| Title: |
Chemoenzymatic total synthesis of the antibiotic (−)-13-deoxytetrodecamycin using the Diels-Alderase TedJ |
| Authors: |
Russell SJ; Back CR; Perry C; Cheung KA; Maschio L; Charlton SN; Lees NR; Manzo-Ruiz M; Hayes MA; van der Kamp MW; Race PR; Willis CL |
| Source: |
Chemical Science, 17 September 2025 |
| Publisher Information: |
Royal Society of Chemistry |
| Publication Year: |
2025 |
| Collection: |
Newcastle University Library ePrints Service |
| Description: |
© 2025 The Royal Society of Chemistry. The tetrodecamycins are tetracyclic natural products that exhibit potent antimicrobial activity against a multitude of drug-resistant pathogens. These compounds are structurally distinguished by the presence of a tetronate ring and trans-decalin with six contiguous asymmetric centres united by a seven-membered oxygen heterocycle. Herein we describe the first total synthesis of the antibiotic (−)-13-deoxytetrodecamycin. Our strategy is predicated on an enantioselective [4 + 2]-cycloaddition catalysed by the FAD-dependent Diels-Alderase TedJ, forming the trans-decalin with concomitant creation of two rings and four contiguous stereocenters with exquisite selectivity under mild conditions. In complementary studies, in vitro enzyme assays, X-ray crystallography and computational modelling are used to provide molecular insights into the TedJ catalysed reaction. These studies illustrate the power of adopting a chemoenzymatic approach for the enantioselective synthesis of a target compound which would be difficult to achieve using non-biological methods and provide a practical demonstration of the use of Diels-Alder biocatalysts in total synthesis. This approach has potentially widespread value in the global challenge of discovery and development of new antibiotics. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
https://eprints.ncl.ac.uk/307913; https://eprints.ncl.ac.uk/fulltext.aspx?url=307913/92B03A6A-46FE-489B-9700-9E3E393823FD.pdf&pub_id=307913 |
| Availability: |
https://eprints.ncl.ac.uk/307913 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.80325E0D |
| Database: |
BASE |