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The Micalizio Lab

Research

GCM10-COPA1 molecule

A central focus of modern synthetic organic chemistry is the design of new reactions and synthesis strategies that will facilitate the construction of complex molecules. We are interested in developing fundamental approaches to the assembly of stereochemically dense architecture that have the potential to facilitate investigations aimed at discovery of biologically active small molecules.


Our lab is composed of three core components as a means to realize our goals:

  • Reaction Methodology/Synthesis Strategy: This area of research is the central focus of our efforts to define enabling techniques for the facile synthesis of complex molecules. We are particularly concerned with issues regarding stereo- and regiocontrol in the development of new carbon-carbon bond-forming processes.

    The overall goal of our efforts is to define chemical methods and synthetic strategies that provide for a reduction in the number of chemical transformations required to prepare complex molecules. This goal is coupled to the search for general concepts that are applicable to the synthesis of a wide range of structurally diverse targets.

    1. Greszler, H. A. Reichard, G. C. Micalizio, “Asymmetric Synthesis of Dihydroindanes by Convergent Alkoxide-Directed Metallacycle-Mediated Bond Formation” J. Am. Chem. Soc. 2012, 134, 2766-2774.
    2. M. Z. Chen, G. C. Micalizio “Three-Component Coupling Sequence for the Regiospecific Synthesis of Substituted Pyridines” J. Am. Chem. Soc. 2012, 134, 1352-1356.
    3. D. Yang, G. C. Micalizio, “Convergent and Stereodivergent Synthesis of Complex 1-Aza-7-Oxabicyclo[2.2.1]heptanes” J. Am. Chem. Soc. 2011, 133, 9216-9219.
    4. T. K. Macklin, G. C. Micalizio, “Convergent and Stereospecific Synthesis of Skipped Polyenes and Polyunsaturated Fatty Acids” Nature Chem. 2010, 2, 638-643.
    5. D. Yang, G. G. Micalizio, “A Convergent Stereoselective Synthesis of Quinolizidines and Indolizidines: Chemoselective Coupling of 2-Hydroxymethyl Substituted Allylic Silanes with Imines” J. Am. Chem. Soc. 2009, 131, 17548-17549.
    6. M. Takahashi, M. McLaughlin, G. C. Micalizio, “Complex Allylation by the Direct Cross-Coupling of Imines with Unactivated Allylic Alcohols” Angew. Chem. Int. Ed. 2009, 48, 3648-3652.
  • Natural Product Synthesis: In concert with our efforts focusing on the development of new synthetic methods, we are actively engaged in research aimed at demonstrating the utility of these methods in the synthesis of biologically important natural products.

    For representative examples, see:

    1. M. A. Tarselli, K. M. Raehal, A. K. Brasher, C. Groer, M. D. Cameron, L. M. Bohn, G. C. Micalizio, “Synthesis of Conolidine, a Potent Non-Opioid Analgesic for Tonic and Persistent Pain” Nature Chem. 2011, 3, 449-453.
    2. V. Jeso, G. C. Micalizio, “Total Synthesis of Lehualide B by Allylic Alcohol–Alkyne Reductive Cross-Coupling” J. Am. Chem. Soc. 2010, 132, 11422-11424.
    3. T. K. Macklin, G. C. Micalizio, “Total Synthesis and Structure Elucidation of (+)-Phorbasin C” J. Am. Chem. Soc. 2009, 131, 1392-1393.
    4. H. A. Reichard, J. C. Rieger, G. C. Micalizio, “Total Synthesis of Callystatin A by Titanium-mediated Reductive Alkyne–Alkyne Cross-Coupling” Angew. Chem. Int. Ed. 2008, 47, 7837-7840.
    5. J. K. Belardi, G. C. Micalizio, “Total Synthesis of Macbecin I” Angew. Chem. Int. Ed. 2008, 47, 4005-4008.
  • Diversity-Oriented Synthesis:
    Discovery-Oriented Synthesis: Our approach to the design, discovery, and development of new reaction methods and synthesis strategies to complex molecules has the potential of providing enabling technologies suitable to drive efforts targeting the discovery of new biologically relevant small molecules. We are actively involved in such programs, and focus on developing the basic organic chemistry necessary to drive such pursuits. To date, these efforts take the form of targeting synthetic variants of natural products with potential therapeutic value, as well as an unbiased diversity-oriented approach, where common natural product motifs provide inspiration for the synthesis of large and diverse small molecule compound collections from which novel biological probes and/or therapeutics can discovered. In each case, our efforts are soundly grounded in organic synthesis while our goals target interdisciplinary and collaborative pursuits at the interface between chemistry, biology and medicine.

    For representative examples, see:

    1. C. Aquino, M. Sarkar, M. J. Chalmers, K. Mendez, T. Kodadek, G. C. Micalizio “A Biomimetic Polyketide-Inspired Approach to Small Molecule Ligand Discovery” Nature Chem. 2012, 4, 99-104.
    2. V. Jeso, L. Cherry, T. K. Macklin, S. C. Pan, P. V. LoGrasso, G. C. Micalizio “Convergent Synthesis and Discovery of a Natural Product-Inspired Paralog-Selective Hsp90 Inhibitor” Org. Lett. 2011, 13, 5108-5111.

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