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Asymmetric synthesis of enantiomerically and diastereoisomerically enriched 4-[F or Br]-substituted glutamic acids

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Abstract

A novel simple synthetic protocol for the preparation of both (2S,4R)- and (2S,4S)-FGlu, applying Michael addition of methyl α-fluoroacrylate to a NiII complex of glycine Schiff base with BPB, was elaborated. In addition, same reaction of mentioned complex with ethyl α-bromoacrylate leads to the NiII complex of the Schiff base of BPB with (2S,4R)-4-bromo-glutamic acid monoester, that can be transformed into the corresponding complexes of 1-aminocyclopropane-1,2-dicarboxylic acid. The decomposition of the diastereoisomerically pure complexes leads to corresponding enantiomerically enriched (ee > 98%) amino acids.

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Scheme 1
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Abbreviations

Glu:

Glutamic acid

FGlu:

4-Fluoroglutamic acids

FDG:

2-Fluorodeoxyglucose

PET:

Positron emission tomography

BPB :

(S)-2-N-(N′-benzylprolyl)aminobenzophenone

Ni-BPB-Gly (1):

NiII complex of a Schiff’s base of BPB and glycine

AA:

Amino acid

d.r. :

Diastereomers ratio

de :

Diastereomeric excess

ee :

enantiomeric excess

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Acknowledgments

The authors thank Bayer Schering Pharma Aktiengesellschaft and RFBR (08-03-00466a) for financial support.

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Authors and Affiliations

  1. A. N. Nesmeyanov Institute of Organoelement Compounds Russian Academy of Science, B-334, Vavilova str. 28, Moscow, 119991, Russia

    Yuri N. Belokon, Victor I. Maleev, Tatiana F. Savel’eva, Margarita A. Moskalenko, Dmitri A. Pripadchev & Victor N. Khrustalev

  2. Chemistry Department, Chair of Pharmaceutical Chemistry, Yerevan State University, Manukyan str. 1, 0049, Yerevan, Armenia

    Ashot S. Saghiyan

Authors
  1. Yuri N. Belokon
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  2. Victor I. Maleev
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  3. Tatiana F. Savel’eva
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  4. Margarita A. Moskalenko
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  5. Dmitri A. Pripadchev
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  6. Victor N. Khrustalev
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  7. Ashot S. Saghiyan
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Corresponding author

Correspondence to Yuri N. Belokon.

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Experimental data available free of charge in the supplementary section.

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Belokon, Y.N., Maleev, V.I., Savel’eva, T.F. et al. Asymmetric synthesis of enantiomerically and diastereoisomerically enriched 4-[F or Br]-substituted glutamic acids. Amino Acids 39, 1171–1176 (2010). https://doi.org/10.1007/s00726-010-0551-1

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