Abstract

Efficient total synthesis of the antitumor agents actinobolin and bactobolin are proposed which both utilize the key bicyclic intermediate lactone. A route to the Lactone has been outlined which involves a stereoselective intramolecular ene-reaction of an electron deficient imine. An alternate strategy to prepare the Lactone has been described which uses an intramolecular nitrone or nitronate [3+2]-cycloaddition to afford the proper ring system and stereochemistry. Steps for the elaboration of the Lactone to actinobolin and bactobolin have been detailed. Syntheses of several C-3 analogs of actinobolin and bactobolin have also been proposed. Analogs and synthetic intermediates will be submitted to NCI for antitumor testing.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA034303-03
Application #
3172020
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1983-06-01
Project End
1986-05-31
Budget Start
1985-06-01
Budget End
1986-05-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Pennsylvania State University
Department
Type
Schools of Arts and Sciences
DUNS #
City
University Park
State
PA
Country
United States
Zip Code
16802

  Publications

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

Showing the most recent 10 out of 15 publications