ALLENES OF SYNTHETIC AND BIOCHEMICAL IMPORTANCE

Buynak博士最近开发了一种合成方法， 用于制备以前未知的6-亚乙烯基青霉烯， 制备了几种表现出有效生物活性的化合物。 已经发现了头孢菌素酶和弹性蛋白酶的抑制剂。B-- 内酰胺酶抑制剂用于治疗快速增殖的 细菌感染的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 类风湿关节炎 这些抑制剂的机理研究是 提出了综合调查将确定性质和 最佳生物活性所需丙二烯基取代基的立体化学 活动 可以穿透细胞壁的衍生物将被 制备 末端（氨基烷基）亚乙烯基衍生物被提议为 满足这些标准的目标。 头孢菌素类似物 将制备丙二烯。 头孢菌素骨架赢得输送 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，涉及元素取代的青霉烷核， 会做好准备。 这些材料将有助于确定内酰胺酶 机制 在合成研究中，新的分子内加成 将探索联烯的反应。 预计这些反应将 产生理论上重要的三亚甲基甲烷作为中间体。 金属稳定化的三亚甲基甲烷将由 相应的类卡宾以确定它们的合成效用。

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.