ANALOGS AND BIOISOSTERES OF PYRROLIZIDINE ALKALOIDS

吡咯里西啶生物碱的类似物和生物电子等排体

• 批准号: 3438627
• 负责人: MAGHAR S MANHAS
• 金额: $ 4.38万
• 依托单位: STEVENS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-06-01 至 1990-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3438627
• 关键词: antineoplastics; beta lactam antibiotic; chemical carcinogenesis; chemical structure function; drug design /synthesis /production; indoles; monocrotaline; quinolizine; stereoisomer; steroids

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indolizidine and quinolizidine derviations as well as pyrrolizidine analogs in which one of the ring carbons has been replaced by a hetero atom.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.

最近我们开发了对映特异性反应 取代3-对映体（镜像形式）的合成 内酰胺。 可以适当地转化取代-β-内酰胺 以立体定向方式形成各种光学纯生物碱 类型。 我们建议进一步开发这些合成方法并 合成多种吡咯里西啶生物碱（天然存在 以及那些自然界中未知的）两种对映形式。 还需要合成一些相关的吲哚里西啶和 喹啉西啶衍生物以及吡咯西啶类似物，其中 其中一个环碳已被杂原子取代。 已知几种吡咯里西啶生物碱是致癌物质。 一些 这些物质通过受污染的途径进入我们的食物链 谷物或草药和茶。 牲畜被感染 通过食用含有吡咯里西啶的饲料植物 生物碱。 牛奶和蜂蜜有时是这些物质的载体 生物碱。 已发现半合成吡咯里西啶碱 具有多种生物活性。 手性吡咯里西啶 碱基及其氮杂、氧杂或此类似物以及其他生物碱 我们准备的产品将接受一系列生物活性测试 由一家制药公司。 一些手性合成 开发的预计将更具对映选择性或更简单 比文献中的替代合成。