Carbon-Carbon Bond-Formation via Thioacetals (Chemistry)

氨基酸是蛋白质的组成部分，因此它们及其化学在生物化学中占有重要地位。大自然能够以一种高度特定的方式高效地制造氨基酸，因为它使用了酶。然而，许多潜在用途的氨基酸不是自然合成的，因此化学家需要工具来使这些化合物具有与自然界中发现的相同的特异性。有机化学和高分子化学计划中的这个项目正在开发这样的反应，化学界将对此大有裨益。本研究的总体目标是开发基于亲电甘氨酸衍生模板的碳-碳键结构的不对称合成α-氨基酸的高效实用方法。此外，还将研究这些甘氨酸模板的自由基偶联和电环偶联。在实际应用方面，获得高光学纯度和化学纯度的D-或L构型的氨基酸将是这项研究的主要用途。这些选择性偶联反应将通过仔细研究半氨基缩醛的基础化学来实现，半氨基缩醛作为阳离子和自由基与各种有机金属试剂反应的底物。发现了一种新的有机锡乙酰基偶联反应，并将作为制备具有较强生物活性的乙烯基和炔基α-氨基酸的方法进行研究。将研究几种第二代手性助剂，以扩大亲电甘氨酸模板概念的范围。新的方法学将通过几种具有代表性的复杂氨基酸的全合成来展示。

Amino acids are the building blocks of proteins, and thus they, and their chemistry, occupy an important position in biochemistry. Nature is able to efficiently make amino acids in a highly specific fashion because it employs enzymes. However, many amino acids of potential use are not synthesized by nature, and so the chemist is in need of tools to make these compounds with the same specificity as found in nature. This project in the Organic and Macromolecular Chemistry Program is developing such reactions for which the chemistry community will have great use. The overall objective of the proposed research is to develop efficient and practical methodology for the asymmetric synthesis of alpha-amino acids based on carbon-carbon bond constructions of electrophilic glycine-derived templates. In addition, the free radical and electrocyclic couplings to these glycine-templates will be investigated. On the practical side, access to either D- or L- configured amino acids in high optical purity and chemical purity will be the primary utility of this research. These selective coupling reactions will be achieved by a careful study of the fundamental chemistry of hemi-amino acetals as substrates for cationic and radical reactions with a variety of organometallic reagents. A new organotin acetylide coupling reaction has been discovered and will be investigated as a means for preparing vinyl and alkynyl alpha-amino acids which have potent biological activities. Several second-generation chiral auxilliaries will be investigated to broaden the scope of the electrophilic glycine template concept. The new methodology will be demonstrated with total syntheses of several representative, complex amino acids.