Microscale yeast mediated enantiospecific reduction of vanillin, and the absolute configuration of (-)-(R)-[alpha]-deuteriovanillyl alcohol: A bioorganic chemistry experiment

Abstract

An experiment is introduced to a sophomore chemistry course that demonstrates the effeciency and enantiospecificity of microbial/enzyme-mediated reactions and the use of NMR methods in determining the optical activity and absolute configuration of chiral alcohols.

Incorporating Interlab Collaborations into the Organic Chemistry Teaching Laboratories

“…In the first experiment, students explore the stereoselectivity of the yeast-mediated or sodium borohydride-mediated reduction of vanillin by running reductions using yeast with deuterium oxide or sodium borodeuteride, respectively, and then analyzing their products using polarimetry. 58 In the second experiment, students perform a multistep synthesis involving a Michael addition and elimination, a Gould−Jacobs reaction, and then a bimolecular nucleophilic substitution (S N 2) reaction to isolate and characterize the antibiotic derivative ethyl nalidixate (Scheme 1). 59 Synthetic steps 1 and 3 were modified from the original procedure to use microwave heating (vide infra).…”

“…Furthermore, an initial failed or suboptimal result could be intentionally integrated into these interlab collaborations in the future, although it would be very important for the instructor to test any procedural modifications to reveal potential safety issues. 58 and experiment 2 is Synthesis of Ethyl Nalidixate. 59 b In the nonmajors organic course, groups A and B are in different lab sections that meet at the same times every other week (e.g., one group meets every other Wednesday morning).…”

“…In the majors organic course, groups A and B are in different lab sections at different times (e.g., Monday afternoon and Tuesday morning). In some cases, these experiments were altered from those presented in the literature 58,59 to create additional challenges within teams. For example, the two-part synthesis of ethyl nalidixate 59 was modified so that the first group of students would not be able to finish their work.…”

“…When asked about the frequency and severity of process, task, and relationship conflicts, students responded very low on a Likert scale, with averages between 1 and 1.7 for collaborative experiments 1 ("Stereoselectivity of Vanillin Reduction" 58 ) and 2 ("Synthesis of Ethyl Nalidixate"; 59 Table 6 and Figure 3). The categories rated highest for both experiments include Task Conflict 1 (T1) and Task Conflict 3 (T3).…”

“…These experiments also have medicinal and/or biological applications to spark student interest (refer to the Supporting Information for example lab handouts), although any type of experiment with an even number of parts could be used. In the first experiment, students explore the stereoselectivity of the yeast-mediated or sodium borohydride-mediated reduction of vanillin by running reductions using yeast with deuterium oxide or sodium borodeuteride, respectively, and then analyzing their products using polarimetry . In the second experiment, students perform a multistep synthesis involving a Michael addition and elimination, a Gould–Jacobs reaction, and then a bimolecular nucleophilic substitution (S N 2) reaction to isolate and characterize the antibiotic derivative ethyl nalidixate (Scheme ).…”