ANALOGS AND BIOISOSTERES OF PYRROLIZIDINE ALKALOIDS

最近我们开发了对映异构体的反应。 取代3-吡咯烷酮对映体(镜像)的合成 内酰胺类药物。适当地替代-β-内酰胺类药物可以转化为 以立体专一性的方式合成各种光学纯净的生物碱 类型。我们建议进一步发展这些合成方法和 合成多种吡咯里西丁生物碱(天然存在 以及那些在自然界中不为人所知的物种)。 还将合成一些相关的吲哚里西定和 喹诺利定衍生物以及其中的吡咯里西定类似物 其中一个环碳已被杂原子取代。 已知有几种吡咯里西丁生物碱是致癌物质。一些人 这些物质通过污染进入我们的食物链 谷物或草药和茶。家畜被感染了 通过食用含有吡咯里西丁的饲料植物 生物碱。牛奶和蜂蜜有时是这些的携带者 生物碱。已发现半合成的吡咯里西丁碱 具有广泛的生物活性。手性吡咯里西酮 碱及其氮杂、氧杂或这类类似物和其他生物碱 由我们准备的将进行一系列生物活性测试 被一家制药公司。一些手性合成 已开发的化合物有望具有更强的对映选择性或更简单 而不是文献中的替代合成方法。

Recently we have developed enantiospecific reactions for the synthesis of antipode (mirror image form) of substituted 3- lactams. Appropriately substitute-beta-lactams can be converted in stereospecific fashion to optically pure alkaloids of various types. We propose to further develop these synthetic methods and synthesize a variety of pyrrolizidine alkaloids (naturally occurring as well as those not known in nature) in both antipodal forms. Also to be synthesized are some related indolizidine and quinolizidine derviations as well as pyrrolizidine analogs in which one of the ring carbons has been replaced by a hetero atom. Several pyrrolizidine alkaloids are known to be carcinogens. Some of these substances enter our food chain through contaminated grains or herbal medicines and teas. Livestocks are infected through the consumption of forage plants containing pyrrolizidine alkaloids. Cow's milk and honey are sometimes carriers of these alkaloids. Semisynthetic pyrrolizidine bases have been found to possess a wide variety of biological activity. Chiral pyrrolizidine bases and their aza-, oxa- or this-analogs and other alkaloids prepared by us would be tested for a range of biological activity by a pharmaceutical company. Some of the chiral syntheses developed are expected to be more enantioselective or simpler than the alternative syntheses in the literature.