SYNTHESIS OF CHLOROPEPTINS, GP120 CD4 BINDING INHIBITORS

在与北里研究所（日本）的同事合作下，我们最近确定了氯肽I和II的完整相对和绝对立体化学。 这些新的大双环七肽抑制HIV gp 120包膜糖蛋白与T细胞淋巴细胞簇决定簇4（CD 4）受体的结合，这是HIV感染中导致AIDS发作的关键事件。 gp 120-CD 4结合的抑制剂作为抗HIV治疗剂具有相当大的前景。 本研究计划的主要目标是：（A）设计一种有效的、立体控制的氯肽I全合成方法，重点是独特的轴向手性联芳基键的非对映选择性结构;和（B）设计、合成和测试氯肽类似物，以优化对gp-120-CD 4结合的抑制。

In collaboration with colleagues at the Kitasato Institute (Japan), we recently determined the complete relative and absolute stereochemistry of chloropeptins I and II. These novel macrobicyclic heptapeptides inhibit the binding of the HIV gp120 envelope glycoprotein to the cluster determinant 4 (CD4) receptor of T-cell lymphocytes, a critical event in HIV infection leading to the onset of AIDS. Inhibitors of gp120-CD4 binding hold considerable promise an anti-HIV therapeutic agents. The principal goals of this research program are: (A) to devise an efficient, stereocontrolled total synthesis of chloropeptin I, focusing on atrodiastereoselectiove construction of the unique, axially chiral biaryl linkage; and (B) to design, synthesize, and test analogs of the chloropeptins in order to optimize the inhibition of gp-120-CD4 binding.