Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of N-phosphinylimines

Jian-bo Xie, Jian Luo, Timothy R. Winn, David B. Cordes, Guigen Li*

*Corresponding author for this work

Research output: Contribution to journalLetterpeer-review

35 Citations (Scopus)

Abstract

A new approach to the anticancer drug Velcade was developed by performing asymmetric borylation of an imine anchored with a chiral N-phosphinyl auxiliary. Throughout the 7-step synthesis, especially in the imine's synthesis and in the asymmetric borylation reactions, operations and work-up were conducted in simple and easy ways without any column chromatographic purification, which defines the GAP (group-assisted purification) chemistry concept. It was found that the optically pure isomer (dr > 99: 1) can be readily obtained by washing the crude mixture of the asymmetric borylation reaction with hexane; the chiral N-phosphinyl auxiliary can be easily recovered after deprotection is finished. Several other N-phosphinylimines were also investigated for the asymmetric borylation reaction. The absolute configuration of the borylation product was confirmed by single crystal X-ray diffraction analysis.

Original languageEnglish
Pages (from-to)746-751
Number of pages6
JournalBeilstein Journal of Organic Chemistry
Volume10
DOIs
Publication statusPublished - 31 Mar 2014

Keywords

  • Asymmetric borylation
  • GAP chemistry
  • Organophosphorous
  • N-phosphinylimine
  • Velcade
  • Imine chemistry
  • Boronic acids
  • Amino-acids
  • Chymotrypsin
  • Inhibitors
  • Elastase
  • Esters
  • Hydroboration
  • Aldehydes
  • Reagents

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