzed with aqueous trifluoroacetic acid. 2) The hydrolysis of compound (IV) with aqueous trifluoroacetic acid as before gives 5'-deoxy-5'-iodouridine (II), which is finally reduced with H2 over Pd/C as before. 3) Compound (II) can also be obtained by reaction of (I) with triphenyl phosphite methiodide as before. 4) It can also be prepared via reduction of the 5'-chloro intermediate with tributyltin hydride.

参考文献中间体

【1】 Beranek, J.; Hrebabecky, H.; Analogs of nucleosides. XVI. 5'-Halo-2',3'-sulfites in the synthesis of 2',5'-dideoxy-5-fluorouridine and related analogs. Coll Czech Chem Commun 1978, 43, 15, 3268-78.
【2】 Cook, A.F.; et al.; Fluorinated pyrimidine nucleosides. 3. Synthesis and antitumor activity of a series of 5'-deoxy-5-fluoropyrimidine nucleosides. J Med Chem 1979, 22, 11, 1330-35.
【3】 Cook, A.F. (Hoffmann-La Roche, Inc.); 5'-Deoxy-5-fluoropyrimidine nucleosides. DE 2756653; ES 471584; FR 2374334; GB 1589688; JP 53095982; US 4071680 .
【4】 Castaner, J.; Albonico, S.M.; Serradell, M.N.; Blancafort, P.; Doxifluridine. Drugs Fut 1981, 6, 2, 80.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	10722	1-Methoxy-1-methylethyl methyl ether; 2,2-Dimethoxypropane	77-76-9	C₅H₁₂O₂	详情	详情
(I)	32205	1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-fluoro-2,4(1H,3H)-pyrimidinedione; 5-Fluorouridine	316-46-1	C₉H₁₁FN₂O₆	详情	详情
(II)	32206	1-[(2R,3R,4S,5S)-3,4-dihydroxy-5-(iodomethyl)tetrahydro-2-furanyl]-5-fluoro-2,4(1H,3H)-pyrimidinedione		C₉H₁₀FIN₂O₅	详情	详情
(III)	32207	2',3'-Isopropylidene-5-fluorouridine; 5-Fluoro-1-[(4R,6R)-6-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-2,4(1H,3H)-pyrimidinedione		C₁₂H₁₅FN₂O₆	详情	详情
(IV)	32208	5-Fluoro-1-[(4R,6S)-6-(iodomethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-2,4(1H,3H)-pyrimidinedione; 5'-Deoxy-5'-iodo-2',3'-isopropylidene-5-fluorouridine		C₁₂H₁₄FIN₂O₅	详情	详情
(V)	32209	5'-Deoxy-2',3'-isopropylidene-5-fluorouridine; 5-Fluoro-1-[(4R,6R)-2,2,6-trimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-2,4(1H,3H)-pyrimidinedione		C₁₂H₁₅FN₂O₅	详情	详情

Extended Information