Asymmetric Synthesis of Biologically Active Materials

描述：（申请人的描述）我们在任期内的主要目标 该补助金将用于开发新的催化有机反应， C-C键的立体定向组装在合成中具有广泛的应用 具有药理活性的多种目标化合物。的 正在开发的反应技术专门设计用于解决 基本的C-C键形成反应，通常适用于复杂的 分子合成和重要化学构件的制备 工业或医药化学合成活动的背景。 我们研究了催化的不对称酰氯-醛环缩合反应， 实验室进一步发展为通用反应技术， 不对称有机合成这一方法将在2004年得到完善和发展。 全合成天然材料的背景， 表达有效的抗癌和抗病毒活性，包括两性霉素B B， rhazinilam和motuporin。此外，一个家族的独特的光学活性 Al（III）基刘易斯酸将被开发为双官能刘易斯酸-刘易斯酸 应用于各种不对称C-C键的碱性催化剂 建筑。一种经济和操作简单的合成高度 对映体富集的β-氨基酸也被有效地利用， β-肽的合成及环肽的制备 β-肽结构设计作为整联蛋白受体拮抗剂。

DESCRIPTION: (Applicant's Description) Our principle goal during the tenure of this grant will be the development of new catalyzed organic reactions for the stereospecific assemblage of C-C bond with broad, applications to the synthesis of a variety of target compounds possessing pharmacological activity. The reaction technology under development is specifically designed to address fundamental C-C bond forming reactions that are generally applicable to complex molecule synthesis and the preparation of important chemical building blocks in the context of industrial or medicinal chemistry synthesis activities. Catalyzed asymmetric acyl chloride-aldehyde cyclocondensations developed in our laboratories are further developed as versatile reaction technology for asymmetric organic synthesis. This methodology will be refined and developed in the context of the total synthesis of naturally occurring materials that express potent anticancer and antiviral activities, including amphidinolide B, rhazinilam, and motuporin. Moreover, a family of unique optically active Al(III)-based Lewis acids will be developed as bifunctional Lewis acidic-Lewis basic catalysts with applications to a variety of asymmetric C-C bond constructions. An economical and operationally simple synthesis of highly enantiomerically enriched beta-amino acids is also exploited in an efficient approach to the synthesis of beta-peptides and the preparation of cyclic beta-peptide structures designed to function as integrin receptor antagonists.