Total synthesis of two antibiotics using a molybdenum catalyst
ChemSci Pick of the Week
In today’s pick, Maciej Walczak and his team from the University of Colorado, Boulder, describe a total synthesis of a series of thiopeptides – a class of potent antibiotics.
Total synthesis is the process of synthesising a complex molecule from small, readily-available starting molecules. It often refers to molecules that already exist in nature, so the total synthesis is in part an academic exercise in fundamental chemistry – but it can also lead to the discovery of new synthetic techniques that will be useful to chemists designing a variety of useful molecules.
Dr Walczak and his team describe the total synthesis of two thiopeptides that have antibiotic properties. They were first isolated from natural sources over 70 years ago. Now they have been synthesised from scratch using a new catalyst.
A key problem in the synthesis was how to create thiazoles – five-membered rings containing a sulphur atom and a nitrogen atom. They begin with a cysteine fragment, and convert it to a thiazole via a cyclodehydration reaction (creating a cyclic fragment and eliminating an H2O molecule in the process). This reaction often requires a stoichiometric reagent (a participating molecule that is used up during the reaction), but Dr Walczak and his team have used a molybdenum catalyst. This is less wasteful and more efficient than using a stoichiometric reagent, since only a small amount of catalyst is required – it can repeat the reaction multiple times and can be recovered at the end of the reaction.
The full synthesis uses 15 steps, and is a process of building up a long string of molecular fragments from small starting blocks. The only by-product is water, making it environmentally-friendly, and the approach can easily be adapted to synthesise different types of thiopeptide antiobiotics.
"There is a constant demand for new antibiotics because of the emergence of bacterial strains resistant to old antibiotics", says Dr Walczak. "This is especially true as the number of infections and deaths associated with antibiotic resistant organisms increases throughout the world. Thiopeptides represent a novel class of antibiotics capable of addressing bacterial multidrug resistance."
"We think it will be possible to use thiopeptides themselves or other molecules inspired by thiopeptides in the clinic."
This article is free to read in our open access, flagship journal Chemical Science: Siddhartha Akasapu et al., Chem. Sci., 2019, Accepted Manuscript. DOI: 10.1039/C8SC04885A. You can access all of our ChemSci Picks in this article collection.
Read more like thisChemSci Pick of the Week
Chemical Science is the flagship journal of the Royal Society of Chemistry and publishes findings of exceptional significance from across the chemical sciences. It is a global journal for the discovery and reporting of breakthroughs in basic chemical research, communicated to a worldwide audience without barriers, through open access. All article publication charges have been waived, meaning that the journal is free to read and free to publish.
Every Wednesday we are sharing one story from Chemical Science, highlighting the cutting-edge work we publish. Follow @ChemicalScience and #ChemSciPicks on Twitter to stay up to date.
If you are a journalist wishing to receive brand new research from our journals under embargo, please contact the press office using the contact box below, to be added to our distribution list.
Press office
- Tel:
- +44 (0) 20 7440 3351
- Email:
- Send us an email