ASYMMETRIC SYNTHESIS OF NON-PROTEIN AMINO ACIDS

我们的最终目标是开发和建立新的，高效和可靠的 合成各种非蛋白质氨基酸的新方法， 相关化合物与立体化学的完美控制。 那些 方法学对于生物学的研究是非常有益的。 对非蛋白质氨基酸和相关化合物的功能， 从自然资源中分离出足够数量的。 作为 为了实现这一具有挑战性的目标，我们将启动并促进 非蛋白质氨基酸的不对称合成研究， 通过应用“β-内酰胺合成子方法”， 是在我们的实验室里开发的。 该研究有两个项目。 在项目（1）中，我们将开发有效的方法， α-取代的α-氨基酸及其二肽的合成 高立体选择性的单-、双-和三烷基化的基础 β-内酰胺酯。 4-羟甲基-β- 内酰胺将被检查，新的烯酮和烯醇与可回收的 将开发手性助剂。 在项目（2）中，我们将探索 制备多种非蛋白质氨基酸及其衍生物的新的有效途径， 通过高度立体选择性官能化的衍生物， 对映体纯的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化过程中， 这个项目的过程。 这些非蛋白质氨基酸及其 衍生物，从而获得，将提供天然存在的组分， 抗生素及其类似物，植物代谢物，酶抑制剂， 碳水化合物和肽激素类似物的有用的结构单元， 手性大环 我们将应用新版本的“β-内酰胺合成子 方法”不对称合成（i）神经节苷脂的神经酰胺 它们是与细胞膜相关的重要糖鞘脂， 脑和脊椎动物细胞，和（ii）（R，S）-和（R，R）-3-氯-4- 羟苯基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.