The PI's hopes for this project are twofold. First, as a chemistry laboratory, his group proposes to develop new capabilities in synthesis, both at the strategic and methodological levels. Enhancement of strength in organic synthesis finds ready application in assembling molecules of complexity for biological scrutiny. In the HL2588 Program the focus is on a group of targets which are, per se, of interest from the standpoint of promising pre-clinical activity or novel mechanism of biological action. Thus, the targets are selected with a view to providing differing syntheses, while at the same time raising the possibility of new drug leads in the course of synthesizing substrates for probing issues of structure and mechanism. Approximately a third of the effort will be directed toward carbohydrate synthesis. Considerable attention is to directed to the synthesis of the other part of his program focuses on diverse chemical issues as part of explorations directed to the total synthesis of a collection of interesting and challenging natural product goal structures. Among these individual natural product derived projects are the phospholipase inhibitor hispidospermidin (program E); gelsemine (program F), CP 225, 917, which is a farnesyl transferase inhibitor (program g), wortmannin, which is a cell cycle modulator (program H). He also seeks to pursue the total synthesis of himastatin, also a cell cycle modulator (program I), spirotryprostatin, an agent which intervenes in the cell cycle progression at the G2/M phase (program J), tricycloillicinone, a natural product which increases acetylcholinesterase activity (program K) and disydiolide, a protein phosphatase inhibitor (program L). The proposal was discussed according to these program classifications.
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