Porco Lab Publication Appears in High Impact Journal
The high-impact science journal, Nature Chemistry, has published a paper by Professor John A. Porco, Jr., and his colleagues reporting on “Atropselective syntheses of (-) and (+) rugulotrosin A utilizing point-to-axial chirality transfer” (2 February 2015). Rugulotrosin A is a symmetric dimer isolated from an uncharacterised species of Penicillium. The compound displays significant antibacterial activity against a wide range of Gram positive bacteria. Investigating this important compound, the project was conceived by former Porco Group graduate student, Dr. Tian Qin (now a Postdoctoral Associate in the Baran Laboratory at Scripps Research Institute) and Professor Porco. Collaborators for the project included Professor Richard P. Johnson and his colleague Sarah L. Skrabe-Joiner at the University of New Hampshire (Durham, NH) who performed computational studies and Professor Robert J. Capon and Dr. Zeinab Khalil of the Institute of Molecular Bioscience at the University of Queensland (Australia) who carried out natural extract comparisons and biological studies.
Overall, the project team developed a concise, atropselective approach to rugulotrosin A and stereoisomers through point-to-axial chirality transfer which facilitated determination of the absolute configuration of rugulotrosin A. Computational studies modelling the geometry of intermediate diaryl Pd(II) complexes provided a rationale for the atropselectivity observed in the key Suzuki dimerization. Through HPLC analysis of fungal extracts and synthetic samples, it was determined that Penicillium nov. sp. (MST-F8741) generates rugulotrosin A in an atropselective manner. Moreover, the atropisomers and enantiomers of rugulotrosin A were found to have different activities against Gram-positive bacteria, illustrating the importance of stereochemistry on target selectivity.