SYNTHESIS OF ANTIBIOTIC AND ION TRANSPORT AGENTS

本研究的目标是合成有机化学和生物有机化学 是合成离子载体和大环内酯类天然抗生素， 类和设计，合成和研究仿生混合分子 制备大环氢吡喃低聚物。 具体目标是 描述如下： 1 .一、第二代大环吡喃低聚物的合成 具有用于基础络合研究的定向功能， 聚集和离子传输现象，包括： (a)设计的，结构明确的模板，用于组装和 两亲性螺旋肽束的仿生表征 跨膜离子通道 (b)水二聚体的构象上有利的主体， 作为一个自组装亚单位的潜力，在一个扩展的，管状的 超分子阵列; (c)其他具有自我补充功能的模板， “严格”（可逆）自组装成管状超分子， 离子对或氢键相互作用; (d)咪唑和巯基有序模板 部分研究两种模式的自组装在生理 条件下，作为手性蛋白酶模拟物的潜在应用。 2. 天然离子载体灰螯铁蛋白（锌磷蛋白）的全合成， 特色： (a)一条三重收敛的路线，17步只需要19个线性步骤， 立体异构（13个不对称）中心; (b)端基和阴离子的直接比较 在无环的情况下的氢吡喃与乙烯基砜的偶联 立体控制 3.合成聚丙酸酯大环内酯的新方法的完成， 例如，以双头龙B和双头龙A为例，其特征在于： (a)利用假对称C2->C6和C8->C12区域， 双（二氢吡喃）模板; (b)双二氧环己酮-二氢吡喃重排， 完整的Cl->C13阵列; (c)同时进行多次硼氢化反应， 不对称中心同时存在; (d)一种新的策略，构象限制的开环酸， 有助于大环内酯化的熵。

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.