Conformation, Automation and Applications of Polyborons in Synthesis

聚硼的构象、自动化及其在合成中的应用

• 批准号: EP/Y028015/1
• 负责人: Varinder Aggarwal
• 金额: $ 269.78万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FY028015%2F1
• 关键词: Conformation; Automation; Applications; Polyborons; Synthesis

Organic synthesis is hard because of the myriad and variety of chemical structures coupled with the challenges of making C-C bonds. This is one of the reasons why automation of organic synthesis is also hard because many C-C bond forming reactions are sensitive to their environment. In recent years, we have discovered that reagent-controlled homologation of boronic esters enables C-C bond formation in a highly reliable way in a variety of settings. In order to transfer this robust methodology to an automated platform we need a method to purify the boronic ester between homologations and have considering using an amine containing diol attached to the boronic ester to enable a catch-and-release protocol. After homologation, the boronic ester would be caught on an acid resin and then released upon elution with an amine. We will explore the application of this automated synthesis to natural products of increasing complexity using a variety of building blocks. In addition to boronic ester homologation, hydroboration and diboration will be carried out to enable a broader set of natural products to be made. We will target compounds whose structure has been misassigned, where automation can be used to make different isomers to identify the correct structure. We will explore the automated synthesis of polyboronic esters and investigate how the boronic ester substituents can control the conformation of flexible carbon chains. For example, 1,3-polyboronic esters are expected to form linear and helical shapes depending on their stereochemistry. Amines bind strongly to boronic acids and esters and so addition of complementary polyamines to the polyboronic esters should result in the formation of beta sheets and double stranded helices. We will use the complexation between nitrogen and boron to build a new codon language to create molecules for information storage and retrieval, which will enable the translation of a pseudo genetic code to an oligomeric peptide-like sequence.

有机合成很困难，因为化学结构千变万化，再加上制造碳碳键的挑战。这也是为什么自动化有机合成也很困难的原因之一，因为许多C-C键形成反应对环境很敏感。近年来，我们发现试剂控制的硼酯同源性使C-C键形成在各种设置中以高度可靠的方式。为了将这种强大的方法转移到自动化平台，我们需要一种方法来纯化同源物之间的硼酯，并考虑使用含有二醇的胺附着在硼酯上，以实现捕获和释放协议。经过鉴定后，硼酯将被酸性树脂捕获，然后用胺洗脱释放。我们将探索使用各种构建块将这种自动合成应用于日益复杂的天然产物。除了硼酯同源性外，还将进行氢硼化和脱硼化，以使更广泛的天然产物得以制造。我们将针对那些结构被错误分配的化合物，在那里自动化可以用来制造不同的异构体来识别正确的结构。我们将探索聚硼酯的自动合成，并研究硼酯取代基如何控制柔性碳链的构象。例如，1,3-聚硼酯根据其立体化学性质可以形成线性和螺旋形状。胺与硼酸和酯结合强烈，因此在聚硼酯上添加互补多胺会形成-片和双链螺旋。我们将利用氮和硼之间的络合作用构建一种新的密码子语言来创建用于信息存储和检索的分子，这将使伪遗传密码能够翻译为寡聚肽样序列。