An optimized method for an (2R,3S)-isocitric acid building block

Abstract

An optimized method for (2R,3S)-isocitric acid lactone-2,3-dicarboxylic acid dimethyl ester as an (2R,3S)-isocitric acid building block based on a fermentation solution containing both (2R,3S)-isocitric acid (ICIT) and citric acid is described. The number of operations needed until now has been reduced; some steps have been modified, making altogether the method distinctly faster. During the course of this investigation, crystal structures have been determined of (2R,3S)-isocitric acid lactone-2,3-dicarboxylic acid dimethyl ester, (2R,3S)-isocitric acid lactone-2,3-dicarboxylic acid, and (2R,3S)-isocitric acid lactone-2,3-dicarboxylic acid anhydride. For the first time, full NMR data are given for ICIT trimethyl ester and ICIT lactone-2,3-dicarboxylic acid dimethyl ester. The multigram amounts of the three ICIT lactone compounds open the way for the synthetic use of ICIT generated in a biotechnological process.

Graphical abstract

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3

References

  1. 1.

    Heretsch P, Thomas F, Aurich A, Krautscheid H, Sicker D, Giannis A (2008) Angew Chem Int Ed 47:1958

    CAS  Article  Google Scholar 

  2. 2.

    Kamzolova SV, Shamin RV, Stepanova NN, Morgunov GI, Lunina JN, Allayarov RK, Samoilenko VA, Morgunov IG (2018) BioMed Res Int 2018:2543210

    Article  Google Scholar 

  3. 3.

    Moore GL, Stringham RW, Teager DS, Yue TY (2017) Org Process Res Dev 21:98

    CAS  Article  Google Scholar 

  4. 4.

    Aurich A, Hofmann J, Oltrogge R, Wecks M, Gläser R, Blömer L, Mauersberger S, Müller RA, Sicker D, Giannis A (2017) Org Process Res Dev 21:866

    CAS  Article  Google Scholar 

  5. 5.

    Sheldrick GM (2008) Acta Cryst A 64:112

    CAS  Article  Google Scholar 

  6. 6.

    STOE & Cie GmbH (2018) X-Area 1.82. Darmstadt, Germany

  7. 7.

    Brandenburg K (2014) Diamond 3.2k. Bonn, Germany

Download references

Acknowledgements

We are grateful to Katrin Hoffmann and Tamara Meinel for their unimpeachable support with NMR measurements throughout many years. We thank Prof. Dr. Joachim Sieler for his continuous support of our investigations.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Dieter Sicker.

Additional information

Dedicated to Prof. Dr. Athanassios Giannis on the occasion of his 65th birthday.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Bullin, K., Hennig, L., Herold, R. et al. An optimized method for an (2R,3S)-isocitric acid building block. Monatsh Chem 150, 247–253 (2019). https://doi.org/10.1007/s00706-018-2319-3

Download citation

Keywords

  • Bioorganic chemistry
  • Separation
  • Optimization
  • Carboxylic acids
  • Isomers
  • Crystal structure