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Synthesis of novel adamantyl and homoadamantyl-substituted \(\beta \)-hydroxybutyric acids

Abstract

Several new adamantyl and homoadamantyl-substituted \(\beta \)-hydroxybutyric acids, 2-[2-(1-adamantyl)ethyl]-3-hydroxybutyric acid (2), 2-(3-homoadamantyl)-3-hydroxybutyric acid (3), and 2-(1-homoadamantyl)-3-hydroxybutyric acid (4), analogues of the 2-(1-adamantyl)-3-hydroxybutyric acid (1), have been prepared as mixtures of diastereoisomers using selective reduction of corresponding \(\beta \)-keto esters or aldol condensation of the corresponding carboxylic acid and acetaldehyde. The rearrangement of adamantylmethyl and 3-homoadamantyl groups provided entry to both 3-homoadamantyl and 1-homoadamantyl-substituted hydroxy acids 3 and 4, respectively. The relative configurations of diastereoisomers 3 and 4 have been determined by NMR spectroscopy comparing the values of coupling constants. Adamantyl-substituted \(\beta \)-hydroxybutyric acid 2 has also been prepared in enantiomerically pure form by Evan’s asymmetric synthesis and the absolute configuration has been determined by X-ray crystallography. Contrary to the long-chain acid 2, the attempt to prepare short-chain hydroxy acids 1 and 4 by the same method failed indicating pronounced sensitivity of the used method to the vicinity of the bulky cage group.

Graphical Abstract

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Acknowledgments

We thank to the Ministry of Science Education and Sports of the Republic of Croatia (Grant No. 098-0982933-2911, KMM) and to HAZU (Grant awarded to M. Matković) for financial support.

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Correspondence to Kata Mlinarić-Majerski.

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Matković, M., Vukelić, S., Cirimotić, R. et al. Synthesis of novel adamantyl and homoadamantyl-substituted \(\beta \)-hydroxybutyric acids. Mol Divers 17, 817–826 (2013). https://doi.org/10.1007/s11030-013-9481-7

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Keywords

  • Adamantyl
  • \(\beta \)-Keto ester
  • \(\beta \)-Hydroxybutyric acid
  • Homoadamantyl
  • Hydroxy acids
  • Rearrangement