Brivudine, Bromovinyldeoxyuridine, RP-101, A-176, BVDU, Zostex, Helpin, -Drug Synthesis Database

【结构式】

【药物名称】Brivudine, Bromovinyldeoxyuridine, RP-101, A-176, BVDU, Zostex, Helpin

【化学名称】(E)-5-(2-Bromovinyl)-2'-deoxyuridine

【CA登记号】69304-47-8

【分子式】C₁₁H₁₃BrN₂O₅

【分子量】333.14066

【开发单位】Berlin-Chemie (Originator), Menarini (Originator), Rega Institute for Medical Research (Originator), Vinas (Licensee)

【药理作用】Anti-Herpes Virus Drugs, ANTIINFECTIVE THERAPY, Antiviral Drugs, Reverse Transcriptase Inhibitors

合成路线1 合成路线2

合成路线1

The condensation of 2-deoxy-3,5-di-O-(phenylacetyl)-beta-D-erythro-pentofuranosyl chloride (I) with 2,4-bis-O-(trimethylsilyl)-5(E)-(2-bromovinyl)uracil (II) in acetonitrile (Lewis acid catalyst), or in CHCl3-pyridine (Bronsted acid catalyst), gives 3',5'-di-O-(phenylacetyl)-5(E)-(2-bromovinyl)-2'-deoxyuridine (III) and its anomer that is eliminated by TLC (silicagel). Finally, (III) is treated with sodium methoxide in methanol.

参考文献中间体

【1】 Kulikowski, T.; Felczak, K.; Poznanski, J.; Remin, M.; Novel syntheses and solution conformations of (E)-5-(2-bromovinyl)-2'-deoxyuridine. Int Symp: Basic Clin Approach Virus Chemother 1988, Poster M17.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	21095	5-chloro-2-[[(2-phenylacetyl)oxy]methyl]tetrahydro-3-furanyl 2-phenylacetate	C₂₁H₂₁ClO₅	详情	详情
(II)	21096	5-[(E)-2-bromoethenyl]-2,4-bis[(trimethylsilyl)methyl]pyrimidine	C₁₄H₂₅BrN₂Si₂	详情	详情
(III)	21097	5-[5-[(E)-2-bromoethenyl]-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-2-[[(2-phenylacetyl)oxy]methyl]tetrahydro-3-furanyl 2-phenylacetate	C₂₇H₂₅BrN₂O₇	详情	详情

合成路线2

5-Chloromercuri-2'-deoxyuridine (II) is prepared from 2'-deoxyuridine (I) by reaction with mercuriacetate and natrium chloride (1). Condensation of (II) with ethylacrylate (A) and lithium palladium chloride gives (E)-5-(2-carbethoxyvinyl)-2'-deoxyuridine (III), which is readily hydrozyled to (E)-5-(2-carboxyvinyl)-2'-deoxyuridine (IV) under basic conditions (0.5M NaOH). The final step involves the reaction of (IV) with N-bromosuccinimide to produce (E)-5-(2-bromovinyl)-2'-deoxyuridine.

参考文献中间体

【1】 Bergstrom, D.E.; Ruth, J.L.; Preparation of C-5 mercurated pyrimidine nucleosides. J Carbohydates Nucleosides Nucleotides 1977, 4, 5, 4415.
【2】 De Clercq, E.; Bromovinyldeoxyuridine. Drugs Fut 1980, 5, 7, 334.
【3】 Jones, A.S.; et al.; The synthesis of the potent antiherpes virus agent, E-5(2-bromovinyl)-2'-deoxyuridine and related compounds. Tetrahedron Lett 1979, 45, 4415-8.

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)	10164	ethyl acrylate	140-88-5	C₅H₈O₂	详情	详情
(I)	11875	1-[(2R,4S,5R)-4-Hydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2,4(1H,3H)-pyrimidinedione; 2'-Deoxyuridine	951-78-0	C₉H₁₂N₂O₅	详情	详情
(II)	39186	chloro[1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]mercury		C₉H₁₁ClHgN₂O₅	详情	详情
(III)	39187	ethyl (E)-3-[1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]-2-propenoate		C₁₄H₁₈N₂O₇	详情	详情
(IV)	39188	(E)-3-[1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]-2-propenoic acid		C₁₂H₁₄N₂O₇	详情	详情

Extended Information