ASYMMETRIC SYNTHESIS OF NON-PROTEIN AMINO ACIDS

我们的最终目标是开发和建立新的、高效的和可靠的 合成各种非蛋白质氨基酸和蛋白质的新方法 相关化合物与立体化学的完美控制。那些 方法学对生物多样性的研究是非常有益的。 对非蛋白质氨基酸和相关化合物的作用不能 通过从自然来源中分离而获得足够数量的。作为一名 为实现这一具有挑战性的目标，我们将发起和推动 非蛋白质氨基酸不对称合成的研究进展 相关化合物通过应用“β-内酰胺合成子法” 都是我们实验室研发出来的。这项拟议的研究有两个项目。 在项目(1)中，我们将开发有效的方法来解决不对称问题 α-取代α-氨基酸及其二肽的合成 高立体选择性的单烷基化、双烷基化和三烷基化的基础 β-内酰胺酯。一种新的4-羟甲基-β-内切酶的切割方法 将对内酰胺类药物进行检查，并使用可回收的新的烯烃和烯醇类化合物 将开发手性助剂。在项目(2)中，我们将探索 一种新的高效的非蛋白质氨基酸及其合成途径 通过高度立体选择性的官能化和 对映体纯3-氨基-4-烯基-β-内酰胺的转化。 我们将开发各种新的不对称有机转换 这个项目的进程。这些非蛋白质氨基酸及其 由此获得的衍生品将提供天然生成的 抗生素及其类似物，植物代谢物，酶抑制剂， 碳水化合物，以及有用的多肽激素类似物和 手性大环。我们将应用新版本的“beta-Lactam Synthon (I)神经节苷脂神经酰胺的不对称合成 它们是与细胞膜有关的重要糖苷脂。 脑细胞和脊椎动物细胞和(II)(R，S)-和(R，R)-3-氯-4- 羟基苯丝氨酸是万古霉素的重要成分。

Our ultimate goal is to develop and establish new, efficient and reliable new methodologies for the synthesis of various non-protein amino acids and related compounds with perfect control of stereochemistry. Those methodologies are very beneficial for the investigation of the biological functions on non-protein amino acids and related compounds which cannot be obtained in sufficient quantity by isolation from natural sources. As a fundamental approach to this challenging goal, we will initiate and promote the research on the asymmetric synthesis of non-protein amino acids and related compounds by applying the "beta-Lactam Synthon Method" which has been developed in our laboratory. The proposed research has two projects. In the project (1), we will develop effective methods for the asymmetric synthesis of alpha-substituted alpha-amino acids and their dipeptides on the basis of highly stereoselective mono-, double-and triple alkylations of beta-lactam esters. A new cleavage methods via 4-hydroxymethyl-beta- lactams will be examined, and new ketenes and enolates with recyclable chiral auxiliaries will be developed. In the Project (2), we will explore new and efficient routes to a variety of non-protein amino acids and their derivatives through highly stereoselective functionalizations and transformations of enantiomerically pure 3-amino-4-alkenyl-beta-lactams. We will develop various new asymmetric organic transformations during the course of this project. Those non-protein amino acids and their derivatives, thus obtained, will furnish components of naturally occurring antibiotics and their analogues, plant metabolites, enzyme inhibitors, carbohydrates, and useful building blocks of peptide hormone analogues and chiral macrocycles. We will apply the new version of "beta-Lactam Synthon Method" to the asymmetric synthesis of (i) the ceramide of gangliosides which are important glycoshingolipids associated with membranes in the brain and vertebrate cells, and (ii) (R,S)- and (R,R)-3-chloro-4- hydroxyphenylserines which are important components of vancomycinic acid.