Method of peptide synthesis

Throughout history, chemical synthesis of most of the work is done through the manual way, although the automation in the field of chemical is not new, such as peptides, automatic synthesis of oligonucleotides, current chemical and high-throughput screening, but this automated synthesis are limited to a single type of chemical reaction or process, there is no can cover all digital automation standard of synthetic organic chemistry and general chemical operation programming language.

A new paper published on November 26th in Science, one of the world's leading journals, reports the pioneering work of researchers at the university of Glasgow: the synthesis of important drug molecules in a reasonably priced modular chemical robot system called a Chemputer, or chemical computer.

Professor Lee Cronin, director of Regius chemistry department at the university of Glasgow, designed and developed this decision-making automation program, which can train chemists to rely on vision to complete tasks related to molecular assembly by using conductance sensors. The efficiency of this sensor can surpass human vision.The automation process is implemented in a modular robotic platform that runs a chemical programming language to control the assembly of related molecules.Moreover, even users with no programming knowledge can easily code.As long as Chemputer has the necessary modules and drivers, users can run published composite methods without reconfiguration.Chemputer includes software and physical equipment: bottled reagents, round-bottled flasks, filtration and liquid-liquid separation devices, rotary evaporators, and pipelines, valves, and pumps that carry chemicals.

Using this programmed automated synthesis system, the researchers produced three high-quality pharmaceutical compounds without any human intervention: diphenhydramine hydrochloride, rufiamide and sildenafil, with yields and purity comparable to those of synthetic compounds.Diphenhydramine hydrochloride is an antihistamine and mild sleep aid that requires a four-step sequence of synthesis starting with the grignard reaction.Rufinamide, a triazole derivative, is an anticonvulsant for the treatment of various epilepsy, and its synthesis is a relatively simple automated process.Sildenafil is a blockbuster erectile dysfunction drug commonly known as viagra.The authors show that the synthesis of all three compounds can be translated into computer code that can be transferred flexibly from platform to platform, greatly enhancing the reproducibility and reliable acquisition of complex molecules.

Professor Cronin said in an interview that the goal of his lab was that organic chemists would no longer have to do the usual synthesis by themselves, but would instead focus entirely on finding new reactions.To do this, he plans to build an open source database of synthetic programs Chemputer can understand that chemists can access at any time.Cronin also thinks Chemputer could make synthesis safer by keeping chemists out of the lab and by helping researchers minimize the use of solvents.

Nicola LB Pohl, a professor at indiana university in bloomington who is also developing automated software, says Chemputer's success is in ensuring that other chemists can easily learn and use Cronin's software.Professor Cronin has provided his code, which in the future will allow more synthetic chemists to think about how to automate their reactions.