Modeling of Complex Polyketides: Stereochemical Determination by a Combination of Computational and NMR Methods
Modeling of Complex Polyketides: Stereochemical Determination by a Combination of Computational and NMR Methods
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复杂聚酮化合物的建模：结合计算和 NMR 方法进行立体化学测定
DOI：
10.1002/9783527636402.ch24
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
D. Menche
中科院分区：
文献类型：
--
作者：
S. Dreisigacker;D. Menche
从结构上讲，聚酮是一类不同的天然代谢物，具有广泛的生物活性。事实上，聚酮类抗生素、抗真菌药物、细胞抑制剂、抗寄生虫剂和天然杀虫剂目前在商业基础上被广泛使用。在生物合成方面，聚酮是由乙酰基和丙酰亚基的迭代缩合而来的，产生了不同的含甲基和含羟基的立体生成中心的组装，使得大量的立体化学排列成为可能。不幸的是，这种多样性，再加上高度的光谱复杂性和构象灵活性，使得聚酮类化合物的立体化学指定成为一个主要的挑战。粘细菌是新型多酮的一种特别丰富的来源[1，2]，在过去的三十年里-基于Helmholtz-Zentum für Infektionsforschung(HZI布伦施韦格感染研究中心)Höfle和Reichenbach教授团队进行的开创性调查结果-从这些土壤生物中分离出了一系列结构独特和生物合成多样化的多酮。总体而言，这些材料涵盖了大约60个结构上新的聚酮类及其许多结构变体。最突出的是，埃博西酮是来自纤维粘杆菌的天然抗增殖剂(图24.1)，已被开发并被批准为治疗转移性和晚期乳腺癌的抗癌药物。对这些代谢产物进行了广泛的生物学研究，并对这些微管稳定剂进行了计算和基于核磁共振的分析，随后开发了它们发酵和合成的详细工艺[3]。与大环内酯类化合物相比，许多其他聚酮类化合物的开发要落后得多，尽管它们具有类似的生物学特性，包括抗增殖、抗生素、抗真菌或抗疟原虫活性。同样，在许多情况下，从细胞骨架、核酸聚合酶、呼吸链、核运输、
In structural terms, the polyketides are a diverse class of natural metabolites characterized by a broad range of biological activities. Indeed, polyketide antibiotics, antifungals, cytostatics, antiparasitics and natural insecticides are currently widely used on a commercial basis. Biosynthetically, the polyketides are derived by iterative condensations of acetyl and propionyl subunits, giving rise to diverse assemblies of methyl-and hydroxyl-bearing stereogenic centers that enable large numbers of stereochemical permutations. Unfortunately, this diversity–together with a high degree of spectral complexity and conformational flexibility–causes the stereochemical assignment of polyketides to become a major challenge. The myxobacteria are a particularly rich source of novel polyketides [1, 2], and over the past three decades–based on the results of pioneering investigations conducted by the groups of Professors Höfle and Reichenbach at the Helmholtz-Zentrum für Infektionsforschung (Center for Infection Research in Braunschweig, HZI)–an impressive range of structurally unique and biosynthetically diverse polyketides has been isolated from these soil-living organisms. In total, these materials span a range of approximately 60 structurally new polyketide classes, and many structural variants thereof. Most prominently, the epothilones are natural antiproliferative agents from the myxobacterium Sorangium cellulosum (Figure 24.1), that have been developed and approved as anticancer drugs for the treatment of metastatic and advanced breast cancer. Extensive biological studies, as well as computational and NMR-based analyses of these microtubule-stabilizing agents, have been reported for these metabolites, and detailed processes for their fermentative and synthetic production have subsequently been developed [3].In contrast to the macrolides, many other polyketides are much less advanced in their development, despite having similarly promising biological profiles that include antiproliferative, antibiotic, antifungal, or antiplasmodial activities. Likewise, in many cases targets are specifically addressed on a molecular level, ranging from the cytoskeleton, nucleic acid polymerases, the respiratory chain, nuclear transport,
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影响因子：
2.7
作者：
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通讯作者：
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影响因子：
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作者：
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根足素是一种来自粘细菌（粘细菌）的新化合物，可在动物细胞培养物中引起根足样结构的形成。
DOI：
10.7164/antibiotics.46.741
发表时间：
1993
期刊：
The Journal of antibiotics
影响因子：
--
作者：
F. Sasse;H. Steinmetz;G. Höfle;H. Reichenbach
通讯作者：
H. Reichenbach
影响因子：
4.9
作者：
Horstmann, Nicole;Menche, Dirk
通讯作者：
Menche, Dirk