ENANTIOSELECTIVE SYNTHESIS OF NATURAL PRODUCTS

下一个资助期的主要目标是进一步发展 芳香族羧酸的对映选择性转化方法 用于有机合成的手性中间体的衍生物。 这些 方法将被应用于天然产物的合成 具有生物和/或药用活性；预计 Windaus-Grundmann 酮的对映选择性全合成 重要的维生素D合成中间体将在此期间完成 下一个资助期。 我们将开始对映选择性全合成 ( )-quassin，三萜类木木素家族的成员 由于其广泛的生物学特性而引起人们的兴趣， 包括抗白血病活性。 当完成全合成时 ( )-quassin 将展示对映选择性 Birch 的实用性 还原烷基化策略应用于异常苛刻的 合成目标。 哈巴烷的对映选择性全合成 生物碱 ( )-头孢拉明将表现出分子内 1 5 芳香族 在角碳原子上构建环，这个过程应该有 在复杂的生物碱和萜类化合物结构中具有普遍用途。 安 (-)delta9,12-capnellene 的对映选择性全合成具有以下特点 串联分子内第尔斯-阿尔德环加成的新用途 和氧杂-二-π-甲烷光重排。 预计我们最近报道的立体选择性缀合物 添加方法将应用于新的环烯酮，以及 杂环系统和无环烯酮。 这种方法对于非对称 与过去赠款期间启动的其他项目一起进行综合 期间将在生物碱和萜类化合物的背景下进行检查 合成。 下一个资助期的另一个主要目标是开发 手性联芳基衍生物的制备方法和用途 通过光重排获得对映体纯形式 吗啡生物碱的衍生物。 建议C(2) 空间位阻程度不断增加的对称二齿配体 在 2,2'-二羟基-1,1'-联芳基单元侧翼的位置将是 通过对市售可待因和蒂巴因进行简单修饰即可获得。 手性配体将在不对称路易斯酸促进下进行检查 Diels-Alder 环加成、烯反应和克莱森重排。

A major goal for the next grant period is the further development of methods for the enantioselective conversion of aromatic carboxylic acid derivatives to chiral intermediates for use in organic synthesis. These methods will be applied to the synthesis of natural products that possess biological and/or medicinal activity; it is expected that an enantioselective total synthesis of the Windaus-Grundmann ketone, an important vitamin D synthetic intermediate will be completed during the next grant period. We will begin an enantioselective total synthesis of (+)-quassin, a member of the quassinoid family of triterpenes of interest because of their wide spectrum of biological properties, including antileukemic activity. When completed the total synthesis of (+)-quassin will demonstrate the utility of the enantioselective Birch reductive alkylation strategy as applied to an unusually demanding synthesis target. An enantioselective total synthesis of hasbanane alkaloid (+)-cepharamine will demonstrate an intramolecular 1+5 aromatic ring construction at an angular carbon atom, a process that should have general utility in complex alkaloid and terpenoid construction. An enantioselective total synthesis of (-)delta9,12-capnellene features a novel utilization of the tandem intramolecular Diels-Alder cycloaddition and oxa-di-pi-methane photorearrangement. It is expected that our recently reported stereoselective conjugate addition methodology will be applied to new cycloalkenones, as well as heterocyclic systems and acyclic enones. This method for asymmetric synthesis along with other projects initiated during the past grant period will be examined within the context of alkaloid and terpenoid synthesis. Another major goal for the next grant period is the development of methods for preparation and utilization of chiral biaryl derivatives to be obtained in enantiomerically pure form by photorearrangement of derivatives of the morphine alkaloids. It is proposed that C(2) symmetric bidentate ligands with increasing degrees of steric hindrance at positions flanking the 2,2'-dihydroxy-1,1'-biaryl unit will be available by simple modifications of commercial codeine and thebaine. The chiral ligands will be examined in asymmetric Lewis acid promoted Diels-Alder cycloadditions, ene reactions, and Claisen rearrangements.