The basis of this proposal seeks the to develop new reaction methods in synthetic organic chemistry, their application to biologically active complex natural products and investigations of fundamental importance in synthetic and medicinal chemistry. This includes efforts to develop new chemistry for the [4 + 2]-annulation of enantioenriched organosilanes. An extensive investigation seeking to evaluate functionalized organosilane reagents for the stereoselective construction of dihydropyrans and tetrahydropyridine ring systems with the eventual goal in their application in synthesis. The enantioselective synthesis of the cytotoxic agent callipeltoside A and the transcription activator of low density lipoprotein receptor will pursued with emphasis on the dihydropyran annulation chemistry. ? ? Novel annulation methodology for the stereoselective synthesis of nitrogen bearing heterocycles will be directed at the synthesis of alkaloid 205B. ? ? A convergent, enantioselective synthesis of the potent cytotoxic / antifungal agent, leucascandrolide A will be achieved and will suitable for the preparation of side chain analogs with widely diversified substitution patterns. A small focused library of heterocyclic sidechain analogs will be assembled and evaluated for their effectiveness in inhibiting Candida albicans. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM055740-04A2
Application #
6824161
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Schwab, John M
Project Start
1998-05-01
Project End
2008-06-30
Budget Start
2004-07-15
Budget End
2005-06-30
Support Year
4
Fiscal Year
2004
Total Cost
$348,818
Indirect Cost
Name
Boston University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
049435266
City
Boston
State
MA
Country
United States
Zip Code
02215
Zhu, Kaicheng; Panek, James S (2011) Total synthesis of (+)-SCH 351448. Org Lett 13:4652-5
Wu, Jie; Chen, Yu; Panek, James S (2010) Vinylogous aldol products from chiral crotylsilanes obtained by enantioselective Rh(II) and Cu(I) carbenoid Si-H insertion. Org Lett 12:2112-5
Brawn, Ryan A; Panek, James S (2009) Synthesis of enantioenriched homopropargylic sulfonamides by a three component reaction of aldehydes, sulfonamides, and chiral allenylsilanes. Org Lett 11:4362-5
Zhang, Yun; Panek, James S (2007) Total synthesis of herboxidiene/GEX 1A. Org Lett 9:3141-3
Sarkar, Paramita; Reichman, Charles; Saleh, Tamjeed et al. (2007) Proline cis-trans isomerization controls autoinhibition of a signaling protein. Mol Cell 25:413-26
Youngsaye, Willmen; Lowe, Jason T; Pohlki, Frauke et al. (2007) Total synthesis and stereochemical reassignment of (+)-neopeltolide. Angew Chem Int Ed Engl 46:9211-4
Su, Qibin; Dakin, Les A; Panek, James S (2007) [4 + 2]-annulations of chiral organosilanes: Application to the total synthesis of leucascandrolide A. J Org Chem 72:2-24
Chen, Yu; Porco Jr, John A; Panek, James S (2007) Stereochemical and skeletal diversity employing pipecolate ester scaffolds. Org Lett 9:1529-32
Arefolov, Alexander; Panek, James S (2005) Crotylsilane reagents in the synthesis of complex polyketide natural products: total synthesis of (+)-discodermolide. J Am Chem Soc 127:5596-603
Su, Qibin; Panek, James S (2005) Total synthesis of (+)-leucascandrolide A. Angew Chem Int Ed Engl 44:1223-5

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