ENANTIOSELECTIVE SYNTHESIS OF NATURAL PRODUCTS

下一个赠款期间的一个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 方法将应用于合成具有以下特点的天然产物 具有生物活性和/或药用活性；预计 Windaus-Grundmann酮的不对称全合成 重要的维生素D合成中间体将在 下一个授权期。我们将开始对映体选择性的全合成 ()-Quassin，三萜类Quassin家族的成员 因为它们具有广泛的生物学特性而引起人们的兴趣， 包括抗白血病活性。当完成时，完全合成 ()-夸辛将展示对映体选择性白桦树的效用 还原烷基化策略适用于要求异常苛刻的 合成靶标。一种不对称全合成哈斯巴烷的方法 生物碱()-脑胺将显示出分子内的1，5-芳香族 在角碳原子上的环结构，这个过程应该有 在复杂生物碱和萜类化合物结构中的普遍用途。一个 (-)Delta9，12-Capnellene的对映选择性全合成 串联分子内Diels-Alder环加成反应的新应用 氧-二-皮-甲烷光重排反应。 预计我们最近报道的立体选择性偶联物 加成方法将应用于新的环烯酮以及 杂环体系和非环烯类化合物。此方法适用于不对称 与上一次拨款期间发起的其他项目一起进行综合 将在生物碱和萜类化合物的范围内进行审查 综合。 下一个赠款期间的另一个主要目标是发展 手性联芳基衍生物的制备和应用方法 通过光重排得到对映体纯净的形式 吗啡生物碱的衍生物。建议C(2) 空间位阻增大的对称双齿配体 在2，2‘-二羟基-1，1’-联芳基单元的侧翼位置 可通过对商业可待因和西巴因的简单修改而获得。 手性配体将在不对称Lewis酸促进下进行考察 Diels-Alder环加成、烯反应和Claisen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.