SYNTHESIS OF AMINO ACID-DERIVED NATURAL PRODUCTS

描述（由申请人提供）： 化学合成提供了生产化疗药物的能力，化学反应是从事药物发现过程的药物化学家不可替代的工具。化学反应技术的进步缩短了作为潜在候选药物的化学实体的概念与其合成用于随后的生物学评价之间的间隔。因此，合成活动是一个关键的学科，继续对医学和生物学领域产生重要影响。目前的拨款将继续致力于开发新的立体选择性反应，这些反应与从氨基酸成分合成抗生素和抗内毒素剂有关。处理新反应发现的方法学研究将强调用于合成复杂氨基酸的手性金属催化剂的开发。这些进展最终将导致β-羟基-α-氨基酸和α，β-二氨基酸的不对称合成的实际路线。与该项目相关的合成目标将包括抗病毒环状七肽cyclomarin A，海洋毒素azaspiracid 1和细胞毒性六环生物碱daphnicyclidin A。

DESCRIPTION (provided by applicant): Chemical synthesis provides the capacity to produce chemotherapeutic agents, and chemical reactions are the irreplaceable tools of the medicinal chemist engaged in the drug discovery process. Advances in chemical reaction technology reduce the interval between the conception of the chemical entity as a potential drug candidate and its synthesis for subsequent biological evaluation. As a consequence, the synthesis activity is a critical discipline that continues to have an important impact upon the fields of both medicine and biology. The present grant will continue to address the development of new stereoselective reactions which are relevant to the synthesis of antibiotic and antinepolastic agents derived from amino acid constituents. The methodological studies dealing with new reaction discovery will emphasize the development of chiral metal catalysts for the synthesis of complex amino acids. These advances should culminate in practical routes to the asymmetric synthesis of beta-hydroxy-alpha-amino acids and alpha, beta-diamino acids. Synthesis targets associated with this project will include the antiviral cyclic heptapeptide cyclomarin A, the marine toxin, azaspiracid 1, and the cytotoxic hexacyclic alkaloid daphnicyclidin A.