PORPHYRIN SYNTHETIC METHODS FOR BIOORGANIC APPLICATIONS

用于生物有机应用的卟啉合成方法

• 批准号: 2734539
• 负责人: JONATHAN SIDNEY LINDSEY
• 金额: $ 23.21万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-12-01 至 1999-12-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2734539
• 关键词: chemical condensation; chemical models; chemical substitution; chemical synthesis; chlorin; electron spin resonance spectroscopy; heme; magnesium; phthalocyanin; porphyrins; pyrroles; tautomer; thermodynamics

The molecules comprising the porphyrin family are the most versatile prosthetic groups in nature. Shuttling electrons in respiration, binding and transporting oxygen, and serving in the active sites of diverse redox enzymes and electron transport chains are only a few of the prominent activities of porphyrinic molecules. Porphyrins work in concert with a diverse array of other molecules, and synthetic model systems of porphyrin- mediated processes enable the molecular interactions to be probed and identified with exacting precision. Our long-term goals are to prepare synthetic porphyrin model systems and to gain deep insight into porphyrin- mediated biological processes. To achieve this goal requires the ability to construct systems having 3-dimensional order incorporating porphyrinic and accessory molecules. Our specific aims are to; 1). Investigate, refine, and broaden the scope of the high concentration aerobic porphyrin synthesis, in order to achieve an eclectic synthetic method with the simplicity and preparative-scale of the Adler method and the milk conditions and scope of the room temperature synthesis. 2) Develop a set of synthetic methods for preparing porphyrins bearing four different meso-substituents (ABCD-porphyrins). This methodology will provide detailed architectural control of the local porphyrin environment and enable study of phenomena mediated by porphyrins in conjunction with collections of other molecules, such as in electron transport chains. 3) Develop simple and rational routes with capabilities for meso- substitution in the spectrum of hydroporphyrins, such as chlorins, bacteriochlorins, isobacteriochlorins, corroles, and ultimately corphins. The methodology will lead to model studies of naturally occurring hydroporphyrins such as green hemes, sirohemss, F430 and ultimately vitamin B12, and enable fundamental studies of hydroporphyrin tautomerization. These routes will make versatile models of reduced porphyrins nearly as accessible as porphyrin model systems are now. 4) Investigate the generality of our new mild synthesis of magnesium porphyrins, extend it to natural and synthetic hydroporphyrins, and determine the thermodynamic stability of magnesium chelates of a spectrum of porphyrins and hydroporphyrins. Taken together these studies will lead to a general advancement in the state of the art of model systems of porphyrinic compounds and deepen our understanding of the fundamental chemistry and functional versatility of the essential and fascinating family of tetrapyrrolic macrocycles.

构成卟啉家族的分子是最通用的 自然界中的假肢群。 电子在呼吸、结合中穿梭 运输氧气，并服务于多种氧化还原活性位点 酶和电子传递链只是其中几个突出的 卟啉分子的活性。 卟啉与 各种其他分子以及卟啉的合成模型系统 介导的过程使得分子相互作用能够被探测和 以严格的精度进行识别。 我们的长期目标是做好准备 合成卟啉模型系统并深入了解卟啉- 介导的生物过程。 要实现这个目标需要有能力 构建具有 3 维有序的包含卟啉的系统 和辅助分子。 我们的具体目标是； 1）。 排查、细化、拓宽高集中范围 有氧卟啉合成，以实现折衷合成 具有阿德勒方法的简单性和制备规模的方法 室温合成乳的条件和范围。 2）开发出一套制备卟啉轴承的合成方法 四种不同的内消旋取代基（ABCD-卟啉）。 该方法将 提供局部卟啉环境的详细架构控制 并能够研究卟啉介导的现象 其他分子的集合，例如电子传输链中的分子。 3）开发具有细观能力的简单合理的路线 氢卟啉谱中的取代，例如二氢卟酚， 菌绿素、异菌绿素、corroles 以及最终的corphins。 该方法将导致自然发生的模型研究 氢卟啉，例如绿血红素、sirohemss、F430 和最终的维生素 B12，并能够进行氢卟啉互变异构的基础研究。 这些路线将使还原卟啉的多功能模型几乎与 现在可以像卟啉模型系统一样访问。 4) 研究我们新的镁温和合成方法的通用性 卟啉，将其扩展到天然和合成的氢卟啉，以及 确定光谱中镁螯合物的热力学稳定性 卟啉和氢卟啉。 总的来说，这些研究将导致该领域的普遍进步。 卟啉化合物模型系统的最新技术并加深我们的研究 了解基本化学和功能多样性 四吡咯大环化合物的重要且迷人的家族。