Semester

Spring

Date of Graduation

2021

Document Type

Dissertation

Degree Type

PhD

College

Eberly College of Arts and Sciences

Department

Chemistry

Committee Chair

Gregory Dudley

Committee Member

Brian Popp

Committee Member

Aaron Robart

Committee Member

Bjorn Soderberg

Committee Member

Kung Wang

Abstract

Innovations in synthetic organic chemistry such as methodology improvements, new chemical transformations and technology development significantly impact medicinal chemistry and continue to drive the drug discovery process. Here, new cyclization strategies to the pharmaceutically underexplored 3,3-dimethylcyclopentane-fused aromatic rings are described. One approach highlighted oxidative cycloisomerization, intermolecular [2+2+2] cyclotrimerization and 5-exo-dig cyclization providing indanoylindole cannabinoids that possess high affinity for human CB2 receptors at nanomolar concentration and good selectivity index. Another featured a [4+2]-type benzannulation reaction which enabled the 5-step synthesis of illudalic acid — compared to the current available sequences (≥16 steps) — and its equipotent and LAR-selective analogs. Outside reaction innovation, new findings on possible opportunities for selective microwave heating in organic synthesis are also reported. The coordinated, cooperative use of MW heating and conventional heating in heterogeneous mixtures comprising ionic, highly microwave-absorbing organic reagents and nearly microwave-transparent arene solvents resulted in accelerated reactions compared to MW and conventional heating alone.

Embargo Reason

Publication Pending

Available for download on Thursday, April 07, 2022

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