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Dissertation Information for Gang Shen

NAME:
- Gang Shen

DEGREE:
- Ph.D.

DISCIPLINE:
- Chemistry

SCHOOL:
- Emory University (USA) (2003)

ADVISORS:
- Debra L. Mohler

COMMITTEE MEMBERS:
- Frank E. McDonald
- Justin P. Gallivan

MPACT Status: Fully Complete

Title: I. The syntheses of the potential ligands of PPAR/RXR. II. The investigation of [2+2+3] methodology

Abstract: The optimized reaction conditions for the preparation of dipeptide and 2,4-thiazolidinedione-5-acetic acid conjugates as potential PPAR ligands were accomplished under both solution and solid phase reaction conditions. In solution, N -2-trimethylsilylethyl-2,4-thiazolidinedione-5-acetic acid was prepared and gave a good yield in the key carbodiimide/HOBt coupling reaction. In the solid phase synthesis, the use of more than two equivalents of DCC improved the yield in the coupling reaction of the resin linked dipeptide and 2,4-thiazolidinedione-5-acetic acid. This solid phase methodology was used to produce nine of the target compounds were synthesized in good to excellent overall yields. Six oligo(ethylene glycol) tethered BRL49653 and LG-100324 conjugates were synthesized as potential ligands for the PPARã/RXR heterodimer. The synthesis was accomplished via two routes. For the first more convergent synthetic route, 5-(4-(2-( N -6 \' -(2 \' -hydroxy-pyridinyl)methylamino)ethoxy)-benzyl)-2,4-thiazolidinedione was prepared as the key intermediate, which afforded the target compounds after a nucleophilic substitution and a novel hydrolysis induced by sodium hydride. The overall yields range from 0.5% to 1.6%. With the second synthetic route, the best overall yield reached 4.5%. Additionally, the control compounds, functionalized BRL49653, were synthesized in this route. A novel [2+2+3] methodology was investigated with various transition metal complexes. The substrates examined include substituted cyclopropenone, cyclopropenone acetal, and substituted cyclopropene, but none gave the proposed cycloaddition product. In the presence of several ruthenium, rhodium, and cobalt complexes, the mono-substituted cyclopropenone and cyclopropenone acetal compounds quickly undergo a ring-opening reaction to provide acrylic acid derivatives. On the other hand, disubstituted cyclopropenones are stable to the catalysts under the tested conditions.

MPACT Scores for Gang Shen

A = 0
C = 0
A+C = 0
T = 0
G = 0
W = 0
TD = 0
TA = 0
calculated 2008-03-22 23:02:57

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