Heterocumulenes in Asymmetric Catalysis

描述(由申请人提供)：本提案的具体目标和长期目标是使用杂聚烯(酮、酮亚胺及其合成等价物)在不对称催化中的新应用，即不对称合成β-内酰胺(特别是反式非对映异构体)、催化不对称卤化(氯化、溴化和碘化)和催化不对称α-硝化。我们还建议开发新的双功能(Lewis酸-手性亲核试剂)催化的不对称反应，包括[2+2]和[4+2]烯醇酸酯的环加成反应。我们反应的所有手性、光学富集物要么具有药理活性，要么代表医学或学术上感兴趣的目标分子合成中的关键中间体和分支点。为了惠及公众健康，我们与医学博士Samuel Deanmeade(JHU Med.)建立了合作关系。目的：合成β-内酰胺类抗生素，以开发一种新的、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，其测量可能有助于前列腺癌的诊断。

DESCRIPTION (provided by applicant): 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 beta-lactams (especially the trans diastereomers), catalytic asymmetric halogenation (chlorination, bromination and iodination), and catalytic asymmetric alpha-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 beta-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.