New building block for polyhydroxylated piperidine: total synthesis of 1,6-dideoxynojirimycin

J Org Chem. 2008 Apr 4;73(7):2898-901. doi: 10.1021/jo702480y. Epub 2008 Mar 12.

Abstract

(3R,4S)-3-Hydroxy-4-N-allyl-N-Boc-amino-1-pentene 10, an important precursor for the synthesis of polyhydroxylated piperidines, has been achieved as a single diastereomer without racemization via vinyl Grignard addition to N-Boc-N-allyl aminoaldehyde 9, which was derived from an enantiopure natural amino acid. Having forged a tetrahydropyridine ring scaffold 13 from 10 in 85% yield via RCM using Grubbs II catalyst, we were able to effect its stereodivergent dihydroxylation, via a common epoxide intermediate to yield a range of interesting hydroxylated piperidines, including ent-1,6-dideoxynojirimycin (ent-1,6-dDNJ) 1 (28% overall yield) and 5-amino-1,5,6-trideoxyaltrose 2 (29% over all yield) in excellent dr. To the best of our knowledge, our synthesis of ent-1,6-dDNJ 1 is the most expeditious to date.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Deoxynojirimycin / analogs & derivatives*
  • 1-Deoxynojirimycin / chemical synthesis
  • 1-Deoxynojirimycin / chemistry
  • Hydroxylation
  • Molecular Conformation
  • Piperidines / chemical synthesis*
  • Piperidines / chemistry
  • Stereoisomerism

Substances

  • 1,6-dideoxynojirimycin
  • Piperidines
  • 1-Deoxynojirimycin