STEREOSPECIFIC SYNTHESIS OF AMINOSUGAR ANTIBIOTICS

氨基糖抗生素的立体定向合成

• 批准号: 3288514
• 负责人: PHILIP P GARNER
• 金额: $ 11.14万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-06-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3288514
• 关键词: aminoacid; aminosugar; antibiotics; drug design /synthesis /production; nuclear magnetic resonance spectroscopy; stereochemistry

The overall goal of this study will continue to be the development of new strategies and synthetic methodologies for the stereocontrolled assembly of structurally complex aminosugar (nucleoside) antibiotics which are relatively inaccessible via traditional carbohydrate manipulation. This broad classification encompasses a wide variety of naturally occurring substances whose collective medicinal properties span the spectrum of biological activity. Representative targets for this phase of the study include the miharamycins, the albomycins, and the ezomycin complex - all of which are characterized by highly unusual monosaccharide residues. None of these natural products have yet been synthesized. A unifying structural feature upon which we will focus is the incorporation of stereodefined vicinal aminoalkoxide moieties into these atypical sugar structures. Both "unidirectional" and "bidirectional" chain elongation strategies will be employed as required for each target. The stereocontrolled assembly of systems such as these starting from aminoacid derived chiral synthons will be developed building on results obtained in our laboratory during the previous 3-year grant period. In this context we also plan to complete an ongoing study which systematically examined additions to differentially protected beta-hydroxy-alpha-aminoaldeydes. The ability of these substrates to exert diastereofacial control during nucleophilic additions via 1,2-asymmetric induction will be explored systematically. Success in these endeavors will provide valuable methodology that should be applicable to a number of related synthetic problems and may shed light on various aspects of the asymmetric induction process as well.

本研究的总体目标将继续是开发新的 的立体控制组装的策略和合成方法 结构复杂的氨基糖（核苷）抗生素， 通过传统的碳水化合物处理相对难以获得。 这 广泛的分类包括各种各样的天然存在的 这些物质的集体药用特性跨越了 生物活性 本研究阶段的代表性目标 包括miharamycins、albomycins和ezomycin复合物--所有的 其特征在于非常不寻常的单糖残基。 没有一 这些天然产物尚未被合成。 统一的结构 我们将重点关注的特征是将立体定义的 邻位氨基醇盐部分进入这些非典型糖结构。 两 “单向”和“双向”链延伸策略将是 根据每个目标的需要。 立体控制组装 诸如这些起始于氨基酸衍生的手性配体的体系将 基于我们实验室在 上一个三年补助期。 在这方面，我们还计划完成一项 正在进行的一项研究，系统地审查了不同 保护的β-羟基-α-氨基醛。 这些能力 在亲核加成过程中发挥非对映体控制作用的底物 通过1，2-不对称诱导将进行系统的探索。 成功 这些努力将提供有价值的方法， 许多相关的合成问题，并可能揭示各种 不对称诱导过程的各个方面。