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CC BY 4.0 · Pharmaceutical Fronts 2023; 05(03): e168-e174
DOI: 10.1055/s-0043-1772224
Original Article

A Short and Facile [2 + 2] Photocycloaddition Protocol Toward Construction of a Levuglandin Skeleton

Pradeep T. Deota
1   Department of Applied Chemistry, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Baroda, Gujarat, India
,
Deepak Singh
2   Department of Chemical Sciences, University of Padova, Padova, Italy
,
Gaurang J. Bhatt
1   Department of Applied Chemistry, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Baroda, Gujarat, India
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Abstract

The γ-ketoaldehyde functionality of levuglandins (LGs) has a great propensity for various diseases such as Alzheimer's, atherosclerosis, and renal diseases. The synthesis of LGs constitutes a challenge for synthetic organic chemists due to their complex structures and low abundance in nature which has prompted us to develop its quick synthesis. This study aimed to explore a novel route for the construction of a levuglandin skeleton. We envisaged that the photocycloaddition of an appropriate alkene with equivalent propyne would give the cyclobutene adduct. The oxidative cleavage of the photocycloadduct can lead to the formation of the keto-aldehyde functionality. In this study, the readily available isopropenyl acetate (5) and methyl oleate (6) were used as starting materials to synthesize the target compound 13. The key step involves photocycloaddition of compounds 5 and 6, a regio-controlled elimination of the hydroxy group of compound 10, forming a cyclobutene derivative, as well as an oxidative cleavage of the cyclobutene derivative gives the framework of levuglandin. The intriguing chemistry of elimination resulting in the inseparable mixture of regioisomeric cyclobutenes has also been discussed. The route was simple and economical and helped for the creation of γ-ketoaldehyde functionality which is vital for the activity of levuglandins and can be extended for the construction of prostanoid skeleton through aldol condensation of the γ-ketoaldehydes.

Keywords

levuglandins - photocycloaddition - γ-ketoaldehydes

Supporting Information

1H NMR, 13C NMR, mass, and IR spectra of compounds 7 (or 8), 9, 10, 11, and 14 (mixed), 12, and 13 are available in the Supporting Information (Figs. S1–S28 [online only])002E


Supplementary Material



Publication History

Received: 03 February 2023

Accepted: 11 July 2023

Article published online:
24 August 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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