Introducing Freshmen Students to the Practice of Solid-Phase Synthesis

Abstract

Background and Rationale for the Experiment Solid-phase chemistry has revolutionized the synthesis of organic compounds, peptides, oligonucleotides, carbohydrates, drugs, and combinatorial libraries (1‐5). Although many types of compounds incorporating a variety of building blocks can be created, all solid-phase syntheses share a common approach. In a typical synthesis, starting material is anchored to a polymeric support and transformed into product by the action of solution-phase reagents. The product is then liberated into solution. The reverse approach has been used to convert solution-phase reactants into products by means of supportimmobilized reagents and catalysts (6 ). Solid-phase organic synthesis is effective because reagents can be used in excess to drive reactions and immobilized products can be purified by repeated washings (7). In addition, syntheses can be automated. By combining these attractive features, multistep syntheses that would be considered unfeasible under homogeneous solutionphase conditions have been realized. The merit and popularity of solid-phase protocols are illustrated by the example of Bruce Merrifield, who received a Nobel Prize for his seminal contribution, and further, by explosive developments in combinatorial chemistry and drug discovery (5, 8‐11). Our goal was to introduce students in the early stages of academic development to the principles and practice of synthesis. Freshmen students attending a “pick-a-project” course were ideal subjects for the study. Several enrollees had expressed a curiosity in the topic of synthetic chemistry, but clearly lacked the practical experience required to carry out a multistep solution synthesis. As solid-phase methods have proven advantageous, popular, relevant, and technically facile, a project focused on solid-phase synthesis showed promise as an instructional vehicle. Peptide synthesis in particular was chosen because its chemistry has been developed to the point where success is virtually guaranteed if protocols are followed faithfully (2, 12‐14). The novelty of presenting peptide chemistry to freshmen students in a tangible, hands-on fashion rather than by using a textbook approach was also a deciding factor (15). Structure, Content, and Pedagogy Students were asked to write a project proposal, present goals, rationale, and methods to a committee, implement the proposal, document results, and conclude the project in report and oral PowerPoint format before peers and faculty. In addition to instructor guidance and support, the students had intranet access to guidelines on preparing proposals, reports, and oral presentations and to mandatory readings on the subjects of synthesis and analysis (2, 12‐18). Basic chromatography, spectrometry, spectroscopy, kinetics, and enzyme function were discussed, and detailed protocols were supplied to facilitate in-lab instruction. Project objectives were realized by adopting a guided, step-by-step, hands-on approach. The students worked and studied collaboratively in order to promote interactive learning. They were introduced to key concepts with the aid of laboratory demonstrations and visual tools and were encouraged to consolidate these concepts as they implemented the project. The completed project was archived on the intranet for the benefit of future enrollees. Synthesis, Analysis, and Application