Abstract

Specific Aim 1: Development of the Macrocyclic Enyne RCM Reaction a. Accumulation of new knowledge from a systematic study of previously unexplored macrocycle-forming enyne metathesis by developing new general substrate platforms. b. The study of ring size-dependency and substituent effect in the enyne metathesis reaction. c. Exploration of the parameters that control exo/endo-mode in ring-closure and the E/Z selectivity of the resultant cyclic 1,3-dienes. d. Mechanistic study to address one of the controversial issues in enyne metathesis regarding the initiation.
Specific Aim 2 : Development of a Silicon-tethered Tandem Enyne Metathesis for the Construction of Macrocyclic Carbocycles and Macrolides a. Development of silicon tether strategy for tandem enyne RCM and the efficient synthesis of silyl ethers and silaketals. b. Application of silicon-tethered tandem enyne RCM reaction to a total synthesis of (+)-cochleamycin.
Specific Aim 3 : Synthesis of Biogenetic Precursors of the Enediyne Core of C-1027 using Macrocyclic Enyne RCM Reaction a. Development of novel strategy based on enyne RCM reaction for the synthesis of enediyne natural products. b. The study of the reactivity and selectivity of the conjugated alkynyl alkylidenes. c. Efficient synthesis of a variety of putative biogenetic precursors of a potent antitumor agent C-1027. d. (Long-term goal) Collaborative research with Professor Ben Shen of School of Pharmacy at UW-Madison by integrating the tools for chemical synthesis and biosynthesis for the elucidation of biosynthetic pathway of enediyne natural product C-1027.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA106673-03
Application #
7153483
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Lees, Robert G
Project Start
2004-12-15
Project End
2007-11-30
Budget Start
2006-12-01
Budget End
2007-11-30
Support Year
3
Fiscal Year
2007
Total Cost
$218,651
Indirect Cost

  Institution

Name
University of Wisconsin Madison
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715

  Publications

Li, Jingwei; Lee, Daesung (2010) Application of a tandem metathesis to the synthesis of (+)-panepophenanthrin. Chem Asian J 5:1298-302
Yun, Sang Young; Kim, Mansuk; Lee, Daesung et al. (2009) Structure and reactivity of alkynyl ruthenium alkylidenes. J Am Chem Soc 131:24-5
Li, Jingwei; Park, Sangho; Miller, Reagan L et al. (2009) Tandem enyne metathesis-metallotropic [1,3]-shift for a concise total syntheses of (+)-asperpentyn, (-)-harveynone, and (-)-tricholomenyn A. Org Lett 11:571-4
Mukherjee, Sumit; Lee, Daesung (2009) Application of tandem ring-closing enyne metathesis: formal total synthesis of (-)-cochleamycin A. Org Lett 11:2916-9
Mukherjee, Sumit; Kontokosta, Dimitra; Patil, Aditi et al. (2009) Improved method for the synthesis of beta-carbonyl silyl-1,3-dithianes by the double conjugate addition of 1,3-dithiol to propargylic carbonyl compounds. J Org Chem 74:9206-9
Wang, Kung-Pern; Yun, Sang Young; Lee, Daesung et al. (2009) Structure and reactivity of alkyne-chelated ruthenium alkylidene complexes. J Am Chem Soc 131:15114-5
Cho, Eun Jin; Lee, Daesung (2008) Total synthesis of (3R,9R,10R)-panaxytriol via tandem metathesis and metallotropic [1,3]-shift as a key step. Org Lett 10:257-9
Cho, Eun Jin; Lee, Daesung (2007) Selectivity in the ruthenium-catalyzed alder ene reactions of di- and triynes. J Am Chem Soc 129:6692-3
Kim, Yi Jin; Grimm, Jonathan B; Lee, Daesung (2007) Absence of the Thorpe-Ingold Effect by gem-Diphenyl Groups in Ring-Closing Enyne Metathesis. Tetrahedron Lett 48:7961-7964
Park, Sangho; Lee, Daesung (2006) Gold-catalyzed intramolecular allylation of silyl alkynes induced by silane alcoholysis. J Am Chem Soc 128:10664-5

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