SYNTHESIS OF ANTIBIOTICS

该项目的长期目标包括开发新的 合成策略和这些策略的应用 生物学感兴趣的复杂系统的合成。 在AI程序中 我们希望将这些能力应用于合成 有兴趣作为潜在抗生素、抗病毒剂或抗肿瘤剂 毒品 在下一个资助期内，我们将重点关注广泛的化学品 具有不同生物学意义的目标。 一个主要的和全面的 在寡糖的合成中设想了努力。 我们将研究 一个潜在的反应菜单，其中糖化物将是底物， 亲电诱导的糖苷化。 在这项工作中包括2- 脱氧、2-卤代、2-氨基和“正常”2-氧化寡糖。 的 最终目标是开发基于聚合物的 寡糖构建。 碳水化合物领域的具体目标 将是阿维菌素和阿霉素的新糖苷，以及 allosamidin的全部碳水化合物部分。 一项关于使用这些 合成抗艾滋病新核苷的概念 治疗将启动。 在杂环化合物的合成中，发展了一些新的策略。 这些发现的应用，以全合成的几个关键 目标系统将继续进行。 在这方面特别有趣 是栗精胺和FR 900482。 栗精胺已被证明具有 一些抗艾滋病的潜力，作为酶的抑制剂， 糖蛋白成熟 FR 900482引起了相当大的兴趣 由于其非常新颖的结构和报告“异常有效” 抗肿瘤活性。 我们还将作出大量努力， 埃斯帕霉素。 在这方面，挑战超出了 合成问题 通过合适的结构，可以获得 独特的通过合成，更好地了解作用方式， 这一重要的抗肿瘤药物将实现。 一个主要的努力将指向FK-506的全合成。 这种化合物是目前已知的最强大的免疫抑制剂（超过100种）。 比环孢菌素活性高）。 我们也将继续我们的醌- 仿生化学背景下的氢醌化学 阿霉素 通过这些研究， 将寻求antaracyclines的作用。 结束我们的 设想在衣霉素领域中的努力。 目前， 唯一剩下的问题是构建海藻糖型的 联动

The long-term objectives of this project involve the development of new synthetic strategies and the application of these strategies to the synthesis of complex systems of biological interest. In the AI program we hope to apply these capabilities to the synthesis of substances of interest as potential antibiotics, antiviral agents, or as antitumor drugs. In this next grant period we will focus on a broad range of chemical goals with diverse biological implications. A major and comprehensive effort is envisioned in the synthesis of oligosaccharides. We will study a potential menu of reactions whereby glycals will be substrates for electrophilically induced glycosidation. Included in this work are 2- deoxy, 2-halo, 2-amino, and "normal" 2-oxygenated oligosaccharides. The ultimate goal is the development of a capability in polymer based oligosaccharide construction. Specific targets in the carbohydrate area will be novel glycosides of avermectin and adriamycin, as well as the full carbohydrate portion of allosamidin. A study of the use of these concepts for the synthesis of novel nucleosides of interest in anti-AIDS therapy will be launched. Some new strategies in the synthesis of heterocycles have been developed. The application of these findings to the total synthesis of several key target systems will be pursued. Particularly interesting in this regard are castanospermine and FR900482. Castanospermine has been shown to have some anti-AIDS potential as an inhibitor of enzymes responsible for glycoprotein maturation. FR900482 has engendered considerable interest due to its very novel structure and reported "exceptionally potent" antitumor activity. We also will be directing a great deal of effort to the synthesis of esperamicin. Here the challenge goes beyond the complexity of the synthetic problem. Through suitable structures, which can be obtained uniquely through synthesis, a better understanding of the mode of action of this important antitumor agent will be achieved. A major effort will be directed toward the total synthesis of FK-506. This compound is the most powerful immunosuppressant now known (100 more active than cyclosporine). We will also continue our quinone- hydroquinone chemistry in the context of the biomimetic chemistry of adriamycin. Through these studies a superior insight into the mode of action of the antaracyclines will be sought. The completion of our efforts in the tunicamycin area is envisioned. At the present time the only remaining problem is the construction of the trehalose type of linkage.