Photochemical Cycloaddition as a Gateway to Bicyclic Lactones: Toward Tricyclic Iridoid-Inspired Scaffolds
- 1 Department of Chemistry and Physical Sciences, Nicholls State University, Thibodaux, Louisiana, USA
- 2 Department of Chemistry and Physical Sciences, Nicholls State University, Thibodaux, Louisiana, USA
Abstract
A photochemical [2+2] cycloaddition between cyclopentene-1-one and 1,1-dimethoxyethylene was effectively utilized to synthesize a key bicyclic intermediate in the preparation of tricyclic iridoid-inspired scaffolds. The regioselective outcome of the cycloadduct was confirmed through ¹H NMR and subsequent chemical reactivity studies, indicating that the methoxy groups do not occupy positions β to the carbonyl. Following this, hydrolysis of the cycloadduct yielded a diketone in an excellent yield of 85%, which was subsequently subjected to Baeyer-Villiger oxidation, resulting in a fused γ -lactone with a yield of 64%. Structural elucidation of the intermediates and the final product was conducted using NMR, IR, and mass spectrometry techniques. This photochemical synthetic pathway offers a concise approach to bioinspired tricyclic architectures that may hold significance in natural product chemistry and the design of neuroactive compounds.
- Li, Y.S., Matsunaga, K., Ishibashi, M. and Ohizumi, Y. (2001) Littoralisone, a Novel Neuritogenic Iridolactone Having an Unprecedented Heptacyclic Skeleton from Verbena littoralis . The Journal of Organic Chemistry , 66, 2165-2167.
- Zhao, Y., Wang, J. and Wang, Y. (2020) Recent Advances in Iridoid Chemistry: Biosynthesis and Chemical Synthesis. Chemistry — An Asian Journal , 15, 4073-4085.
- Zhou, J. and Wang, H. (2020) Iridoids: Research Advances in Their Phytochemistry, Biological Activities, and Pharmacokinetics. Frontiers in Pharmacology , 11, Article ID: 879.
- Makama, B. (2012) Stereoselective Synthesis of Bicyclic Lactones via Annelation Protocol. American Journal of Organic Chemistry , 2, 127-131. https://doi.org/10.5923/j.ajoc.20120206.01
- Makama, B.Y. (2010) Preparation of Bicyclic Lactones Using Lewis Acids Catalyzed Ene-Reaction. Science World Journal , 5, 15-16. https://doi.org/10.4314/swj.v5i2.61508
- Zimmerman, H.E. and Mariano, P.S. (1996) Photochemical [2+2] Cycloaddition Reactions of Ketenes and Enones: Mechanisms and Synthetic Applications. Chemical Reviews , 96, 123-140.
- Ischay, M.A., Anzovino, M.E., Du, J. and Yoon, T.P. (2008) Efficient Visible Light Photocatalysis of [2+2] Enone Cycloadditions. Journal of the American Chemical Society , 130, 12886-12887. https://doi.org/10.1021/ja805387f
- Corey, E.J., Bass, J.D., LeMahieu, R. and Mitra, R. (1964) A New Stereospecific Synthesis of Bicyclic Lactones. Journal of the American Chemical Society , 86, Article 5570.
- Perrin, D.D. and Armarego, W.L.F. (1998) Purification of Laboratory Chemicals. 4th Edition, Pergamon Press.
- Termont, D., De Keukeleire, D.D. and Vandewalle, M. (1977) Photochemical Reaction of Cyclopentenone Derivatives. Journal of the Chemical Society , Perkin Transacti ons 1, 10, 2349-2356.