CAS: 28008-55-1; 13-Dihydrodaunorubicin

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CAS号20830-81-3 柔红霉素

📜道诺霉素置于recombinant Human Carbonyl Reductase Isoform 3 With Amino-Terminal His6 Tag,还原型辅酶ii(Nadph)四钠盐体系中,用 乙醇 用作溶剂,化学反应 0.5H,反应生成柔红霉素
参考文献:Naturally occurring Variants Of Human Cbr3 Alter Anthracycline In Vitro Metabolism
标题:Naturally occurring Variants Of Human Cbr3 Alter Anthracycline In Vitro Metabolism
摘要:多柔比星(doxorubicin,Dox)和达乌诺比星(daunorubicin,Daun)是蒽环类抗癌药;然而,它们的药代动力学在患者之间存在相当大的差异.这种患者间的差异部分归因于编码羰基还原酶的基因中的非同义单核苷酸多态性(ns-Snps)改变了代谢.本研究探讨了 Cbr3 基因中七种天然存在的 Ns-Snps 对蒽环类药物体外代谢为多柔比星醇和达乌比星醇的影响.动力学测定法利用纯化的组氨酸标记的人 Cbr3 野生型和变异型酶,通过高效液相色谱分离和荧光检测来测量代谢物水平.与野生型酶相比,V224M,C4Y 和 V93I 变体导致两种蒽环类化合物的最大反应速度(v Max)显著降低,而 M235L 变体仅导致 Dox 的最大反应速度显著降低.发现 V244M 变体对 Daun 以及 C4Y 和 V93I 变体对 Dox 的底物亲和力都有显著提高.对于 Daun 和 Dox,V244M,C4Y 和 V93I 变体的催化效率值明显低于野生型.此外,对于野生型酶及其变体来说,Dox 是比 Daun 更好的底物.Hapmap分析表明,在hapmap项目研究的11个种族人群中,可能会出现携带c4Y和v244M突变的单倍型.我们制备的双突变体与野生型酶和单突变体相比,活性明显降低.这些发现表明,人类 Cbr3 中常见的 Ns-Snps 会显著改变 Dox 和 Daun 的体外代谢.
Doi:10.1124/jpet.109.160614

专利信息

专利号:US-8802830-B2
优先权日:2005-12-20
标题 :Synthesis of epirubicin from 13-dihydrodaunorubicine
发明人：ZABUDKIN ALEXANDER F; MATVIENKO VICTOR; ITKIN ALEKSANDR M; MATVEEV ALEXEY
权利人:ZABUDKIN ALEXANDER F; MATVIENKO VICTOR; ITKIN ALEKSANDR M; MATVEEV ALEXEY; SOLUX CORP
摘要:A method of preparing an anthracyclin such as epirubicin from a starting material comprising 13-dihydrodaunorubicine (13-daunorubicinol). The method comprises producing N-Trifluoroacetyl-13-daunorubicinol from 13-daunorubicinol by acylation. The N-Trifluoroacetyl-13-daunorubicinol is reacted with an aprotic solvent and an acylating agent to produce an intermediate sulfoxy salt which is treated with a strong base to produce 4′-keto-N-Trifluoroacetyldaunorubicin. The 4′-keto-N-Trifluoroacetyldaunorubicin is reacted with a reducing agent, such as borohydride of an alkaline metal, to produce N-Trifluoroacetyl-4′-epi-daunorubicin. The N-Trifluoroacetyl-4′-epi-daunorubicin is hydrolyzed in a basic solution to produce an intermediate compound. The intermediate compound is reacted with a halogenizing agent to produce a 14-Hal-derivative. The 14-Hal derivative is hydrolized in the presence of a formate of an alkaline metal to produce the desired final compound.

专利号:US-2007142309-A1
优先权日:2005-12-20
标 题 :Synthesis of epirubicin from 13-dihydrodaunorubicine

专利号:EP-1963348-B1
优先权日:2005-12-20
标题:Synthesis of epirubicin from 13-dihydrodaunorubicine

专利号:EP-1963348-A4
优先权日:2005-12-20
标 题:SYNTHESIS OF EPIRUBICIN FROM 13-DIHYDRODAUNORUBICIN

专利号:CN-101341166-B
优先权日:2005-12-20
标题:Synthesis of epirubicin from 13-dihydrodaunorubicine

专利号:AT-E499377-T1
优先权日:2005-12-20
标题:SYNTHESIS OF EPIRUBICIN FROM 13-DIHYDRODAUNORUBICIN