The primary objective of this research program is to continue to develop a combination of novel synthetic methods and new strategies for the synthesis of bioactive heterocycles and heterocyclic natural products. Emphasis will be placed upon producing and refining methodology having potentially broad applicability which will be of practical value to both organic and medicinal chemists involved in synthesis of cancer chemotherapeutic agents. In addition, studies will be conducted on total synthesis of a number of structurally unique and complex nitrogen-containing natural products, many of which have significant cytotoxic activity. A major goal involves utilization of our novel intramolecular allenylsilane imino ene reaction, discovered in previous years of this grant, as a pivotal step in total synthesis of the cytotoxic Lycopodium alkaloid lyconadin A. Total syntheses of the structurally unique cytotoxic marine natural products perophoramidine and the communesins will be completed using a halogen-selective tandem Heck/carbonylation strategy as a key strategic step. A total synthesis of the unusual cyclopropane-containing alkaloid lundurine A is in progress and will be completed, as will a new stereoselective total synthesis of the immunosuppressant agent FR901483.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Medicinal Chemistry Study Section (MCHA)
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Lees, Robert G
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Pennsylvania State University
Schools of Arts and Sciences
University Park
United States
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Seo, Jae Hong; Liu, Peng; Weinreb, Steven M (2010) Evolution of a strategy for total synthesis of the marine fungal alkaloid (+/-)-communesin F. J Org Chem 75:2667-80
Liu, Peng; Seo, Jae Hong; Weinreb, Steven M (2010) Total synthesis of the polycyclic fungal metabolite (+/-)-communesin F. Angew Chem Int Ed Engl 49:2000-3
Li, Puhui; Majireck, Max M; Korboukh, Ilia et al. (2008) A mild, efficient method for the oxidation of alpha-diazo-beta-hydroxyesters to alpha-diazo-beta-ketoesters. Tetrahedron Lett 49:3162-3164
Korboukh, Ilia; Kumar, Praveen; Weinreb, Steven M (2007) Construction of bridged and fused ring systems via intramolecular Michael reactions of vinylnitroso compounds. J Am Chem Soc 129:10342-3
Jeong, Jeannie H; Weinreb, Steven M (2006) Formal total synthesis of the cytotoxic marine ascidian alkaloid haouamine A. Org Lett 8:2309-12
Kropf, Jeffrey E; Meigh, Ivona C; Bebbington, Magnus W P et al. (2006) Studies on a total synthesis of the microbial immunosuppresive agent FR901483. J Org Chem 71:2046-55
Seo, Jae Hong; Artman 3rd, Gerald D; Weinreb, Steven M (2006) Synthetic studies on perophoramidine and the communesins: construction of the vicinal quaternary stereocenters. J Org Chem 71:8891-900
Weinreb, Steven M (2006) Studies on total synthesis of the cylindricine/fasicularin/lepadiformine family of tricyclic marine alkaloids. Chem Rev 106:2531-49
Majireck, Max M; Weinreb, Steven M (2006) A study of the scope and regioselectivity of the ruthenium-catalyzed [3 + 2]-cycloaddition of azides with internal alkynes. J Org Chem 71:8680-3
VanBrunt, Michael P; Ambenge, Reuben O; Weinreb, Steven M (2003) A mild, convenient, and inexpensive procedure for conversion of vinyl halides to alpha-haloketones. J Org Chem 68:3323-6

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