NOVEL SYNTHETIC APPROACHES TO ANTITUMOR COMPOUNDS

具有抗肿瘤活性的化合物在结构上有很大的差异。 制定方法和战略，以处理不同类别的此类问题 化合物需要允许系统的结构变化来发展 构效关系与新的生物候选者 作为临床候选人进行评估。例如，一个主要感兴趣的领域 修饰的核苷和碳核苷的发展是 抗肿瘤和抗病毒药物。过渡金属介电联轴器的使用 为这类化合物提供了一种新的策略，在潜在的 高效的流程。这类化合物在艾滋病治疗中的潜力 研究使该计划的这一阶段特别及时。那股力量 过渡金属催化的络合物合成反应 突出的是2β-羟基麻黄酮的方法，它检查 三个新反应：一个金属催化的[3+2]环加成反应，β-呋喃酮 合成和大环化反应。大环化还提供了 进入细胞毒剂紫草素。此外，这一合成 研究了一种新的非对映选择性策略，它调用了一种抗芳烃 通过过渡金属催化生成的中间体。紫杉烷， 它具有强大的临床有趣的抗肿瘤活性， 可以通过一种新的策略来接近，该策略涉及大环化和 跨环环化形成这个难以进入的环系。 引用催化概念的环化反应的全新方法 分子内氨基甲酸甲酯可提供有效的进入 临床证明的一类抗肿瘤药物鬼臼毒素，以及一种 叶黄酮苷是一类很有前途的临床抗肿瘤药物。这个 抗白血病药物罗格列胺可能在令人难以置信的短时间内就能达到 与取代的环戊环进行环加成反应的序列。一种新的 乙炔与乙烯基环氧化合物的偶联被认为是一种 以新卡西汀为代表的强大而独特的抗肿瘤药物。 金属催化环化反应的几何限制的松弛将 以临床上重要的抗肿瘤药物的策略为例 属于吡咯里西定家族的药物。了解肿瘤 促进对于了解肿瘤的起源也很重要。 制作。一种针对以 远程杀菌素探索了化学变色龙的概念。在大多数情况下， 战略还考虑了绝对立体化学的问题。

Compounds possessing antitumor activity vary greatly in their structures. Development of methodology and strategy to approach diverse classes of such compounds is required to permit systematic structural variation to develop structure-activity relationships and new candidates for biological evaluation as clinical candidates. For example, a major area of interest is the development of modified nucleosides and carbonucliosides as antitumor and antiviral agents. Use of transition metal mediated couplings offer a novel strategy to such compounds in a potentially greatly more efficient process. The potential of compounds of this class in AIDS research makes this phase of the program particularly timely. The power of transition metal catalyzed reactions for complex synthesis is highlighted by the approach to 2 beta-hydroxyjatrophone which examines three new reactions; a metal catalyzed [3+2] cycloaddition, beta-furanone synthesis, and macrocyclization. The macrocyclization also provides and entry to the cytotoxic agent shikodomedin. In addition, this synthesis examines a novel strategy for diastereoselectivity invoking an antiaromatic intermediate generated through transition metal catalysis. The taxanes, which possess members of potent clinically interesting antitumor activity, may be approached by a new strategy involving a macrocyclization and a transannular cyclization to form this difficultly accessible ring system. A totally new approach to cyclizations invoking the concept of catalytic intramolecular carbametallation may provide an effective entry to a clinically proven class of antitumor agents the podophyllotoxins, and a promising class of clinical antitumor agents, the phyllanthosided. The antileukemic agent, rocaglamide, may be accessible in an incredibly short sequence invoking a cycloaddition to substituted cyclopentryl rings. A new coupling of acetylenes with vinyl epoxides is proposed as an approach for the powerful and unusual antitumor agents represented by neocarzinostatin. The laxity of geometric limitations of metal catalyzed cyclizations will be exemplified by a strategy toward the clinically important antitumor agents belonging to the pyrrolizidine family. Understanding tumor promotion also is important to understanding the beginnings of tumor production. A strategy to one family of tumor promoters represented by teleocidin explores the concept of chemical chameleons. In most cases, the strategy also considers the problem of absolute stereochemistry.