L-beta-BV-OddU, BCH-2639, -Drug Synthesis Database

【结构式】

【药物名称】L-beta-BV-OddU, BCH-2639

【化学名称】5-[(E)-2-Bromovinyl]-1-[2(S)-(hydroxymethyl)-1,3-dioxolan-4(S)-yl]pyrimidine-2,4(1H,3H)-dione
　　　　　　5-[(E)-2-Bromovinyl)-1-[2(S)-(hydroxymethyl)-1,3-dioxolan-4(S)-yl]uracil

【CA登记号】161105-93-7

【分子式】C₁₀H₁₁BrN₂O₅

【分子量】319.11357

【开发单位】Shire BioChem (Originator), University of Georgia (Originator), Yale University (Originator)

【药理作用】ANTIINFECTIVE THERAPY, Anti-Varicella Zoster Virus Drugs, Antiviral Drugs

合成路线1 合成路线2

合成路线1

Hydrogenolysis of benzyl ether (I) in the presence of Pd/C afforded dioxolane alcohol (II), which was acetylated with Ac2O and pyridine to give diacetate (III). Subsequent condensation of (III) with the silylated (2-bromovinyl)uracil (IV) led to a diastereomeric mixture of nucleosides (V) and (VI). After chromatographic isolation of the desired isomer (V), hydrolysis of the acetate ester using K2CO3 in MeOH yielded the title compound.

参考文献中间体

【1】 Dixit, D.M.; Wang, W.; Yuen, L.; Jin, H.; Bednarski, K.; Evans, C.A.; Mansour, T.S.; Inhibitory activities of herpes simplex viruses type 1 and 2 and human cytomegalovirus by stereoisomers of 2'-deoxy-3'-oxa-5(E)-(bromovinyl)uridines and their 4'-thio analogues. Bioorg Med Chem Lett 1994, 4, 22, 2667.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	39263	(2S)-2-[(benzyloxy)methyl]-1,3-dioxolan-4-yl acetate	C₁₃H₁₆O₅	详情	详情
(II)	39264	(2S)-2-(hydroxymethyl)-1,3-dioxolan-4-yl acetate	C₆H₁₀O₅	详情	详情
(III)	39265	[(2S)-4-(acetoxy)-1,3-dioxolan-2-yl]methyl acetate	C₈H₁₂O₆	详情	详情
(IV)	39266	5-[(E)-2-bromoethenyl]-2,4-bis[(trimethylsilyl)oxy]pyrimidine; 5-[(E)-2-bromoethenyl]-2-[(trimethylsilyl)oxy]-4-pyrimidinyl trimethylsilyl ether	C₁₂H₂₁BrN₂O₂Si₂	详情	详情
(V)	39267	[(2S,4S)-4-[5-[(E)-2-bromoethenyl]-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-1,3-dioxolan-2-yl]methyl acetate	C₁₂H₁₃BrN₂O₆	详情	详情
(VI)	39268	[(2S,4R)-4-[5-[(E)-2-bromoethenyl]-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-1,3-dioxolan-2-yl]methyl acetate	C₁₂H₁₃BrN₂O₆	详情	详情

合成路线2

The condensation of the chiral dioxolane (I) with 5(E)-(2-bromovinyl)uracil (II) by means of Tbdms-OTf and lutidine gives the silylated nucleoside (II), which is purified by chromatography. Finally, this compound is deprotected by means of TBAF in acetonitrile. (1,2)

参考文献中间体

【1】 Gumina, G.; Li, L.; Lee, C.S.; Cheng, Y.-C.; Choi, Y.; Tsujii, E.; Grill, S.; Gullen, E.; Chu, C.K.; Structure-activity relationships of (E)-5-(2-bromovinyl)uracil and related pyrimidine nucleosides as antiviral agents for herpes viruses. J Med Chem 2000, 43, 13, 2538.
【2】 Chu, C.K.; Cheng, Y.-C.; Li, L.; Chai, Y. (University of Georgia; Yale University); 5-(E)-Bromovinyl uracil analogues and related pyrimidine nucleosides as anti-viral agents and methods of use. CA 2378370; EP 1204415; US 6653318; WO 0106986 .

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)	51553	(2R)-2-([[tert-butyl(dimethyl)silyl]oxy]methyl)-1,3-dioxolan-4-yl acetate		C₁₂H₂₄O₅Si	详情	详情
(II)	38073	5-[(E)-2-bromoethenyl]-2,4(1H,3H)-pyrimidinedione	69304-49-0	C₆H₅BrN₂O₂	详情	详情
(III)	51554	5-[(E)-2-bromoethenyl]-1-[(2R,4S)-2-([[tert-butyl(dimethyl)silyl]oxy]methyl)-1,3-dioxolan-4-yl]-2,4(1H,3H)-pyrimidinedione		C₁₆H₂₅BrN₂O₅Si	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)