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紫杉醇氧杂环丁烷环D前体的合成与体外评价

Synthesis and In Vitro Evaluation of Taxol oxetane ring D precursors.

作者信息

Kaspera Rüdiger, Cape Jonathan L, Faraldos Juan A, Ketchum Raymond E B, Croteau Rodney B

机构信息

Institute of Biological Chemistry, Washington State University, Pullman, WA 99164-6340.

出版信息

Tetrahedron Lett. 2010 Apr 14;51(15):2017-2019. doi: 10.1016/j.tetlet.2010.02.033.

Abstract

A series of potential taxoid substrates was prepared in radiolabelled form to probe in vitro for the oxirane formation step and subsequent ring expansion step to the oxetane (ring D) presumably involved in the biosynthesis of the anticancer agent Taxol. None of the taxoid test substrates underwent transformation in cell-free systems from Taxus suggesting that these surrogates bore substitution patterns inappropriate for recognition or catalysis by the target enzymes, or that taxoid oxiranes and oxetanes arise by independent biosynthetic pathways.

摘要

制备了一系列放射性标记形式的潜在紫杉烷类底物,用于体外探测环氧乙烷形成步骤以及随后推测参与抗癌药物紫杉醇生物合成的向氧杂环丁烷(D环)的环扩展步骤。紫杉烷类测试底物在来自红豆杉的无细胞系统中均未发生转化,这表明这些替代物的取代模式不适用于目标酶的识别或催化,或者紫杉烷类环氧乙烷和氧杂环丁烷是通过独立的生物合成途径产生的。

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本文引用的文献

1
Taxol biosynthesis and molecular genetics.
Phytochem Rev. 2006 Feb;5(1):75-97. doi: 10.1007/s11101-005-3748-2.
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Molecular cloning and characterization of a cytochrome P450 taxoid 2alpha-hydroxylase involved in Taxol biosynthesis.
Arch Biochem Biophys. 2004 Jul 1;427(1):48-57. doi: 10.1016/j.abb.2004.04.016.

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