B. Mikael Bergdahl
Associate Professor, Synthetic Organic, Bioorganic
office: GMCS 213G
- B.S/M.S. Chalmers University of Technology, Gothenburg, Sweden, 1987. Advisor: Prof. David Tanner
- Ph.D. Chalmers University of Technology, Gothenburg, Sweden, 1992. Advisor: Prof.'s Martin Nilsson and Thomas Olsson
- Post. doc. University of Notre Dame. Advisor: Prof. Paul Helquist
- Visiting scientist and lecturer. University of California, San Diego and Scripps Research Institute. Advisor: K.C. Nicolaou
- Assistant Professor at San Diego State University 1999-2005
- Associate Professor at San Diego State University since 2005
The main focus of my research is the syntheses and subsequent evaluation of biologically active target compounds having effects against various forms of cancer, rheumatoid arthritis and infectious diseases. Azaspirene, a member of the pseurotin family, represents a novel and unique anti-cancer agent, extraordinary in its ability to inhibit angiogenesis. Rather than destroying cancer cells via conventional chemotherapy and radiation, azaspirene turns off blood supply signals sent out by the tumor cells. My research is to develop the means to chemically make azaspirene and a library of hybrid pseurotin analogs with potential properties against cancer or arthritis. My research intertwines development of specifically new methodology in organic synthesis and new strategies toward relevant target molecules, e.g. Streptogramin type antibiotics, Epothilone analogs, and Cytotoxic Alkaloids (Micromide).
Specific research interests include the development of new chemical methodologies in asymmetric synthesis employing organometallic reagents, e.g. Zr, Cu, Zn, Si with the emphasis in catalytic reactions using chiral ligands. The streptogramin type antibiotics are a quite unique class of antibiotics that have been in use for nearly 40 years for the treatment of Staphylococcal infections. Due to medical concerns about antibiotic resistance of bacterial pathogens, there is an urgency to find and study new types of antibiotics. The total synthesis of a defined target molecule could play an important role in identifying such new candidates in medical treatments. Novel organocopper reactions have been used to solve key structures such as optically active acetate aldol products found in the pertinent target molecules.
Students working in my laboratory are exposed to a variety of scientific techniques: Advanced synthetic organic chemistry such as the invention of new chemistry, synthesis of chiral ligands and complex natural products, NMR spectroscopy to determine absolute stereochemistry of optically active compounds as well as determining reaction mechanisms and elusive reaction intermediates. Although a tremendous amount of new compounds are prepared in air-sensitive environments, we furthermore seek simple methods for making new complex target molecules, e.g. the aqueous Wittig reaction that recently was discovered by the best graduate students in my group (Chemical Engineering News 2005, July 25th page 49). In order to conduct chemical reactions under air-free conditions, my students are trained to handle compounds in inert- atmospheres using manifolds and Schlenk apparatus. The students in my group are also trained to characterize new compounds using spectroscopy (NMR, IR, MS) and flash- chromatography in order to make multi-gram quantities needed, particularly for long synthetic sequences. These are furthermore fundamental skills expected by a majority of pharmaceutical companies, particularly if the goal is to produce high yields as well high purity of products. My research group also has extensive international as well as domestic research collaboration, e.g. University of Melbourne Australia, Scripps Research Institute in La Jolla as well as many other Universities in California encompassing chemistry and biology.
Graduate students that are graduating from my group, either with a M.S. or Ph.D. degree, benefit from a comprehensive preparation provided by me as the mentor and the knowledge from a critical mass of graduate students from various areas of organic chemistry. My students are also trained to take their own initiatives in the laboratory setting, which has sometimes resulted in publications from this view of serendipity. My group also publishes regularly and we thrive to have those articles submitted to high- profile and internationally respected journals. One Ph.D. graduate student graduated from my group with 7 papers and a significant amount of conference abstracts in his pocket. The fruit labored from this hard-work and extraordinary preparation from my group provided a postdoctoral position at the Scripps Research Institute in La Jolla. Other graduate students have accepted position in the pharmaceutical industry such as Eli Lilly and Pfizer. Undergraduates from my group have accepted jobs using their synthetic organic skills, or to graduate programs at institutions such as USC, the Scripps Research Institute, and UC San Diego.
- New Route to the Ergoline Skeleton via Cyclization of 4-Unsubstituted Indoles Organic Lett. 2013, 2598-2600, with Burley, Scott D.; Lam, Vicky V.; Lakner, Frederick J.; Parker, M. A.
- Structure of a hepatitis C virus RNA domain in complex with a translation inhibitor reveals a binding mode reminiscent of riboswitches. PNAS 2012, 109, 5223-5228, with Dibrov, Sergey M.; Ding, Kejia; Brunn, Nicholas D.; Parker, Matthew A.; Wyles, David L.; Hermann, Thomas.
- An Efficient New Route to Dihydropyranobenzimidazole Inhibitors of HCV Replication Molecules 2011 16, 281-290, with Parker, Matthew A.; Satkiewicz, Emily; Hermann, Thomas.
