The Petasis Reaction: Microscale Synthesis of a Tertiary Amine Antifungal Analog

Abstract

Students prepare a tertiary amine antifungal analog in an upper-level undergraduate organic laboratory. A microscale Petasis reaction is performed to generate a liquid compound readily characterized via IR and proton NMR spectroscopy. The biological relevance of the product is highlighted, with the tertiary amine scaffold being an important treatment option for resistant bacterial and fungal infections. The procedure allows for postlaboratory discussion of nitrogen as a stereocenter in an ammonium ion, along with principles of combinatorial chemistry and green chemistry. Deliberation of potential mechanisms for the Petasis reaction provides another valuable learning opportunity for students.

Reactivity and Synthetic Applications of Multicomponent Petasis Reactions

“…The PR has been developed as a powerful multicomponent transformation owing to several attractive features, such as a wide scope and relatively diverse variability for each of the three PR components, compatibility with various secondary transformations, and high stereoselectivity for the formation of functional amine products, together with other merits including mild and robust reaction conditions, ready availability of starting substrates, flexible scalability ranging from microscale to gram scale, and an atom-economical nature (Figure ). In addition to the versatile synthetic utility, the biologically relevant properties of many products make the PR a powerful tool in probe compound development and drug development. − The topic has been reviewed on several occasions in both book chapters − and journal articles, ,, either as a comprehensive summary, such as the chapter in 2005 by Petasis and the full compilation in 2010 by Candeias and coworkers, or a part of a broader topic, such as the nucleophilic addition of boronic acids and derivatives to imines, asymmetric MCRs, and stereocontrolled cascade reactions …”

The Chemistry Teaching Fellowship Program: Developing Curricula and Graduate Student Professionalism

“…Finding metrics to measure the effectiveness of the CTFP is challenging, due to the diverse nature of projects as well as the ever-changing landscape of undergraduate courses. Nevertheless, five projects have been published in the pedagogical literature − and have been infused in courses at other institutions, highlighting their novelty, quality, and merit. Fellows have also shared their projects through oral and poster presentations at local, national, and international conferences.…”

Microwave-Promoted Synthesis of a Carbocyclic Curcuminoid: An Organic Chemistry Laboratory Experiment

“…The synthesis of natural products and their analogues is pertinent to the typical undergraduate student in organic chemistry because many study (or have interest in) biology and appreciate the biological/medicinal properties that many such compounds exhibit. Analogues of natural products are common in pharmaceutical chemistry, and the synthesis of analogues is recognized as valuable in chemical education . The physical properties of the product are noteworthy (Figure ): the highly conjugated nature of the molecule, which exists primarily in the enol form, is responsible for its distinct orange-red color and the relatively low wavenumber absorption of the conjugated carbonyl system in the infrared spectrum.…”

“…Analogues of natural products are common in pharmaceutical chemistry, and the synthesis of analogues is recognized as valuable in chemical education. 3 The physical properties of the product are noteworthy (Figure 1): the highly conjugated nature of the molecule, which exists primarily in the enol form, is responsible for its distinct orange-red color and the relatively low wavenumber absorption of the conjugated carbonyl system in the infrared spectrum.…”