SYNTHETIC STUDIES OF USTILOXIN A

具有干扰细胞中微管介导功能的化合物作为治疗剂、探测细胞机制的工具、合成靶点等近来引起了人们的兴趣。紫杉醇等化合物在化疗方案中的成功应用，说明了能够阻断微管细胞作用的细胞毒性药物的医学重要性。Ustiloxin A是这类化合物的新成员，它提出了一些有趣的合成挑战。本研究的目标是完成ustiloxin a的全合成。这样，这种独特的13元环肽的合成将解决一些有趣的键结构问题。第一个是利用连续的不对称烷基化和还原序列合成叔-芳基- α -氨基酸。要解决的第二个挑战是通过不对称甘氨酸酰胺醛醇与必要的醛缩合来构建-羟基- α -氨基酸。本提案的目的将是概述一个简明的合成计划，以氧合α -氨基酸和应用这些建议的方法，以合成乌斯蒂洛素a。

DESCRIPTION Compounds having the ability to interfere with microtubule mediated functions in the cell have become of recent interest as therapeutic agents, tools to probe the machinery of the cell,, as synthetic targets. The successful use of compounds in chemotherapeutic regiments, like Taxol, illustrate the medical importance of cytotoxic agents capable of interrupting the cellular role of microtubules. Ustiloxin A is a new member of this class of compounds that presents some interesting synthetic challenges. It is the goal of the proposed research to complete the total synthesis of ustiloxin A. In doing so, the synthesis of this unique 13 membered cyclic peptide will address some interesting bond constructions. The first of which is the asymmetric synthesis of a tertiary beta-aryloxy-alpha-amino acid utilizing a sequential asymmetric alkylation and reduction sequence. The second challenge to be addressed is the construction of a beta-hydroxy-alpha-amino acid by the asymmetric glycinamide aldol condensation with the requisite aldehyde. The purpose of this proposal will be to outline a concise synthetic plan to oxygenated alpha-amino acids and apply those proposed methods to the synthesis of ustiloxin A.