Syntheses and Photoreactivity of Chromene Natural Products
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Authors
Fennimore, Mary
Issue Date
2021
Type
Dissertation
Language
Keywords
Alternative Title
Abstract
Plants with high phytochemical diversity produce an abundance and varietyof secondary metabolites which increases their chance of producing potent
compounds or precursors to combat herbivory. Phototoxins are light activated
secondary metabolites that plants can produce for defense against herbivores.
Chromene compounds are naturally occurring phototoxins that serve as
precursors to toxins that aid in a plant’s defense. Piper kelleyi is a phytochemically
diverse species that contains an abundance and assortment of natural products
including compounds 1 – 3. Jeffrey Research Group isolated compounds 1 – 3
from Piper kelleyi in 2014 and hypothesized that there is a biosynthetic connection
between the three compounds. This hypothesis led to investigations into the
biosynthetic relationship between these three compounds as well as an
investigation into how the photoactivity of chromene 2 contributes to the
phytochemical diversity of Piper kelleyi. The indication of a biosynthetic connection
between 1 – 3 gave inspiration for further studies that were conducted with various
chromene natural products.
2H-Chromenes are light-activated pharmacophores that form ortho-quinone
methide intermediates upon irradiation with UV light. The short-lived, highly
reactive ortho-quinone methide intermediate can be utilized in a variety of
reactions to produce a library of natural products. The research presented
throughout this dissertation demonstrates that the reactivity of the chromene is
differentially related to its structure in all the reactions that were explored including
nucleophilic trapping, dimerization, and electrophilic aromatic substitution. The
nucleophilic trapping and subsequent dimerization reactions presented suggest
that the addition of a phenol group on the benzopyran ring changes the reactivity
of the chromene. In addition, various 2H-chromene compounds were utilized as
electrophiles in light mediated electrophilic aromatic substitution (EAS) reactions.
The total syntheses of piperaduncin A and piperaduncin B, isolated from Piper
aduncum, were achieved through light mediated EAS. This achievement
demonstrates the utility of the OQM intermediate and its ability to serve as an
intermediate in natural product synthesis. EAS reactions with various chromenes
and electron-rich aryl groups demonstrate that the reactivity of the OQM
intermediate as an electrophile is dependent on the structure of the chromene.
Herbivory of Piper kelleyi leads to oxidation products and increased
compositional diversity. Due to this conclusion, oxidation reactions were performed
to determine possible oxidation products present in Piper kelleyi. As series of
oxidation reactions utilizing prenylated benzoic acid 1 and chromene 2 produced
various oxidation products. These reactions demonstrated the labile nature of
compounds 1 and 2 and give insight into potential oxidation pathways occurring in
Piper kelleyi. The oxidation reactions presented could be relevant to the
phytochemical landscape of Piper kelleyi.