Scientists from the ZIOC have proposed a new method for the preparation of chiral 2,4-dihydroxycarboxylic acids

Structural fragments of chiral 2,4-dihydroxycarboxylic acids and their derivatives (in particular, α-hydroxy-γ-lactones) are found in many natural compounds and pharmaceuticals. Enantiomerically enriched 2,4-dihydroxycarboxylic acids are usually prepared by the asymmetric aldol reaction of ethyl glyoxylate with aldehydes in the presence of a chiral catalyst.

Scientists of the I.N. Nazarov Laboratory of Fine Organic Synthesis of the Zelinsky Institute proposed a fundamentally new approach to the stereoselective synthesis of 2,4-dihydroxycarboxylic acids. The method is based on the involvement of stable and easy-to-handle aldehydes of the 3-hydroxypyranone series in the enantioselective catalytic aldol reaction instead of ethylglyoxylate. The resulting enantiomerically enriched heterocyclic aldols can easily be transformed into 2,4-dihydroxycarboxylic acids by oxidative fragmentation. The developed approach was used by researchers for the asymmetric synthesis of pantolactones, intermediate products for obtaining biologically active substances, and dexpanthenol, a drug for the treatment of dermatological diseases. The target structures were obtained in high yields and an enantioselectivity of 96% ee.

Source:

Maxim V. Smirnov, Alexander S. Kucherenko, Ilya D. Gridnev, Alexander A. Korlyukov, Sergei G. Zlotin γ-Pyronecarbaldehyde-Based Practical Asymmetric Catalytic Synthesis of Chiral 2,4-Dihydroxycarboxylic Acids and α-Hydroxy-γ-lactones // Adv. Synth. Catal., 2022, 364, 3245-3262. DOI: 10.1002/adsc.202200859.