Practical Synthesis of Macrobicyclic Thiolincosamines
Scalable syntheses of the northern macrobicyclic thiolincosamine fragments of two structurally complex antibiotic candidates, BT-33 and cresomycin, are presented. A key transformation in each route is the highly diastereoselective addition of a putative allenylzinc nucleophile to a common Ellman sulfinimine intermediate using a zinc-promoted Barbier-type propargylation protocol that is detailed herein. These transformations proceed with dynamic kinetic resolution and use just 1.2 equiv of each respective propargyl bromide precursor.
Authors
- Kelvin J. Y. Wu (ORCID: https://orcid.org/0000-0002-5561-6369)
- Ben I.C. Tresco
- Andrew G. Myers (ORCID: https://orcid.org/0000-0001-9602-6915)
- Dominic N. Y. See (ORCID: https://orcid.org/0009-0006-0466-9117)
- Junzhe Xiao (ORCID: https://orcid.org/0000-0003-2361-3507)
Institutions
- Harvard University (US)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2024-10-12
- DOI
- https://doi.org/10.1021/jacs.4c11270
- Citations
- 2
- Primary Topic
- Carbohydrate Chemistry and Synthesis
- Type
- article
- Field-Weighted Citation Impact
- 0.50
Funders
- National Science Foundation
- U.S. Department of Health and Human Services
- Wellcome Trust
- Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator
- Department of Health and Social Care
- Bundesministerium für Bildung und Forschung
- National Institutes of Health
- Biomedical Advanced Research and Development Authority
- National Institute of Allergy and Infectious Diseases