Conformation, Automation and Applications of Polyborons in Synthesis

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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.