Synthesis of β2,2-Amino Acids by Stereoselective Alkylation of Isoserine Derivatives Followed by Nucleophilic Ring Opening of Quaternary Sulfamidates

  1. Tovillas, Pablo 1
  2. Navo, Claudio D. 2
  3. Oroz, Paula 1
  4. Avenoza, Alberto 1
  5. Corzana, Francisco 1
  6. Zurbano, María M. 1
  7. Jiménez-Osés, Gonzalo 23
  8. Busto, Jesús H. 1
  9. Peregrina, Jesús M. 1
  1. 1 Universidad de La Rioja
    info

    Universidad de La Rioja

    Logroño, España

    ROR https://ror.org/0553yr311

  2. 2 Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 800, 48160 Derio, Spain
  3. 3 Ikerbasque, Fundación Vasca para la Ciencia
    info

    Ikerbasque, Fundación Vasca para la Ciencia

    Bilbao, España

Show affiliations +
Journal:
The Journal of Organic Chemistry

ISSN: 0022-3263,  1520-6904

Year of publication: 2022

Volume: 87

Issue: 13

Pages: 8730-8743

Type: Article

beta Ver similares en nube de resultados
DOI: 10.1021/ACS.JOC.2C01034 GOOGLE SCHOLAR lock_openOpen access editor

More publications in: The Journal of Organic Chemistry

Institutional repository: lock_openOpen access Editor

Abstract

Chiral bicyclic N,O-acetal isoserine derivatives have been synthesized by an acid-catalyzed tandem N,O-acetalization/intramolecular transcarbamoylation reaction between conveniently protected l-isoserine and 2,2,3,3-tetramethoxybutane. The delicate balance of the steric interactions between the different functional groups on each possible diastereoisomer controls their thermodynamic stability and hence the experimental product distribution. These chiral isoserine derivatives undergo diastereoselective alkylation at the α position, proceeding with either retention or inversion of the configuration depending on the relative configuration of the stereocenters. Quantum mechanical calculations revealed that a concave-face alkylation is favored due to smaller torsional and steric interactions at the bicyclic scaffold. This synthetic methodology gives access to chiral β2,2-amino acids, attractive compounds bearing a quaternary stereocenter at the α position with applications in peptidomimetic and medicinal chemistry. Thus, enantiopure α-alkylisoserine derivatives were produced upon acidic hydrolysis of these alkylated scaffolds. In addition, α-benzylisoserine was readily transformed into a five-membered ring cyclic sulfamidate, which was ring opened regioselectively with representative nucleophiles to yield other types of enantiopure β2,2-amino acids such as α-benzyl-α-heterofunctionalized-β-alanines and α-benzylnorlanthionine derivatives.

€ View funding

Funding information

Funders

Bibliographic References

  • 10.1002/chir.23103
  • Evans D. A., (2007), Asymmetric Synthesis-The Essentials, pp. 3
  • 10.1039/C6RA00653A
  • 10.1039/c0cc04629a
  • 10.1002/ejoc.200300452
  • 10.1002/chem.200601746
  • 10.1021/jo070656b
  • 10.1021/jo4019396
  • 10.1021/jo500015c
  • 10.1021/cr000045i
  • 10.1002/cbdv.200490087
  • 10.1039/C1CS15097A
  • 10.1021/ar800009n
  • 10.1080/00304940903376028
  • Juaristi E., (2005), Enantioselective Synthesis of β-Amino Acids, 10.1002/0471698482
  • 10.1021/jo048639z
  • 10.2174/0929867024606759
  • 10.1002/(SICI)1099-0690(200001)2000:1<1::AID-EJOC1>3.0.CO;2-6
  • Christoffers J., (2005), Quaternary Stereocenters, 10.1002/3527606858
  • 10.1002/anie.202009892
  • 10.1039/C9CC09239K
  • 10.1039/B400282B
  • 10.1021/acs.orglett.5b02927
  • 10.1021/acs.joc.7b03225
  • 10.1021/jo960170n
  • 10.1002/anie.196710461
  • 10.1021/acs.orglett.6b00840
  • 10.1039/C3SC52538D
  • 10.1002/anie.201205001
  • 10.1016/j.tetasy.2006.11.033
  • Baig R. B. N., (2015), Aldrichimica Acta, 48, pp. 71
  • 10.1021/ja011932l
  • 10.1021/ja9010628
  • 10.1021/acs.orglett.8b03254
  • 10.1021/acs.joc.7b02352
  • 10.1021/ol9013552
  • 10.1002/hlca.200490073
  • 10.1002/chem.201603910
  • 10.1021/ol703045z
  • 10.1055/s-0029-1218743
  • 10.1128/iai.25.3.775-780.1979
  • 10.1021/cr030105v
  • 10.1039/c1ob05946g
  • 10.1016/j.tetasy.2012.08.010
  • Frisch M. J., (2016), Gaussian 16
  • 10.1007/s00214-007-0310-x
  • 10.1063/1.3359469
  • 10.1021/jp205508z
  • 10.1063/1.456010
  • 10.1021/j100377a021
  • Sheldrick G. M., (1997), SHELXL97: Program for the Refinement of Crystal Structures
  • 10.1002/chir.22681
  • 10.1002/mrc.5062
  • Tovillas, P. Synthesis and reactivity of cyclic sulfamidates derived from amino acids. Ph.D. Dissertation, University of La Rioja, Logroño, La Rioja, Spain, 2021.