More Like this

1. Total Synthesis of UCS1025A via Tandem Carbonylative Stille Cross Coupling and Diels‐Alder Reaction ^†

   https://doi.org/10.1002/cjoc.202300331  

   Cui, Chengsen; Dai, Mingji (August 2023, Chinese Journal of Chemistry)

   Comprehensive Summary We report an efficient and convergent strategy for the total synthesis of UCS1025A and its diastereomer tetra‐epi‐UCS1025A. UCS1025A is a representative member of the naturally occurring pyrrolizidinone polyketides, from which members with potent antibacterial, antifungal, and anticancer activities have been identified. Our approach features a tandem carbonylative Stille cross coupling and Diels‐Alder reaction to forge a key C—C bond and build thetrans‐decalin system. This tandem process utilizes carbon monoxide as a one‐carbon linchpin to stitch a vinyl triflate and a vinylstannane together and form the desired enone moiety for the subsequent intramolecular Diels‐Alder cyclization. Our synthesis also provides a versatile approach for the synthesis of other related pyrrolizidinone‐containing polyketides. 

   more » « less
2. Coordination Chemistry of an Emerging Group of Diazeniumdiolate Siderophores: Crystal Structures of M(III)-Gramibactin (M= Fe and Ga)

   https://doi.org/10.1021/jacs.5c13791  

   Thomsen, Emil; Wu, Guang; Butler, Alison (September 2025, Journal of the American Chemical Society)

   To overcome iron starvation, microorganisms often produce siderophores—chelators with high affinity and selectivity for Fe(III). The recent discovery of the siderophore gramibactin garnered significant interest, as it added the C-diazeniumdiolate as a new Fe(III)-binding group in siderophores. Gramibactin is a mixed ligand siderophore, comprised of two graminine residues harboring the diazeniumdiolate donors and a β-hydroxy-aspartate donor. Diazeniumdiolate siderophores have so far evaded crystallographic characterization and few structures of synthetic diazeniumdiolate complexes are reported. To address the gap in structural information, the complexes K[M(III)-gramibactin] (M= Fe and Ga) were prepared, crystallized and their structures solved by X-ray diffraction (XRD). The four Fe-O bond lengths in the two diazeniumdiolates are quite similar, ranging from 1.978 Å to 2.059 Å, indicating an equal contribution in bonding. In contrast, the differing Fe-O bond lengths in β-hydroxy-aspartate reflect the relative donor strengths of the carboxylate (1.997 Å) and alkoxide (1.902 Å) groups. Gramibactin coordinates Fe(III) in a Δ-configured distorted octahedral geometry. The diamagnetic nature of Ga(III) is often leveraged in NMR studies to infer the solution structure of the corresponding Fe(III)-siderophores, which are assumed to be identical. The structural similarity of Ga(III)- and Fe(III)-gramibactin is striking and represents the first crystallographic verification of the assumed isostructural relationship between a Ga(III)- and an Fe(III)-siderophore. By providing concrete evidence, this study promotes Ga(III) as a reliable proxy for Fe(III) in siderophore complexes, with implications for solution structure determination of siderophores and design of Ga(III)-siderophore-based theranostics. 

   more » « less
3. Photoinduced Nitric Oxide Exchange in the Diazeniumdiolate Siderophore, Pandorachelin

   https://doi.org/10.1021/acschembio.5c00484  

   Susman, Melanie; Makris, Christina; Butler, Alison (September 2025, ACS Chemical Biology)

   C-diazeniumdiolate siderophores are a small class of photoactive bacterial Fe(III) chelators. Driven by genome mining, we discovered a new C-type diazeniumdiolate siderophore, pandorachelin, produced by the rhizospheric bacterium, Pandoraea norimbergensis DSM 11628. The biosynthetic gene cluster encoding the production of pandorachelin is conserved across several Pandoraea species. Pandoraea spp. are environmentally widespread and are increasingly prevalent clinical pathogens, spurring new interest in their metabolites. UV irradiation photolytically cleaves the N–N bonds within the diazeniumdiolate-containing graminine constituents of pandorachelin. With EPR spin trapping, we directly detect nitric oxide released from the two C-diazeniumdiolate ligands of pandorachelin upon UV irradiation. Additionally, we show that nitric oxide can react with the intermediates during the photoreaction to re-construct the diazeniumdiolate groups via exchange of the distal NO, and thereby recover Fe(III)-binding capacity. The photochemistry of this class of siderophores points to a broader biological role, both in their propensity to release the biological signaling molecule, nitric oxide, and in their ability to undergo photoinduced NO exchange. 

