ENANTIOSELECTIVE SYNTHESIS OF NATURAL PRODUCTS

下一个赠款期的一个主要目标是进一步发展 芳族羧酸的对映选择性转化方法 用于有机合成的手性衍生物到手性中间体。 这些 方法将应用于天然产物的合成， 具有生物学和/或医学活性;预计 Windaus-Grundmann酮的对映选择性全合成， 一个重要的维生素D合成中间体将在2015年完成。 下一个补助期 我们将开始对映选择性全合成 （+）-苦木素，苦木素类三萜家族的成员， 由于其广泛生物学特性， 包括抗白血病活性。 当完成了全合成， （+）-苦木素将证明对映选择性Birch 还原烷基化策略，适用于一个非常苛刻的 综合目标 对映选择性全合成Hasbanane 生物碱（+）-头孢拉胺将显示分子内1+5芳香族 在有角的碳原子上的环结构，这一过程应该具有 在复杂生物碱和萜类化合物构建中的通用性。 一个 （-）δ 9，12-Capnellene的对映选择性全合成的特征在于 串联分子内Diels-Alder环加成反应的新用途 和氧杂-二-π-甲烷光重排。 预期我们最近报道的立体选择性缀合物 加成方法将应用于新的环烯酮，以及 杂环系统和无环烯酮。 该方法用于不对称 沿着过去赠款期间启动的其他项目的综合 期间将在生物碱和萜类化合物的背景下进行检查 合成. 下一个赠款期的另一个主要目标是发展 制备和利用手性联芳基衍生物的方法 通过光重排以对映体纯的形式获得 吗啡生物碱的衍生物。 建议C（2） 空间位阻增加的对称双齿配体 在2，2 ′-二羟基-1，1 ′-联芳基单元侧翼的位置处， 可通过对商业可待因和蒂巴因进行简单修饰而获得。 手性配体将在不对称刘易斯酸促进的 狄尔斯-阿尔德环加成，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.