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The Silyl Enol Ether Prins Cyclization: Application to the Total Synthesis of Cyanolide A, Synthesis of Quinolizidine and Indolizidine Heterocycles Using Intramolecular Aza-Diels–Alder Reactions, and DanceChemistry: A Visual Teaching Aid

  • Author(s): Tay, Gidget C.
  • Advisor(s): Rychnovsky, Scott D
  • et al.
Abstract

A modular synthesis of the reportedly potent molluscicide, cyanolide A, was developed to provide facile access to a series of cyanolide A analogues. The synthesis of strategic derivatives was initiated in order to determine the structural features of cyanolide A required for molluscicidal activity. Cyanolide A was synthesized in twelve steps with an overall 2% yield. After extensive SAR studies, it was found that cyanolide A was not responsible for the reported molluscicidal activity observed in the original studies.

A diastereoselective synthesis of cis-2,6-disubstituted tetrahydropyran-4-ones was developed. The key step of this methodology, a silyl enol ether Prins cyclization, was promoted by a condensation reaction between a hydroxy silyl enol ether and an aldehyde to afford substituted tetrahydropyran-4-ones. The cyclization was tolerant of many functional groups, and the modular synthesis of the hydroxy silyl enol ether allowed for the formation of more than thirty new tetrahydropyran-4-ones with up to 97% yield and >95:5 dr. The cyclization step forms new carbon–carbon and carbon–oxygen bonds, as well as a quaternary center with good diastereoselectivity. The method provides a versatile route for the synthesis of substituted tetrahydropyrans.

The scope and diastereoselectivity of an intramolecular aza-Diels–Alder reaction starting from a variety of 2-cyano-1-aza-1,3-butadienes was explored. The key reactions involved in synthesizing the Diels–Alder precursors are an imine condensation and a Strecker reaction and subsequent oxidation. The method provides a route for the synthesis of substituted quinolizidine and indolizidine heterocycles containing a cyanoenamine functional group.

A visual aid teaching tool, the DanceChemistry video series, has been developed to teach fundamental chemistry concepts through dance. These educational videos portray chemical interactions at the molecular level using dancers to represent chemical species. Students reported that the DanceChemistry videos helped them visualize chemistry ideas in a new and memorable way. Surveying the general laboratory course at the University of California, Irvine (n = 1266), 75% of the students said they wanted to use these videos to learn additional chemistry topics in the future. Data from pre- and post-surveys show an increase in students’ average scores after watching a five minute DanceChemistry video. These instructional videos are disseminated broadly through a dedicated YouTube channel, DanceChemistry.

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