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
Rasko, D.A., Moriera, C.G., Li, D.R., Readings, N.C., Ritchie, J.M., Waldor, M.K., William, N., Taussig, R., Wei, S., Roth, M., Hughes, D.T., Huntley, J.F., Fina, M.W., Falck, J.R., and V. Sperandio, "Targeting QseC Signaling and Virulence for Antibiotic Development" Science, 321:1078-1080, 2008
He, A., and J.R. Falck, "Synthesis of Enantioenriched α-(Hydroxyalkl)-tri-n-butylstannanes" Angew. Chem. Int. Ed., 47:6586-6589, 2008
Lu, B., and J.R. Falck, "Efficient Iridium-Catalyzed C-H Functionalization/Silylation of Heteroarenes" Angew. Chem. Int. Ed., 47:7508-7510, 2008
Baati, R., Mioskowski, C., Kashinath, D., Kodepelly, S., Lu, B., and J.R. Falck., "Steroselective Synthesis of Methyl (Z)-α-Methoxyacrylates via Two-Carbon Homologation of Aldehydes" Tetrahedron Lett., 50:402-405, 2009
SIGNIFICANT PUBLICATIONS
Tunctan, B., Korkmaz, B., Butaralioglu, C.K., Firat, S.S., Anjaiah, S., Falck, J.R., Roman, R.J., and K.U. Malik, "A 20-Hydroxyeicosatetraenoic Acid Agonist, N-[20-Hydroxyeicosa-5(Z),14-(Z)-Dienoyl]Glycine, Opposes the Fall in Blood Pressure and Vascular Reactivity in Endotoxin-Treated Rats" Shock, 30:329-335, 2008
Falck, J.R., He, A., Fukui, H., Tsutsui, H., and A. Radha, "Synthesis and Sterochemical Assignment of FR252921, a Promising Immunosuppressant" Angew. Chem. Int. Ed., 46:4527-4529, 2007
Li, D-R., Murugan, A., and J.R. Falck, "Enantioselective, Organocatalytic Oxy-Michael Addition to γ/δ-Hydroxy-α,β-enones: Boronate-Amine Complexes as Chiral Hydroxide Synthons" J. Am. Chem. Soc., 130:46-48, 2008
Illies, C., Gromada, J., Fiume, R., Leibiger, B., Yu, J., Juhl, K., Yang, S-N., Barma, D., Falck, J.R., Saiardi, A., Barker, C.J., and P-O Berggren, "Requirement of Inositol Pyrophosphates for Full Exocytotic Capacity in Panacreatic β Cells" Science, 318:1299-1302, 2007
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