Brovavir, Sorivudine, BV-araU, SQ-32756, YN-72, BVAU, Bravavir, Usevir, -Drug Synthesis Database

【结构式】

【药物名称】Brovavir, Sorivudine, BV-araU, SQ-32756, YN-72, BVAU, Bravavir, Usevir

【化学名称】(+)-1-beta-D-Arabinofuranosyl-5-[(E)-2-bromovinyl]uracil
　　　　　　(+)-(E)-1-beta-D-Arabinofuranosyl-5-(2-bromoethenyl)-2,4(1H,3H)-pyrimidinedione

【CA登记号】77181-69-2

【分子式】C₁₁H₁₃BrN₂O₆

【分子量】349.14006

【开发单位】Yamasa Shoyu (Originator), Azwell (Licensee), Bristol-Myers Squibb (Licensee), Eisai (Licensee)

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

合成路线1 合成路线2

合成路线1

A new synthesis of BVAU has been described: The condensation of 1-(beta-D-arabinofuranosyl)-5-formyluracil (I) with malonic acid (II) by means of piperidine in hot anhydrous pyridine gives the carboxyvinyl derivative (III), which is then treated with N-bromosuccinimide in basic medium.

参考文献中间体

【1】 Sakata, S.; Machida, H.; Kumagai, M.; Yamaguchi, T.; Ikeda, K.; Synthesis of 14C-labelled 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl) uracil (BV-araU). J Label Compd Radiopharm 1989, 27, 5, 503.

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)	10112	1-[(2R,3S,4S,5R)-3,4-Dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinecarbaldehyde		C₁₀H₁₂N₂O₇	详情	详情
(II)	12963	Malonic acid	141-82-2	C₃H₄O₄	详情	详情
(III)	10114	(E)-3-[1-[(2R,3S,4S,5R)-3,4-Dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]-2-propenoic acid		C₁₂H₁₄N₂O₈	详情	详情

合成路线2

Treatment of 5-hydroxymethyl-1-beta-D-arabinofuranosyluracil (I) with hydrogen chloride in dioxane affords the 5-chloromethyl derivative (II), which is converted to the triphenylphosphonium salt (III). The Wittig reaction of (III) by means of paraformaldehyde and n-butyllithium in DMF yields the 5-vinyl derivative (IV), and bromination of (IV) with bromine in DMF under a heated condition affords BVAU.

参考文献中间体

【1】 Senda, S.; Mizuno, Y.; Shibuya, S.; Ikeda, K.; Sakata, S.; Machida, H.; Hirota, K.; Yoshino, H.; Synthesis and antiherpes-viral activity of 5-C-substituted uracil nucleosides. Nucleic Acids Res Symp Ser 1980, 8, 8, S39-S42.
【2】 Sakata, S.; Machida, H.; BVAU. Drugs Fut 1982, 7, 7, 458.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	32130	1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-(hydroxymethyl)-2,4(1H,3H)-pyrimidinedione; 5-hydroxymethyl-1-beta-D-arabinofuranosyluracil	C₁₀H₁₄N₂O₇	详情	详情
(II)	32131	5-(chloromethyl)-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2,4(1H,3H)-pyrimidinedione	C₁₀H₁₃ClN₂O₆	详情	详情
(III)	32132	([1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]methyl)(triphenyl)phosphonium chloride	C₂₈H₂₈ClN₂O₆P	详情	详情
(IV)	32133	1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-vinyl-2,4(1H,3H)-pyrimidinedione	C₁₁H₁₄N₂O₆	详情	详情

Extended Information