The main theme of our research is the application of synthetic and bioorganic chemistry to problems of biochemical and medicinal relevance. All of the techniques of contemporary organic chemistry, spectroscopy, and chromatography are utilized in a highly interactive, multi-disciplinary environment supported by state-of-the-art instrumentation. Several projects involve collaborations with laboratories specializing in pharmacology, physiology, internal medicine, nephrology, and oncology at UT Southwestern and other institutions. Current projects include:
Natural Products Total Syntheses - (a) FR252921, a macrocyclic immunosuppressive with a novel mechanism of action; (b) Unabanol, a structurally unique cyclobutanol-containing polycycle; and (c) Annocatalin, a member of the acetogenin family of potent anti-cancer agents. A distinguishing characteristic of these syntheses is the development and exploitation of novel synthetic methodologies and strategies.
Eicosanoids- Oxygenated metabolites of arachidonic acid that function as local mediators or autacoids. They are involved in a wide variety of homeostatic and/or pathophysiologic processes including gene expression, ion and water transport, hormone secretion, hypertension, vasomodulation, angiogenesis, and inflammation. Our investigations encompass isolation and structure elucidation, chemical synthesis, regulation, and pharmacology. Emphasis is placed on (a) the structural diversity arising from the participation of cytochromes P450 in the arachidonic cascade; (b) secondary metabolic routes leading to novel, bioactive metabolites; and (c) non-enzymatic pathways that generate iso-eicosanoids.
Organometallics- A variety of chromium-, tin-, and boron-containing reagents are under development. These projects are often initiated in response to a synthetic challenge found within the context of a proposed total synthesis and are usually directed at the control of stereogenic centers or for the introduction of sensitive functionality that would be difficult to prepare by other methods.
Inositol-derived Cellular Regulators-These molecules function as cellular signal transduction or second messengers, inter-/intra-cellular regulators, and, possibly, as high potential phosphate donors. While they all incorporate an inositol core, their structures vary widely to encompass inositol polyphosphates (IPPs), phosphoinositides, GPI anchors, inositol pyrophosphates, and putative insulin mediators (PIMs). Our interests involve the elucidation of their structure, absolute configuration, SAR, and physiological role(s) as well as the development of unique molecular agonist/antagonist entities as biochemical tools.
RESEARCH INTERESTS
organometalics
total synthesis
synthetic methodology
natural products isolation and identification
medicinal chemistry
RECENT PUBLICATIONS
Bejot, R., Tesserand, S., Reddy, L.M., Barma, D.K., Baati, R., Falck, J.R., Mioskowski, C., "Stereoselective Transformations of Trihalomethylcarbinols Induced by Chromous Chloride" Angew. Chem. Int. Ed., 44:2008-2011, 2005
Kermonant-Duchemin, E., Sennlaub, F., Sirinyan, M., Brault, S., Andelfinger, G., Kooli, A., Germain, S., Ong, Hl, d’Orleans-Juste, P., Gobeil, F., Zhu, T., Boisvert, C., Hardy, P., Jain, K., Falck, J.R., Balazy, M., Chemtob, S., "Trans-Arachidonic Acids Generated During Nitrative Stress Induce a Thrombospondin-1-Dependent Microvascular Degeneration" Nat. Med., 11:1239-1245, 2005
Falck, J.R., Patel, P.K., Bandyopadhyay, A., "Stereospecific Cross-Coupling of ?-(Thiocarbamoyl)organostannanes with Alkenyl, Aryl, and Heteroaryl Iodides" J. Am. Chem. Soc., 129:790-793, 2007
Falck, J.R., He, A., Fukui, Hl, Tsutsui, H., Radha, A., "Synthesis and Sterochemical Assignment of FR25292, a Promising Immunisuppressant" Angew. Chem. Int. Ed., 46:4527-4529, 2007
SIGNIFICANT PUBLICATIONS
Baati, R., Barma, D.K., Falck, J.R., Mioskowski, C., "Chromium Vinylidene Carbenoids: Generation, Characterization, and Reactivity. First Evidence of an Internal Proton Return Phenomenon with Vinylidene Carbenoids" J. Am. Chem. Soc., 123:9196-9197, 2001
Barma, D.K., Kundu, A., Zhang, H., Mioskowski, C., Falck, J.R., "(Z)-?-Haloacrylates: An Exceptionally Steroselective Preparationv ia Cr(II)-Mediated Olefination of Aldehydes with Trihaloacetates" J. Am. Chem. Soc., 125:3218-3219, 2003
Barma, D.K., Bandyopadhyay, A., Capdevilla, J.H., Falck, J.R., "Dimethylthiocarbamate (DMTC): An Alcohol Protecting Group" Org. Lett., 5:4755-4757, 2003
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