Chemists are building a molecular version of Lego that snaps carbon chains together automatically, using boronic esters as the universal connector pieces. The problem is that making carbon-carbon bonds—the backbone of almost every organic molecule—is notoriously unreliable and sensitive to reaction conditions. This has made automating organic synthesis extremely difficult. The researchers have discovered that boronic esters can form carbon-carbon bonds with exceptional reliability, but automating the process requires a way to purify the esters between each reaction step. They plan to use a "catch-and-release" system: an amine-containing diol grabs the boronic ester onto an acid resin, then releases it when washed with an amine. If successful, this automated platform could rapidly synthesise natural products whose chemical structures have been misassigned, making multiple isomers to identify the correct one. The project also explores fundamental science: polyboronic esters can form linear or helical shapes depending on their stereochemistry, and adding polyamines should create beta sheets and double-stranded helices. Most ambitiously, the researchers aim to use nitrogen-boron binding as a new "codon language" for information storage, translating a pseudo-genetic code into oligomeric peptide-like sequences. This is primarily curiosity-driven fundamental research with no immediate practical application, though automated synthesis of complex molecules could eventually transform pharmaceutical manufacturing.
View original technical description
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.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know