SYNTHESIS OF ANTIBIOTIC AND ION TRANSPORT AGENTS

这项研究的目标是合成有机化学和生物有机化学 是合成天然抗生素的离子载体和大环内酯类 并设计、合成和研究仿生杂化分子 含有大环氢吡喃低聚物。具体目标是 具体描述如下： 1.“第二代”大环氢吡喃齐聚物的合成 具有用于基本络合研究的定向官能团， 聚集和离子传输现象，包括： (A)设计好的、结构明确的模板，用于组装和 两亲性螺旋多肽束的仿生特性 跨膜离子通道； (B)水二聚体的构象有利的宿主，具有 在延伸的管状结构中作为自组装亚单位的潜力 超分子阵列； (C)具有自我补充功能的其他模板 “严格”(可逆)自组装成管状超分子 离子对或氢键相互作用； (D)含有咪唑和巯基的有序模板 生理条件下两种自组装模式的研究进展 条件，具有作为手性蛋白酶模拟物的潜在应用。 2.全合成天然离子载体灰黄素(ZinCophorin)， 特点： (A)只需要19个线性步骤的三重收敛路线 立体(13个不对称)中心； (B)反式自由基和阴离子的直接比较 无环背景下的氢化吡喃-乙烯基砜偶联 立体控制。 3.完成了一种合成聚丙酸酯大环内酯的新方法， 以赤潮内酯B和赤潮内酯A为例，其特征是： (A)利用拟对称的C2-和C6和C8-&GT；C12区 二(二氢吡喃)模板； (B)二氧杂环己酮到二氢吡喃的双重重排，以建立 完整的Cl-&GT；C13阵列； (C)同时进行多重氢化反应，以引入几个 一次中心不对称； (D)第二酸As构象限制的新策略 对大内酯化的一种信息量辅助。

The goals of this research in synthetic organic and bioorganic chemistry are to synthesize natural antibiotics of the ionophore and macrolide classes and to design, synthesize, and study biomimetic hybrid molecules Incorporating macrocyclic hydropyran oligolides. Specific objectives are described below: 1 . Synthesis of 'second generation' macrocyclic hydropyran oligolides with directed functionality for the study of fundamental complexation, aggregation, and ion transport phenomena, including: (a) designed, structurally well-defined templates for assembling and characterizing amphiphilic helical peptide bundles as biomimetic transmembrane ion channels; (b) a conformationally favorable host for the water dimer, with potential as a self-assembling subunit in an extended, tubular supramolecular array; (c) other templates with self-complementary functionality for 'strict' (reversible) self-assembly into tubular supramolecules bound by ion pair or H-bonding interactions; (d) an ordered template Incorporating imidazole and sulfhydryl moieties to study two modes of self-assembly under physiological conditions, with potential application as a chiral proteinase mimic. 2. Total synthesis of the natural ionophore griseochelin (zincophorin), featuring: (a) a triply convergent route requiring only 19 linear steps for 17 stereogenic (13 asymmetric) centers; (b) direct comparison of anomeric radical and anionic hydropyran-to-vinylsulfone couplings in the context of acyclic stereocontrol. 3. Completion of a novel approach to polypropionate macrolides, exemplified by erythronolide B and erythronolide A, featuring: (a) exploitation of pseudosymmetrical C2->C6 and C8->C12 regions via a bis(dihydropyran) template; (b) double dioxanone-to-dihydropyran rearrangement to establish intact Cl->C13 array; (c) simultaneous multiple hydroborations to introduce several asymmetric centers at once; (d) a novel tactic for conformational restriction of the seco acid as an entropic aid to macrolactonization.