Abstract

The long range objective of this research program is to develop and apply intramolecular Diels-Alder reactions in the synthesis of biologically active natural products. Although the IDA reaction promises to become a widely used synthetic transformation, complete control of stereochemistry is not yet a reality. Problems still exist with respect to control of ring fusion geometry, and asymmetric induction from preexisting stereocenters is not always satisfactory. These problems will be addressed in the next four-year grant period within the context of developing stereo-controlled syntheses of three natural products: chlorothricolide, the aglycone of the antibiotic chlorothricin; kijanolide, the aglycone of an antibiotic active against an unusual range of microorganisms including Propionibacterium and Plasmodium species; and nargenicin A1, an antibiotic with significant activity against Staphylococcus strains.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM026782-07
Application #
3274220
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1979-07-01
Project End
1989-08-31
Budget Start
1985-09-19
Budget End
1986-08-31
Support Year
7
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Massachusetts Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code

  Publications

Doherty, Joanne R; Yang, Chunying; Scott, Kristen E N et al. (2014) Blocking lactate export by inhibiting the Myc target MCT1 Disables glycolysis and glutathione synthesis. Cancer Res 74:908-20
Dossey, Aaron T; Whitaker, John M; Dancel, Maria Cristina A et al. (2012) Defensive spiroketals from Asceles glaber (Phasmatodea): absolute configuration and effects on ants and mosquitoes. J Chem Ecol 38:1105-15
Chen, Ming; Roush, William R (2011) Enantioconvergent hydroboration of a racemic allene: enantioselective synthesis of (E)-ýý-stannyl-anti-homoallylic alcohols via aldehyde crotylboration. J Am Chem Soc 133:5744-7
Halvorsen, Geoff T; Roush, William R (2011) Stereoselective Synthesis of the Decahydrofluorene Core of the Hirsutellones. Tetrahedron Lett 52:2072-2075
Sun, Huikai; Abbott, Jason R; Roush, William R (2011) Stereoselective synthesis of a model C(18)-C(35) spiroketal fragment of integramycin. Org Lett 13:2734-7
Chen, Ming; Ess, Daniel H; Roush, William R (2010) Enantioselective synthesis of (E)-delta-stannyl homoallylic alcohols via aldehyde allylboration using alpha-stannylallylboranes generated by allene hydroboration followed by a highly diastereoselective 1,3-boratropic shift. J Am Chem Soc 132:7881-3
Chen, Ming; Roush, William R (2010) Highly (E)-selective BF(3).Et(2)O-promoted allylboration of chiral nonracemic alpha-substituted allylboronates and analysis of the origin of stereocontrol. Org Lett 12:2706-9
Chen, Ming; Handa, Masaki; Roush, William R (2009) Enantioselective synthesis of 2-methyl-1,2-syn- and 2-methyl-1,2-anti-3-butenediols via allene hydroboration-aldehyde allylboration reaction sequences. J Am Chem Soc 131:14602-3
Ess, Daniel H; Kister, Jeremy; Chen, Ming et al. (2009) Quantum-mechanical study of 10-R-9-borabicyclo[3.3.2]decane alkene hydroboration. J Org Chem 74:8626-37
Ess, Daniel H; Kister, Jeremy; Chen, Ming et al. (2009) Origin of thermodynamic versus kinetic control of allene hydroboration with 9-borabicyclo[3.3.1]nonane and 10(R)-trimethylsilyl-9-borabicyclo[3.3.2]decane. Org Lett 11:5538-41

Showing the most recent 10 out of 28 publications