Asymmetric Synthesis with Strained Molceules

描述（由申请人提供）：有机合成新反应的开发是健康相关领域的核心，如药物发现，过程化学，天然产物合成和生物学启发的分子设计。虽然目前的技术水平是这样的，只要有足够的时间和熟练的人员，就可以合成非常复杂的分子，但仍然需要串联反应，将简单的伙伴偶联起来，有选择地生产复杂的产物。

DESCRIPTION (provided by applicant): The development of new reactions for organic synthesis is at the core of health related fields such as drug discovery, process chemistry, natural products synthesis and biologically inspired molecular design. While the state of the art is such that remarkably complex molecules can be synthesized given ample time and skilled personnel, there persists a need for tandem reactions that couple simple partners to selectively produce complex products. The goal of this research program is to harness the unusual reactivity of high strain molecules to quickly generate molecules that are rich in stereochemical complexity and structural diversity. These 'strain assisted' reactions include directed nucleophilic addition/capture sequences and cycloaddition reactions of cyclopropenes and bicyclobutanes. In order for the methodology to have broad utility, it is explicitly necessary to develop asymmetric and enantioselective syntheses and reactions. While the exploratory stages of any program in synthetic methodology rely on screening, the refinement stage of each method will rely heavily on mechanistic analysis. The applications of this research are threefold: 1) the development of new synthetic methods that will have broad utility because they address fundamental, unsolved problems; 2) the development of unnatural amino acids with applications in environmentally responsive biomaterials; 3) the use of strained molecules in the syntheses of alkaloids with all-carbon quaternary centers and in the synthesis of pycnocomolide - a 12-deoxy-16-hydroxyphorbol natural product that is a potent activator of PKC and a target as a cancer drug. The syntheses of computationally designed pycnocomolide analogs are also proposed.