Heterocumulenes in Asymmetric Catalysis

这项提议的具体目的和长期目标是使用杂聚烯(烯酮， 酮亚胺及其合成类似物)在不对称催化中的新应用，即 对内酰胺类(特别是反式非对映异构体)的不对称合成、催化不对称卤化反应 (氯化、溴化和碘化)和催化不对称a-硝化。我们还提出了 新型双功能(Lewis酸-手性亲核试剂)催化不对称反应的研究进展，包括 烯醇酸酯的[2+2]和[4+2]环加成反应。我们所有手性、光学富集型产品 反应要么具有药理活性，要么代表关键的中间体和分支。 在医学或学术上感兴趣的目标分子的合成方面的要点。为了造福公众 健康，我们已经与Samuel Deanmeade医学博士(JHU Med.)建立了合作关系。合成对苯二酚 开发一种新的、敏感的前列腺特异性抗原(PSA)检测方法。PSA是前列腺癌的标志物 癌症，其测量可能有助于疾病的诊断。

The specific aims and long-term objectives of this proposal are to use heterocumulenes (ketenes, ketenimines, and their synthetic equivalents) for new applications in asymmetric catalysis, namely the asymmetric synthesis of p-lactams (especially the trans diastereomers), catalytic asymmetric halogenation (chlorination, bromination and iodination), and catalytic asymmetric a-nitration. We also propose the development of new bifunctionally (Lewis acid-chiral nucleophile) catalyzed asymmetric reactions, including [2+2] as well as [4+2]cycloadditions of ketene enolates. All the chiral, optically enriched products of our reactions are meant to be either pharmacologically active, or to represent key intermediates and branch points in the synthesis of medicinally or academically interesting target molecules. In order to benefit public health, we have established a collaboration with Dr. Samuel Deanmeade, M.D. (JHU Med.) to synthesize p- lactams to develop a new, sensitive test for prostate specific antigen (PSA). PSA is a marker for prostate cancer, and its measurement may be useful to facilitate diagnosis of the disease.