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SynBio-SynChem Approaches to Diversifying the Pacidamycins through the Exploitation of an Observed Pictet-Spengler Reaction |
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| Authors: | Dr. Christopher Cartmell Dr. Antoine Abou Fayad Dr. Rosemary Lynch Dr. Sunil V. Sharma Dr. Nils Hauck Dr. Bertolt Gust Prof. Dr. Rebecca J. M. Goss |
| Affiliation: | 1. School of Chemistry and BSRC, University of St Andrews, St Andrews, Fife, KY16 9ST UK Department of Chemistry, University of Prince Edward Island Charlottetown, Prince Edward Island, C1A 4P3 Canada;2. School of Chemistry and BSRC, University of St Andrews, St Andrews, Fife, KY16 9ST UK Department of Experimental Pathology, Immunology and Microbiology Faculty of Medicine. Center of Infectious Disease Research (CIDR) WHO Collaborating Center for Reference and Research on Bacterial Pathogens, American University of Beirut, Riad El-Solh/Beirut, 1107 2020 Lebanon;3. School of Chemistry and BSRC, University of St Andrews, St Andrews, Fife, KY16 9ST UK;4. Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard-Karls-Universität, Auf der Morgenstelle 8, 72076 Tübingen, Germany |
| Abstract: | A nonenzymatic Pictet-Spengler reaction has been postulated to give rise to a subset of naturally occurring uridyl peptide antibiotics (UPAs). Here, using a combination of strain engineering and synthetic chemistry, we demonstrate that Pictet-Spengler chemistry may be employed to generate even greater diversity in the UPAs. We use an engineered strain to afford access to meta-tyrosine containing pacidamycin 4. Pictet-Spengler diversification of this compound using a small series of aryl-aldehydes was achieved with some derivatives affording remarkable diastereomeric control. |
| Keywords: | compound diversification natural products pacidamycin Pictet-Spengler semisynthesis uridyl peptide antibiotic |