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. 2025 Jul 18;90(28):10064-10073.
doi: 10.1021/acs.joc.5c01306. Epub 2025 Jul 5.

Sustainable Photocatalytic Synthesis of Glitazones via Riboflavin Tetraacetate

Sarah Jane Rezzi  1 , Marco Koten  1 , Rita Maria Concetta Di Martino  1 , Gianluca Papeo  2 , Tracey Pirali  1 , Marina Caldarelli  2
Affiliations

Sustainable Photocatalytic Synthesis of Glitazones via Riboflavin Tetraacetate

Sarah Jane Rezzi et al. J Org Chem. .

Abstract

A more sustainable and versatile method to access antidiabetic glitazones is demanded. Herein, we report the unprecedented photocatalytic coupling of N-protected methylene thiazolidinediones with radical precursors (organoborates or carboxylic acids) under riboflavin tetraacetate catalysis. The methodology accepts various functional groups and affords (Het)Ar-(CH2)n-thiazolidinediones by transition-metal-free organic photoredox catalysis under mild conditions. The applicability of the developed protocol is showcased by the three-step preparation of the antidiabetic pioglitazone drug.

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Figures

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Representative glitazone drugs and synthetic approaches to (Het)­Ar–CH2–TZD.
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1. Proof-of-Concept Synthesis of Glitazone Derivative 6
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2. Possible Mechanism for the Formation of 1 and 2
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Scope of the reaction.
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Deprotection of N-tert-butyl glitazones.
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3. Synthesis of Pioglitazone
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Plausible reaction mechanism and deuterium incorporation.
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