STEREOSPECIFIC SYNTHESIS OF AMINOSUGAR ANTIBIOTICS

这项研究的总体目标将继续是开发新的 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，它们是 通过传统的碳水化合物操作相对难以获得。这 广义的分类包括各种各样的自然发生的 其集体药用性能跨越以下范围的物质 生物活性。这一阶段研究的代表性目标 包括米哈拉霉素、白霉素和埃佐霉素复合体--所有这些 它们的特征是非常不寻常的单糖残留量。没有一个 这些天然产物还没有合成出来。一个统一的结构 我们将重点关注的特征是将StereDefined 邻近的氨基醇盐部分进入这些非典型的糖结构。两者都有 “单向”和“双向”的链条延长策略将是 根据每个目标的需要进行部署。立体控制的装配 从氨基酸衍生的手性合成子开始的这样的系统将 将在我们实验室的结果基础上开发 之前的3年资助期。在这方面，我们还计划完成一项 正在进行的研究，系统地检查了对差异的添加 受保护的β-羟基-α-氨基醛。这些人的能力 在亲核加成过程中实施非对映界面控制的底物 通过1，2-不对称诱导进行了系统的探索。在以下方面取得成功 这些努力将提供有价值的方法，这些方法应该适用。 一系列相关的合成问题，并可能对各种 不对称诱导过程的一些方面也是如此。

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.