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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL025848-20
Application #
6056165
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Abraham, Kristin M
Project Start
1980-01-01
Project End
2001-08-31
Budget Start
1999-09-01
Budget End
2000-08-31
Support Year
20
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Chemistry
Type
Other Domestic Higher Education
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Hartung, John; J D Wright, Benjamin; Danishefsky, Samuel J (2014) Studies toward the total synthesis of pluraflavin A. Chemistry 20:8731-6
Pham, Hung V; Paton, Robert S; Ross, Audrey G et al. (2014) Intramolecular Diels-Alder reactions of cycloalkenones: stereoselectivity, Lewis acid acceleration, and halogen substituent effects. J Am Chem Soc 136:2397-403
Zhang, Qiang; Johnston, Eric V; Shieh, Jae-Hung et al. (2014) Synthesis of granulocyte-macrophage colony-stimulating factor as homogeneous glycoforms and early comparisons with yeast cell-derived material. Proc Natl Acad Sci U S A 111:2885-90
Townsend, Steven D; Ross, Audrey G; Liu, Kai et al. (2014) Stereospecific cis- and trans-ring fusions arising from common intermediates. Proc Natl Acad Sci U S A 111:7931-5
Peng, Feng; Grote, Robin E; Wilson, Rebecca M et al. (2013) Pattern recognition analysis in complex molecule synthesis and the preparation of iso-Diels-Alder motifs. Proc Natl Acad Sci U S A 110:10904-9
Wang, Ting; Danishefsky, Samuel J (2013) Solid-phase peptide synthesis and solid-phase fragment coupling mediated by isonitriles. Proc Natl Acad Sci U S A 110:11708-13
Wang, Ping; Dong, Suwei; Shieh, Jae-Hung et al. (2013) Erythropoietin derived by chemical synthesis. Science 342:1357-1360
Wilson, Rebecca M; Dong, Suwei; Wang, Ping et al. (2013) The winding pathway to erythropoietin along the chemistry-biology frontier: a success at last. Angew Chem Int Ed Engl 52:7646-65
Ross, Audrey G; Townsend, Steven D; Danishefsky, Samuel J (2013) Halocycloalkenones as Diels-Alder dienophiles. Applications to generating useful structural patterns. J Org Chem 78:204-10
Peng, Feng; Dai, Mingji; Angeles, Angie R et al. (2012) Permuting Diels-Alder and Robinson Annulation Stereopatterns. Chem Sci 3:3076-3080

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