- Wittig Reactions in Water Media Employing Stabilized Ylides with Aldehydes. Synthesis of alpha,beta-Unsaturated Esters from Mixing Aldehydes, alpha-Bromoesters, and Ph3P in Aqueous NaHCO3. J. Org. Chem. 2007, 72, 5244-5259, with El-Batta, A.; Jiang, C.; Zhao, W.; Anness, R.; Cooksy, A.L.
- The Conformation of Acetylated Virginiamycin and Virginiamycin M1 in explicit Solvents. Biochimica et Biophysica Acta: Proteins and Proteomics 2007, 1774, 610-618, with Ng, C. A.; Zhao, W.; Dang, J.; Separovic, F.; Brownlee, R. T. C.; Metzger, R. P.
- Copper(I) Iodide Dimethyl Sulfide Catalyzed 1,4-Additions of Alkenyl Groups From Mixed Alkenyl-Alkylzincate Reagents. Tetrahedron Lett. 2007, 48, 1761-1765, with El-Batta, A.
- Copper(I) Iodide Dimethyl Sulfide Catalyzed Addition of a Vinylzirconium Reagent. Preparation of 4-Phenyl-5(E)-Decen-2-One. Org. Synth. 2007, 84, 192-198, with El-Batta, A.
- The Conformation Flexibility of the Antibiotic Virginiamycin M1, Eur. J. Biophys. 2005, 34, 383-388, with Dang, J.; Metzger, R. P.; Brownlee, R. T. C.; Chai, A. N.; Separovic, F.
- Conjugate Additions of a Simple Monosilylcopper Reagent Using CuI-DMS; Stereoselectivities and the Dramatic Impact of DMS. J. Org. Chem. 2005, 70, 580-589, with Dambacher, J.
- Water is an Efficient Medium for Wittig Reactions Employing Stabilized Ylides and Aldehydes. Tetrahedron Lett. 2005, 46, 4473-4477, with Dambacher, J.; Zhao, W.; El- Batta, A.; Anness, R.; Jiang, C.
- Solvent Affects the Conformation of Virginiamycin M1 (Pristinamycin IIA, Streptogramin A). J. Org. Biomol. Chem. 2004, 2, 2919-2924, with Dang, J.; Separovic, F.; Brownlee, R.T.C.; Metzger, R.P.
- Difference in Conformation of Virginiamycin M1 in Chloroform and Bound Form in the 50S Ribosome or Streptogramin Acetyltransferase. Aust. J. Chem. 2004, 57, 415-418, with Dang, J.; Separovic, F.; Brownlee, R. T. C.; Metzger, R. P. This paper was featured on the cover of Australian Journal of Chemistry).
- Highly Diastereoselective Conjugate Additions of Various Monoorganocopper Reagents to Chiral Imides. Tetrahedron 2004, 60, 2097-2110, with Dambacher, J.; Anness, R.; Pollock, P.
- Direct Copper(I) Iodide Dimethyl Sulfide Catalyzed Conjugate Addition of Alkenyl Groups from Vinylzirconocene Reagents. Org. Lett. 2004, 6, 107-110, with El-Batta, A.; Hage, T. R.; Plotkin, S. Full text.
MS Theses and Ph.D. Dissertations
- Scott Burley, Master's Thesis 2013. Diversity - Optimized Route to the Ergoline Skeleton and the Efficient Synthesis of New HCV Inhibitors.
- Isabelle Nevchas, Master's Thesis 2010. Chemical Methodology toward the Total Syntheses of Virginiamycin M1 and Micromide Natural Products.
- Amer El-Batta, Ph.D. Thesis 2007. Part I: Copper(I) Iodide Dimethyl Sulfide Catalyzed 1,4-Addition of Alkenyl Groups From Alkenylzirconium and Alkenylzinc Reagents and Their Application Toward the Total Synthesis of Azaspirene Part II: Aqueous Wittig Chemistry Employing Stabilized Ylides and Aldehydes.
- Erketti Loizidou, Ph.D. Thesis 2006. co-advisor: K.C. Nicolaou at the Scripps Research Institute. Part I: Total Synthesis of Azaspiracid-3. Part II: Molecular Recognition Studies in Aqueous Solutions Facilitated by a Receptor Modified Polymer.
- Changchun Jiang, Master's Thesis 2006. Novel Aqueous Wittig Reaction and Chemical Studies Toward Total Synthesis of Micromide.
- Wen Zhao, Master's Thesis, 2006. Chemical Studies Toward the Total Synthesis of Streptogramin Group A Antibiotics: An Efficient Synthetic Pathway to Virginiamycin M1.
- Robert Anness, Ph.D. Thesis 2005. Chemical Studies Toward the Total Synthesis of Streptogramin Type A Antibiotics.
- Jesse Dambacher, Ph.D. Thesis 2004. Monoorgano- and Monosilylcuprate Reagents and Their Application Towards the total synthesis of Virginiamycin M1.
- Patrick Pollock, Master's Thesis 2002. Diastereoselective 1,4-Alkylation of Different Chiral a,b-Unsaturated imides using monoorganocopper Reagents and Iodotrimethylsilane.