Asymmetric Synthesis of Nitrogen Heterocycles

描述（由申请人提供）：现代药物发现要求快速和模块化组装日益复杂的物质。与医学相关的分子绝大多数具有氮功能，前200名品牌药物中有179种含有至少一个n原子。越来越多地，氮原子不仅仅是一个功能取代基，如一个垂胺或连接酰胺，而是以杂环的形式存在，通常带有立体中心。开发从易于获取的前体获取这些杂环化合物的方法是一个有吸引力的目标。由此产生的杂环将促进药物发现的步伐，从抗生素、抗抑郁药以及蛋白质-蛋白质相互作用的激动剂和拮抗剂（如Hsp40-Hsp70）的生物活性药物中可以看到共同的基序。本研究的具体目标如下：1)建立[2+2+2]环加的临时系缚策略；2)研究酰胺与烯烃/炔的氧化偶联？通过催化/氧化协议组装哌啶的系统；3)利用金属催化[4+2]反应中容易获得的氮杂二烯；4)实施异氰酸酯环添加，涉及烯和乙烯基环丙烷。这门科学的长期影响是使化学家能够快速高效地组装复杂的结构。

DESCRIPTION (provided by applicant): Modern drug discovery mandates the rapid and modular assembly of increasingly complex substances. Medicinally relevant molecules overwhelmingly bear nitrogen functionality with 179 of the top 200 brand name drugs containing at least one N-atom. Increasingly, the nitrogen atom is not merely a functional substituent, such as a pendant amine or linking amide, but is present in the form of a heterocycle, often bearing stereocenters. The development of methods to access these heterocycles from easily accessible precursors is an attractive goal. The resultant heterocycles will facilitate the pace of drug discovery, with the common motifs visible in biologically active agents ranging from antibiotics, antidepressants as well as agonists and antagonists of protein-protein interactions such as Hsp40-Hsp70. The specific goals of this research are as follows: 1) develop temporary tethering strategies for [2+2+2] cycloadditions; 2) Investigate the oxidative coupling of amides and alkene/alkyne ? systems to assemble piperidines by a catalyzed/oxidative protocol; 3) Exploit readily available aza-dienes in metal-catalyzed [4+2] reactions; and 4) Implement isocyanate cycloadditions to involve allenes and vinyl cyclopropanes. The long-term impact of this science is to enable chemists to rapidly assemble complex structures with high efficiency.