SYNTHESIS & SYNTHETIC UTILITY OF 1-ACYLDIHYDROPYRIDINES

本建议描述了合成各种取代的 1-酰基二氢吡啶及其作为合成中间体的用途。 用于区域特异性制备各种卤代取代的 1-将探索酰基二氢吡啶。 一旦准备好，光环 取代基将用于进一步阐述二氢吡啶 戒指 取代基在分子上的各种区域特异性加成 将研究二氢吡啶环。 这将包括Vilsmeier 乙酰化和酰化，Friedel-Crafts酰化和Grignard 由β-三丁基甲锡烷基引导的对1-酰基吡啶鎓盐的加成 组 β-三丁基锡烷基二氢吡啶将提供 通过区域特异性有机锡的几种其它取代的二氢吡啶 化学. 区域特异性取代的所有位置的 将研究二氢吡啶环。 这将有助于开发 取代吡啶的芳构化新合成 二氢吡啶中间体。 除了区域特异性合成之外， 取代的吡啶，提出的二氢吡啶化学将是 用于合成各种吲嗪和喹嗪生物碱。 的 吲哚里西啶和喹里西啶生物碱已经成为许多 生物和化学研究。 这些生物碱中有几种是强效的 可以调节各种正常和异常的生长 哺乳动物组织 提出的二氢吡啶化学应提供 实际进入合成这些有趣的杂环 化合物.

This proposal describes a study of the synthesis of various substituted 1-acyldihydropyridines and their utility as synthetic intermediates. Methodology for the regiospecific preparation of various halosubstituted 1-acyldihydropyridines will be explored. Once prepared, the halo substituent will be utilized to further elaborate the dihydropyridine ring. Various regiospecific additions of substituents onto the dihydropyridine ring will be investigated. This will include Vilsmeier formylation and acylations, Friedel-Crafts acylations, and Grignard additions to 1-acylpyridinium salts directed by a Beta-tributylstannyl group. The Beta-tributylstannyldihydropyridines will provide access to several other substituted dihydropyridines via regiospecific organotin chemistry. Regiospecific substitution at all positions of the dihydropyridine ring will be studied. This will allow for development of novel syntheses of substituted pyridines through aromatization of the dihydropyridine intermediates. In addition to the regiospecific syntheses of substituted pyridines, the proposed dihydropyridine chemistry will be used to synthesize various indolizidine and quinolizidine alkaloids. The indolizidine and quinolizidine alkaloids have been subjects of numerous biological and chemical studies. Several of these alkaloids are powerful vesicants and can modulate the growth of various normal and abnormal mammalian tissues. The dihydropyridine chemistry proposed should provide a practical entry into the synthesis of these interesting heterocyclic compounds.