Troxacitabine, SPD-758, beta-L-OddC, BCH-4556, Troxatyl
4-氨基-1-[(2S)-2-(羟甲基)-1,3-二氧杂环戊-4-基]嘧啶-2-酮Chemical Name: (2'S,4'S)-1-[2-(Hydroxymethyl)-1,3-dioxolan-4-yl]cytosine; (2',4'S)-4-Amino-[2-(hydroxymethyl)-1,3-dioxolan-4-yl]pyrimidin-2-one; (-)-beta-L-Dioxolanecytidine
CAS No. 145918-75-8
项目整合开发状态: Phase III
项目研究机构: Shire Pharmaceuticals (Originator), Structural GenomiX (Licensee)
合成路线:Displacement of the chlorine atom of (I) with potassium benzoate in boiling DMF afforded benzoate ester (II).The hydroxymethyl group of (II) was subsequently oxidized to carboxylic acid (III) employing pyridinium dichromate.Conversion of acid (III) to the corresponding mixed anhydride with ethyl chloroformate,followed by Baeyer-Villiger oxidation with m-chloroperbenzoic acid,gave rise to the m-chlorobenzoyloxy dioxolane (IV).This was then coupled to cytosine (V) following a previously reported procedure to produce adduct (VI) as a cis/trans mixture.After acetylation with Ac2O,the desired cis-isomer (VII) was isolated by flash chromatography.The title compound was finally obtained by basic hydrolysis (VII).
📌 参考资料/链接：
参考文献标题:2-Substd.-4-substd.-1,3-dioxolanes,synthesis and use thereof
文献作者:Belleau,B.; Dixit,D.; Nguyen-Ba,N.(Shire BioChem Inc.)
参考来源:EP 0337713
📄 详细内容
合成路线:In a related procedure,1,6-anhydro-L-gulose (IX) was obtained from L-gulose (VIII) by treatment with 0.5 N HCl.Oxidative cleavage of (IX) by NaIO4,followed by reduction of the aldehyde groups with NaBH4,led to the dioxolane triol (X),which was further protected as the isopropylidene ketal (XI).Benzoylation of the free hydroxyl of (XI),followed by acidic hydrolysis of the acetonide group,furnished the benzoate diol (XII).Then,oxidation of the vicinal diol moiety of (XII),by means of RuO2 in the presence of NaIO4,afforded carboxylic acid (III).Oxidative decarboxylation of acid (III) with lead tetraacetate produced the key acetoxy dioxolane (XIII).This was coupled with the silylated N-acetylcytosine (XIV) in the presence of trimethylsilyl triflate to yield a mixture of anomers,which were separated by column chromatography.Final hydrolysis of the desired isomer (VII) was then performed by treatment with methanolic ammonia.
参考文献标题:Potent anti-HIV and anti-HBV activities of (-)-L-beta-dioxolane-C and (+)-L-beta-dioxolane-T and their asymmetric syntheses
文献作者:Kim,H.O.; et al.
参考来源:Tetrahedron Lett 1992,33(46),6899
产品链接: CAS No. 145918-75-8››