   more » « less
4. Mining elements of siderophore chirality encoded in microbial genomes

   https://doi.org/10.1002/1873-3468.14539  

   Butler, Alison; Jelowicki, Aneta M.; Ogasawara, Haley A.; Reitz, Zachary L.; Stow, Parker R.; Thomsen, Emil (January 2023, FEBS Letters)

   The vast majority of bacteria require iron to grow. A significant iron acquisition strategy is the production of siderophores, which are secondary microbial metabolites synthesized to sequester iron(III). Siderophore structures encompass a variety of forms, of which highly modified peptidic siderophores are of interest herein. State‐of‐the‐art genome mining tools, such as antiSMASH (antibiotics & Secondary Metabolite Analysis SHell), hold the potential to predict and discover new peptidic siderophores, including a combinatoric suite of triscatechol siderophores framed on a triserine‐ester backbone of the general class, (DHB‐ l / d CAA‐ l Ser) 3 (CAA, cationic amino acid). Siderophores with l / d Arg, l / d Lys and l Orn, but not d Orn, were predicted in bacterial genomes. Fortuitously the d Orn siderophore was identified, yet its lack of prediction highlights the limitation of current genome mining tools. The full combinatoric suite of these siderophores, which form chiral iron(III) complexes, reveals stereospecific coordination chemistry encoded in microbial genomes. The chirality embedded in this suite of Fe(III)‐siderophores raises the question of whether the relevant siderophore‐mediated iron acquisition pathways are stereospecific and selective for ferric siderophore complexes of a defined configuration. 

   more » « less
5. Siderophore production and utilization by marine bacteria in the North Pacific Ocean

   https://doi.org/10.1002/lno.12373  

   Park, Jiwoon; Durham, Bryndan P; Key, Rebecca S; Groussman, Ryan D; Bartolek, Zinka; Pinedo‐Gonzalez, Paulina; Hawco, Nicholas J; John, Seth G; Carlson, Michael_C G; Lindell, Debbie; et al (July 2023, Limnology and Oceanography)

   Abstract Siderophores are strong iron‐binding molecules produced and utilized by microbes to acquire the limiting nutrient iron (Fe) from their surroundings. Despite their importance as a component of the iron‐binding ligand pool in seawater, data on the distribution of siderophores and the microbes that use them are limited. Here, we measured the concentrations and types of dissolved siderophores during two cruises in April 2016 and June 2017 that transited from the iron‐replete, low‐macronutrient North Pacific Subtropical Gyre through the North Pacific Transition Zone (NPTZ) to the iron‐deplete, high‐macronutrient North Pacific Subarctic Frontal Zone (SAFZ). Surface siderophore concentrations in 2017 were higher in the NPTZ (4.0–13.9 pM) than the SAFZ (1.2–5.1 pM), which may be partly attributed to stimulated siderophore production by environmental factors such as dust‐derived iron concentrations (up to 0.51 nM). Multiple types of siderophores were identified on both cruises, including ferrioxamines, amphibactins, and iron‐free forms of photoreactive siderophores, which suggest active production and use of diverse siderophores across latitude and depth. Siderophore biosynthesis and uptake genes and transcripts were widespread across latitude, and higher abundances of these genes and transcripts at higher latitudes may reflect active siderophore‐mediated iron uptake by the local bacterial community across the North Pacific. The variability in the taxonomic composition of bacterial communities that transcribe putative ferrioxamine, amphibactin, and salmochelin transporter genes at different latitudes further suggests that the microbial groups involved in active siderophore production and usage change depending on local conditions. 

   more » « less