NATURAL PRODUCT INSPIRED METHODOLOGIES: ADVANCES IN DIASTEREOSELECTIVE N-SULFINYL IMINE AND TRIFLUOROPYRUVIC ACID REACTIONS

My research work focused on the development of methodologies to enable efficient synthesis of natural products. In the Andrade lab I developed N-sulfinyl metallodienamine (NSMD) and metalloenamine (NSME) methodologies for the asymmetric synthesis of natural products. In 2017, our first report of a novel diastereoselective hydroxylation protocol for metallodienamine (with 4:1 dr) in concise 14-step synthesis of (−)-albocycline warranted further exploration of the method. By screening different metal bases, I was able to observe a unique diastereoselective switch. DFT computational modeling assisted with experimental analysis suggested a favoritism of metallodienamine geometry by choice of metal bases as the origin of the diastereoselective switch. The method worked well with a diverse set of N-sulfinyl aldimines and ketimines with 50-99% yield and 3:1 to 98:2 diastereoselectivity. A one-pot protocol was developed to access 1,2 amino alcohols with high diastereoselectivity. With a good understanding of the diastereoselective reaction with NSMD and NSMEs, I joined with Dr. Po-Cheng Yu to develop a highly diastereoselective domino Michael/Michael/Mannich reaction for the concise total synthesis of (+)- epiibogamine. The domino reaction enabled us to set all the stereocenters in the natural product in a single step with high diastereoselectivity enabling access to the natural product in a concise 7 steps. I also worked briefly on developing diastereoselective oxidative coupling with N-sulfinyl imine for the synthesis of (+)-chimonanthine. At the beginning of my fourth year I Joined the Kim lab, where I developed photoredox catalyzed process to synthesize y-lactones. These motifs are found in various natural products and require multistep to access. I developed a method that enables quick access to these motifs in one step.

Grantor dc:publisher

Temple University. Libraries

Year dc:date.issued

2023

Author dc:creator

• Karmakar, Anupam

Advisor dc:contributor.advisor

• Kim, Daniel K.

Committee members dc:contributor.committeemember

• Wengryniuk, Sarah E.
• Wang, Rongsheng
• Beaudry, Christopher M.

• Organic chemistry

Statement dc:rights

• IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available.

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/20.500.12613/9512

OAI identifier oai:identifier

oai:scholarshare.temple.edu:20.500.12613/9512