Syntheses And Photo-Reactivity Of Chromene Natural Products And Photo-degradation of Steroidal Hormones

Abstract

AbstractOver the past twenty years natural products from Piper, a tropical genus of plant, have been extensively studied due to the number of biologically active natural products with unique structures. The genus Piper provides an excellent model system for exploring the relationship between natural product diversity and its impact on biotic interactions. Our group has isolated three prenylated benzoic acid derivatives, 36-38, from Piper kelleyi Tepe, a newly described species of Piper that grow in the Eastern Andes of Ecuador and Peru. These unique natural products have recently been found to significantly vary in their relative concentration and this variation was found to be a main driver of diversification of associated herbivores specifically feeding on P. kelleyi. Phytochemical variation was found to be associated with elevation, Chapters 3 of this dissertation describes our exploration of the unique photochemistry.Our biosynthetic hypothesis suggests that these three metabolites share a common pathway, where one is the precursor to the other. Recent studies unveiled that these metabolites varied significantly between individuals and that plants growing at higher elevation were chemically distinct, producing a higher concentration of all three metabolites. Given that the UV-B concentration is established to increase 15%/1,000m of elevation at the equator and the extreme phototoxicity of these metabolites to generalist herbivores, we proposed that a photochromic process involving the chromene metabolite could be driving both the phytochemical variation and the associated toxicity of the metabolites. Studies of this photochromism in the context of the natural products variation and toxicity were conducted and are the subject in chapter 2 & 3.The photochemistry of environmental contaminants, especially agricultural pharmaceuticals, has been largely understudied. While it is widely accepted that photochemical degradation of these contaminants is a primary mode of environmental clearing, reversible photochemical transformations that provide selective avenues could result in long-lived environmental contaminants and can also provide reactive pathways that produce contaminants with enhanced biological activity. Trenbolone acetate (TBA) is an anabolic steroid injected to beef cattle for muscle growth, and trace amounts of TBA leach from their manure into our aquatic systems. Risk from this contamination is eliminated as TBA rapidly photodegrades in the exposure of sunlight. Unfortunately, at night TBA regenerates causing potential risk to aquatic organisms. We have recently extended this study to understand the aquatic photochemistry of dienogest (DIE), a potent progestin analog that has structural similarities to TBA. My study demonstrates that DIE rapidly photodegrades under exposed light and reverts to dienogest when left in the dark. Additionally, we have found that continued irradiation of dienogest produces a major photoproduct that contains an aromatic A ring, like estrogen.