SYNTHETIC STUDIES OF USTILOXIN A

描述具有干扰细胞中微管介导功能的能力的化合物作为治疗剂、探测细胞机械的工具、作为合成靶点最近已成为感兴趣的对象。化合物在化疗方案中的成功应用，如紫杉醇，说明了能够干扰微管细胞作用的细胞毒剂的医学重要性。Ustilooxin A是这类化合物中的新成员，它带来了一些有趣的合成挑战。这项研究的目标是完成Utilooxin 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。第一个是利用顺序的不对称烷基化和还原序列不对称合成叔基β-芳氧基-α-氨基酸。需要解决的第二个挑战是通过甘氨酰胺羟醛与必需的醛的不对称缩合来构建β-羟基-α-氨基酸。这项建议的目的是勾勒出一个简明的含氧α-氨基酸的合成计划，并将所提出的方法应用于Utilooxin A的合成。

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.