I. Total synthesis of sesquiterpene-tropolones II. Dearomative hydroamination and application to the synthesis of aminoglycosides

Ungarean, Chad Nicholas

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https://hdl.handle.net/2142/109613 Copy

Description

Title

I. Total synthesis of sesquiterpene-tropolones II. Dearomative hydroamination and application to the synthesis of aminoglycosides

Author(s)

Ungarean, Chad Nicholas

Issue Date

2020-12-03

Director of Research (if dissertation) or Advisor (if thesis)

Sarlah, David

Doctoral Committee Chair(s)

Sarlah, David

Committee Member(s)

• Denmark, Scott E
• White, M. Christina
• Silverman, Scott K

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Total synthesis
• sequiterpenes
• hydroamination
• aminoglycosides

Abstract

The first chapter discusses the development of a platform for the synthesis of a variety of bioactive sesquiterpene-tropolones. The synthetic strategy relies on the union of key fragments via an inverse electron demand hetero-Diels–Alder (HDA) reaction between either humulene or humulene derivatives and a tropolone ortho-quinone methide (o-QM). Tropolone construction utilizes [2+2] cycloaddition of a linear precursor followed by either de Mayo type or photochemical fragmentation approaches to arrive at the requisite o-QM precursor. The 10-hydroxy-–humulene component relies on a semi-synthetic route starting from caryophyllene oxide and utilizing a key HAT ring expansion to arrive at the 11-membered macrocycle. The culmination of these synthetic efforts has elucidated a reasonable biosynthesis of the pycnidione series along with the structural reassignment of several members of the class. Additionally, the synthesis of unnatural epi,epi- and epi,ent-pycnidione has been enabled. Current focus is on the construction of a library of analogs as well as the biological evaluation of these compounds. The second chapter details the development of a dearomative hydroamination methodology of simple arenes. This novel reaction was extended to several mono- and polynuclear arenes and heteroarenes. Utilizing benzene as a starting material, a divergent synthetic strategy was executed to arrive as the 2-deoxystreptamine (2-DOS) and 2-deoxyfortamine (2-DOF) aminoglycoside cores; key synthetic steps in the 2-DOS and 2-DOF cores include a 5-exo-tet cyclization and bromonium induced rearrangement. Furthermore, from these scaffolds, the synthesis of ribostamycin and istamycin have been pursued and are in the final stages of construction. Current efforts involve the global deprotection of the penultimate intermediate for ribostamycin as well as glycosylation and global deprotection for istamycin. Additionally, the synthesis of unnatural analogs is underway.

Graduation Semester

2020-12

Type of Resource

Thesis

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http://hdl.handle.net/2142/109613

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Copyright 2020 Chad Ungarean

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