Stereospecific cyclization strategies for α,ε-dihydroxy-β-amino esters: asymmetric syntheses of imino and amino sugars

J Org Chem. 2014 Oct 17;79(20):9686-98. doi: 10.1021/jo5018298. Epub 2014 Sep 30.

Abstract

A range of biologically significant imino and amino sugars [1,4-dideoxy-1,4-imino-D-allitol, 3,6-dideoxy-3,6-imino-L-allonic acid, (3R,4S)-3,4-dihydroxy-L-proline, 1,5-anhydro-4-deoxy-4-amino-D-glucitol, and 1,5-anhydro-4-deoxy-4-amino-L-iditol] has been prepared via stereospecific cyclization of α,ε-dihydroxy-β-amino esters. These substrates are readily prepared via conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide to enantiopure α,β-unsaturated esters (β-substituted with cis- and trans-dioxolane units) coupled with in situ enolate oxidation with camphorsulfonyloxaziridine (CSO). Activation of the ε-hydroxyl group allowed cyclization to either the corresponding pyrrolidine or the tetrahydropyran scaffold, with the course of the cyclization process being dictated by the relative configuration of the dioxolane unit. When the α,ε-dihydroxy-β-amino ester bears a cis-dioxolane unit, cyclization occurs upon attack of the β-amino substituent to give the corresponding pyrrolidine after in situ N-debenzylation. In contrast, when the α,ε-dihydroxy-β-amino ester bears a trans-dioxolane unit, cyclization occurs upon attack of the α-hydroxyl substituent to give the corresponding tetrahydropyran.

MeSH terms

  • Amino Sugars / chemical synthesis*
  • Amino Sugars / chemistry
  • Crystallography, X-Ray
  • Cyclization
  • Esters
  • Imines / chemical synthesis*
  • Imines / chemistry
  • Lithium / chemistry*
  • Molecular Structure
  • Oxidation-Reduction
  • Proline / chemical synthesis*
  • Pyrans / chemistry*
  • Stereoisomerism

Substances

  • Amino Sugars
  • Esters
  • Imines
  • Pyrans
  • Proline
  • Lithium