ALLENES OF SYNTHETIC AND BIOCHEMICAL IMPORTANCE

Buynak博士最近开发了一种合成方法学， 与以前未知的6-亚乙基苯丙胺的制备有关 合成了几种具有较强生物活性的化合物。 头孢菌素酶和弹性蛋白酶的抑制剂已经被发现。B-- 内酰胺酶抑制剂被用来治疗快速增殖的 细菌感染中青霉素耐药菌株的数量。白细胞 弹性蛋白酶在肺气肿患者和慢性阻塞性肺病患者中过度活跃 类风湿关节炎。对这些抑制剂的机理研究是 建议。一项综合调查将确定性质和 理想生物所需的烯丙基取代基的立体化学 活动。能够穿透细胞壁的衍生物将是 准备好了。末端(氨基烷基)亚乙基衍生物建议如下 符合这些标准的目标。头孢菌素类似物 阿伦人会做好准备。头孢菌素骨架胜运剂 额外的稳定性和骨骼相对平坦的地形 将扩大易受抑制的酶的范围。 新的抑制剂，涉及Penam核的元素取代， 都会做好准备。这些材料将有助于确定内酰胺酶 机制。在一项合成研究中，新的分子内加成 本课程将探讨烯的反应。这些反应预计将 产生理论上重要的三亚甲基甲烷作为中间体。 金属稳定的三亚甲基甲烷将从 相应的卡宾类化合物，以确定其合成用途。

Dr. Buynak has recently developed synthetic methodology leading to the preparation of the previously unknown 6-vinylidenepenams and has prepared several compounds which exhibit potent biological activity. Inhibitors of cephalosporinase and of elastase have been discovered. b-- Lactamase inhibitors are used in treating the rapidly proliferating number of penicillin-resistant strains of bacterial infection. Leukocyte elastase is overactive in patients with emphysema and in those with rheumatoid arthritis. A mechanistic study of these inhibitors is proposed. A synthetic investigation will determine the nature and stereochemistry of allenyl substituents necessary for optimal biological activity. Derivatives which can penetrate the cell wall will be prepared. Terminal (aminoalkyl)vinylidene derivatives are proposed as targets which fulfill these criteria. Cephalosporin analogs of the allenes will be prepared. The cephalosporin skeleton win convey additional stability and the relatively flat topography of the skeleton will broaden the scope of enzymes which are susceptible to inhibition. New inhibitors, involving elemental substitution of the penam nucleus, will be prepared. These materials will help define the lactamase mechanism. In a synthetic investigation, new intramolecular addition reactions of allenes will be explored. These reactions are expected to generate theoretically important trimethylenemethanes as intermediates. Metal-stabilized trimethylenemethanes will be prepared from the corresponding carbenoids to determine their synthetic utility.