Authors

Chi-Feng Lin

Type

Text

Type

Dissertation

Advisor

Ojima, Iwao | Kerber, Robert C.Goroff, Nancy S.Gupta, Ramesh C..

Date

2012-08-01

Keywords

Organic chemistry

Department

Department of Chemistry

Language

en_US

Source

This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.

Identifier

http://hdl.handle.net/11401/71322

Publisher

The Graduate School, Stony Brook University: Stony Brook, NY.

Format

application/pdf

Abstract

Among methods of asymmetric synthesis, transition-metal catalyzed asymmetric transformation has proven to be a highly efficient and enabling methodology to induce desired chirality. In our laboratory, libraries of novel biphenol-based monodentate phosphoramidite and bidentate diphosphonite ligands have been developed, which are very effective in asymmetric allylic transformations. We present here the application of Pd-catalyzed intramolecular asymmetric allylic amination to the synthesis of enantiopure key intermediates, 1-vinyltetrahydroisoquinolines in the total synthesis of Schulzeines A-C using our diphosphonite ligands. Schulzeines A-C, isolated from a marine sponge, Penares Schulzei, have been identified as a new class of marine natural products, which exhibit potent alpha-glucosidase inhibitory activity making them promising leads for drug development for cancer, diabetes, viral infections and other diseases. We also studied a highly efficient Pd-catalyzed asymmetric tandem allylic alkylation process for the synthesis of an advanced key intermediate to (-)-Huperzine A with excellent enantioseletivity using our phosphoramidite ligands. (-)-Huperzine A, isolated from the plant firmoss, Huperzia serrata, is an acetylcholinesterase (AChE) inhibitor and shows promise in the treatment of Alzheimer's disease and enhance memory. Besides, Pd-catalyzed asymmetric Heck reaction, chiral biphenol-based phosphoric acid mediated asymmetric organocatalysis and Rh-catalyzed [2+2+2+1] cycloaddition of enediynes were investigated and highlighted in the dissertation as well. | 349 pages

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