Photoassisted access to novel polyheterocyclic scaffolds with increased saturatio

我们将开发一种新的合成方法， 反应被并入多样性导向的分裂-合并组合合成中。 光化学反应为构建复杂的多环支架提供了无与伦比的前景。 它们为复杂的合成目标提供了许多合成捷径和简洁的途径。 然而，光化学从未成为合成化学家追求的工具， 高通量合成根本不存在。 具体来说，我们的目标是开发一种新的光辅助合成方法， 拓扑多样的N，O，S-多杂环，含有大部分sp3杂化 碳原子和立体中心，并被各种官能团修饰， 碳/杂环悬垂物刚性或半刚性地保持在独特的空间构型中， 这些新颖的核心框架具有最少数量的可旋转键。的合成策略 将涉及关键的光化学步骤及其与基态反应的结合， 我们最近发现的氮杂亚烷基的分子内环加成反应 通过激发态质子从酰氨基或氨基转移到羰基而光生 基团或亚胺。 在一系列功能内实现定义明确的三维关系 基团和/或杂环部分是合成药物化学的核心。广大 目的是通过系统地对化学品进行取样， 空间具有多样化的核心结构，并增加了一系列外围功能。 从高通量化学的观点来看，该任务只能用不同的组来实现。 独特的核心支架以独特的3D模式悬挂着各种功能性挂件。 高通量合成方法被指责为“将发现努力转向非手性， 芳香族化合物”，而天然产物，具有广泛的生物活性，看起来 不像sp2主导的芳族杂环。我们的光辅助合成 该方法将产生多种独特的（多）杂环核心支架，其含有高的 通过Lovering的Fsp 3饱和参数量化的饱和碳（即sp3）的数量。

We will develop a new synthetic methodology where high yielding photochemical key reactions are incorporated into a diversity-oriented split-and-pool combinatorial synthesis. Photochemical reactions hold unparalleled promise for building complex polycyclic scaffolds. They offer a number of synthetic shortcuts and concise pathways to complex synthetic targets. Yet, photochemistry never became a sought-after tool by synthetic chemists and its utilization in high-throughput synthesis is simply non-existent. Specifically, we aim to develop a new photoassisted synthetic methodology for rapid access to topologically diverse N,O,S-polyheterocycles, containing a large fraction of sp3 hybridized carbon atoms and stereogenic centers, and decorated by various functional groups and carbo/heterocyclic pendants rigidly or semi-rigidly held in a unique spatial configuration by these novel core frameworks with a minimal number of rotatable bonds. The synthetic strategy will involve key photochemical steps and their combination with ground state reactions, most prominently our recently discovered intramolecular cycloadditions of azaxylylenes photogenerated via excited state proton transfer from the amido or amino-group to the carbonyl group or imine. Achieving a well-defined three-dimensional relationship within an assortment of functional groups and/or heterocyclic moieties is central to synthetic medicinal chemistry. The broad objective is to generate potential pharmacophores by systematically sampling the chemical space with diversified core structures augmented with a range of peripheral functionalities. From the high throughput chemistry standpoint this task can only be achieved with a diverse set of distinctive core scaffolds suspending a variety of functional pendants in a unique 3D pattern. High throughput synthetic methods are blamed for "steering discovery efforts toward achiral, aromatic compounds" while natural products, possessing a broad spectrum of bioactivity, look nothing like the sp2-dominated aromatic heterocycles. Our photoassisted synthetic methodology will produce a variety of unique (poly)heterocyclic core scaffolds containing high number of saturated, i.e. sp3, carbons quantified by Lovering's Fsp3 saturation parameter.