Michael J. Fuertes |
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Students in my laboratory will be trained in the art of organic synthesis, employing creative organic chemistry in the total synthesis of structurally challenging natural and unnatural products, which possess interesting pharmacological profiles and hence potential therapeutic value. Integral to this research campaign is two-fold: (1) the development and application of new synthetic methods to successfully and efficiently construct these unique molecular frameworks; and (2) the critical evaluation of these target molecules, i.e. the synthesis of analogs or mimetics, to gain a better understanding of the molecular basis of peptide and protein interactions and elucidate further how certain biological processes occur, e.g. identifying the mechanism of action leading to the death of cancer cells.
A major challenge in organic synthesis today is to devise reactions that not only can form several carbon-carbon and/or carbon-heteroatom bonds efficiently in one operation leading to the construction of polycyclic structures, but also form these bonds with proper regio- and stereocontrol. The stereoselective preparation of highly substituted oxygen and nitrogen heterocycles has attracted considerable attention in recent years given their increased recognition as common structural units in bioactive, naturally occurring compounds. Due to the heightened interest in these molecules as leads in chemotherapy and further drug development, the impetus to design new methodologies to construct such systems cannot be overemphasized. Some bioactive targets of interest include (1) ineleganolide, a cytotoxic norditerpenoid isolated from the Formosan soft coral Sinularia inelegans; (2) superstolide A, a 16-membered macrolide that is highly cytotoxic against a variety of cancer cell lines; (3) manadomanzamine A, a marine alkaloid that exhibits strong activity against Mycobacterium tuberculosis (Mtb), human immunodeficiency virus (HIV-1), and moderate activity against several AIDS opportunistic infections; (4) kirkinine, which exhibits extremely potent neurotrophic behavior, promoting neuronal survival comparable to that of nerve growth factor; (5) the antitumor antibiotic TMC-69 and analogs; and (6) the jatrophane diterpenoids, multi-drug resistant modulators which act by inhibiting the production of permeability glycoprotein in the plasma membrane.

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