A Simple Synthesis of Polyfunctionalized 4-Aminopyrazolidin-3-ones as ‘Aza-deoxa’ Analogs of D-Cycloserine

Authors

  • Ana Novak,

    1. Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, SI-1000 Ljubljana (phone: +386-1-2419254; fax: +386-1-2419220)
    Search for more papers by this author
  • Matej Štefanič,

    1. Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, SI-1000 Ljubljana (phone: +386-1-2419254; fax: +386-1-2419220)
    Search for more papers by this author
  • Uroš Grošelj,

    1. Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, SI-1000 Ljubljana (phone: +386-1-2419254; fax: +386-1-2419220)
    Search for more papers by this author
  • Martina Hrast,

    1. Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana
    Search for more papers by this author
  • Marta Kasunič,

    1. Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, SI-1000 Ljubljana (phone: +386-1-2419254; fax: +386-1-2419220)
    Search for more papers by this author
  • Stanislav Gobec,

    1. Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana
    Search for more papers by this author
  • Branko Stanovnik,

    1. Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, SI-1000 Ljubljana (phone: +386-1-2419254; fax: +386-1-2419220)
    2. Centre of Excellence EN-FIST, Trg osvobodilne fronte 13, SI-1000 Ljubljana
    Search for more papers by this author
  • Jurij Svete

    Corresponding author
    1. Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, SI-1000 Ljubljana (phone: +386-1-2419254; fax: +386-1-2419220)
    2. Centre of Excellence EN-FIST, Trg osvobodilne fronte 13, SI-1000 Ljubljana
    • Centre of Excellence EN-FIST, Trg osvobodilne fronte 13, SI-1000 Ljubljana

    Search for more papers by this author

Abstract

A simple five-step synthesis of fully substituted (4RS,5RS)-4-aminopyrazolidin-3-ones as analogs of D-cycloserine was developed. It comprises a two-step preparation of 5-substituted (4RS,5RS)-4-(benzyloxycarbonylamino)pyrazolidin-3-ones, reductive alkylation at N(1), alkylation of the amidic N(2) with alkyl halides, and simultaneous hydrogenolytic deprotection/reductive alkylation of the primary NH2 group. The synthesis enables an easy stepwise functionalization of the pyrazolidin-3-one core with only two types of common reagents, aldehydes (or ketones) and alkyl halides. The structures of products were elucidated by NMR spectroscopy and X-ray diffraction.

Ancillary