Event Information
I. Formal Synthesis of SCH 351448. II. Synthesis and Characterization of Largazole Analogues
- Abstract:
This dissertation focuses on two main projects that include the synthetic studies towards the biologically active natural products and their analogues. The first project describes synthetic studies towards SCH 351448 which is the first small molecule activator of the LDL-R promoter to control cholesterol levels. Two tandem sequences, allylic oxidation/conjugate addition reaction and cross-metathesis/conjugate addition reaction, were employed to construct 2,6-cis-tetrahydropyrans embedded in SCH 351448. Attempts were made to exploit the inherent C2-symmetric macrodioloide via direct dimerization using various single monomeric units. Since direct dimerization was not successful, efforts toward the total synthesis of SCH 351448 culminated in the formal synthesis of SCH 351448. The second project describes efforts towards the synthesis and characterization of two types of largazole analogues: disulfide analogues and linker analogues. Three disulfide analogues were synthesized to improve pharmacokinetics whereas four phenyl and one triazolyl analogues were prepared for HDAC isoform profiling based on the structure–activity relationship.
Ph.D. Dissertation Defense Examination Seminar
Departmental Seminar