Conformation, Automation and Applications of Polyborons in Synthesis

有机合成是困难的，因为化学结构千变万化，再加上生成C-C键的挑战。这就是为什么有机合成的自动化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酸酯同系化能够在各种环境中以高度可靠的方式形成C-C键。为了将这一可靠的方法转移到自动化平台上，我们需要一种方法来在同系物之间提纯硼酸酯，并考虑使用附着在硼酸酯上的含有胺的二醇来实现捕捉和释放协议。在同源后，硼酸酯将被捕获在酸性树脂上，然后用胺洗脱后释放。我们将探索将这种自动合成应用于使用各种构建块的日益复杂的自然产品。除了硼酸酯同系化，还将进行硼氢化和二硼化，以使更广泛的天然产品得以生产。我们将针对那些结构被错误分配的化合物，在那里可以使用自动化来制造不同的异构体来识别正确的结构。我们将探索聚硼酸酯的自动化合成，并研究硼酸酯取代基如何控制柔性碳链的构象。例如，1，3-聚硼酸酯有望形成线形和螺旋形，这取决于它们的立体化学。胺与硼酸和酯有很强的结合力，因此在聚硼酸酯中加入互补的多胺应该会形成β-折叠和双链螺旋。我们将利用氮和硼之间的络合作用来构建一种新的密码子语言，以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成寡聚肽序列。

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.