Abstract
A divergent synthetic strategy starting from a common trans-oxazolidine dicarboxylate intermediate has been successful to produce several non-proteinogenic l-threo-β-hydroxyaspartate derivatives efficiently with high stereoselectivity. Three bioactive α-amino-β-hydroxy acids, l-threo-β-hydroxyaspartic acid, l-threo-β-hydroxyasparagine, and l-threo-β-benzyloxyaspartic acid, were synthesized in good yields (58–83%) from the common chiral intermediate, and the chemoselective peptide bond formation at the α-amino group, β-hydroxy group, or α-carboxylic acid of the common intermediate was possible to afford the corresponding dipeptide, tripeptide, or didepsipeptide intermediate in 46~77% yields (in three-to-four steps) due to the orthogonal protective groups on the chiral intermediate.
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Abbreviations
- l-tHyAsp:
-
L-threo-β-Hydroxyaspartic acid
- l-tHyAsn:
-
L-threo-β-hydroxyasparagine
- PhSO2CH2NO2 :
-
Phenylsulfonylnitromethane
- TBS:
-
t-Butyldimethylsilyl
- TBAF:
-
Tetrabutylammonium fluoride
- l-TBOA:
-
L-threo-β-benzyloxyaspartic acid
- N-Boc-l-Val:
-
N-Boc protected l-valine
- l-Leu-OMe:
-
L-leucine methyl ester
- EDC:
-
1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide
- TLC:
-
Thin-layer chromatography
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Acknowledgements
We would like to thank the BK-21 Four Program, the Fundamental R&D Program for Core Technology of Materials funded by the Ministry of Knowledge Economy for financial support. This work was also supported by a grant from the Institute of Chemical Processes at Seoul National University.
Funding
This work was financially supported by the BK-21 Four Program, the Fundamental R&D Program for Core Technology of Materials funded by the Ministry of Knowledge Economy.
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Lee, Y., Seo, Y., Lee, B. et al. Divergent synthesis of biologically active l-threo-β-hydroxyaspartates from common trans-oxazolidine dicarboxylate. Amino Acids 54, 1601–1610 (2022). https://doi.org/10.1007/s00726-022-03196-8
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DOI: https://doi.org/10.1007/s00726-022-03196-8