Graduation Year
2024
Document Type
Dissertation
Degree
Ph.D.
Degree Name
Doctor of Philosophy (Ph.D.)
Degree Granting Department
Chemistry
Major Professor
Justin M. J. Lopchuk, Ph.D.
Co-Major Professor
Jams J. Leahy, Ph.D.
Committee Member
Jianfeng Cai, Ph.D.
Committee Member
Ernst Schönbrunn, Ph.D.
Keywords
Radical hydroamination, diversifiable synthesis, isotopic labeling, Fisher indole synthesis
Abstract
As an atom-economic way of carbon-nitrogen bond formation, hydroaminations are great tool for make amines, hydrazines, and other nitrogen-containing heterocycles. Specifically, radical hydroamination is a useful approach for functionalization of unactivated olefins, especially in sterically hindered environments. Diversification remains a challenge for radical hydroaminated products, since the nitrogen sources are carefully designed. In the first chapter of this dissertation, we report a highly diversifiable radical hydroamination reaction with diazirine as a nitrogen source and its potential applications in synthesis of several pharmaceutical interested compounds. Cobalt catalyzed regioselective hydroamination with diazirine shows wide function group tolerance, like phenyl thioether, ketones, esters, aldehydes, epoxy, and other function groups. More than 50 alkenes, with 16 from commercially available terpenes, shows possible synthetic application in complex molecules.
Nostodione A and scytonemin are secondary metabolite of cyanobacteria used by as UV screen pigment. After first isolation of scytonemin in 1993 and nostodione A in 1994, research was done in using scytonemin in many applications, like UV screen, radical scavenger, antiparasitic, and possible cell toxin for anti-cancer applications. The former synthetic works reported by Mårtensson and McNulty utilized center five membered ring construction as key steps with pre-set functional groups. In the second chapter of this dissertation, we reported Fisher indole synthesis based synthetic approach to synthetize both nostodione A and scytonemin from a common indole intermediate. With cyclopentane ring from starting materials, we were able to cut the steps of synthesis of nostodione A from 9 steps to 6 steps and scytonemin, from 11 steps to 7 steps.
Scholar Commons Citation
Xing, Qingyu, "Regioselective Hydroamination of Unactivated Olefins with Diazirine and Total Synthesis of Nostodione A and Scytonemin" (2024). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/10584
