Natural products have been a source of inspiration for modern medicine, novel chemistries, and understanding the ecological systems with which organisms inhabit. Natural products are traditionally biosynthesized via enzymes and other chemistry catalyzing proteins. But within that framework there exists natural products that contain one or more non-enzymatic steps in their biosynthesis. In the context of this thesis, we have synthesized two natural products that contain one or more non-enzymatic steps in their biosynthesis: oxazinin A and the pyonitrins. To further elucidate these rare biosynthetic mechanisms, we have utilized 1H-15N NMR with isotopically labeled substrates to study the formation of these natural products and gain further insight into how these molecules form. This information allows us to not only see trends in terms of what kinds of natural products may form non-enzymatically but to exploit that non-enzymatic chemistry to get to natural products and natural product analogs in higher yields and faster times than traditional isolation. Furthermore, these natural products can be combined to form novel unnatural products that are not found in nature but may have ameliorated or altered bioactivity.