Stereoselective Synthesis and Biological Activity of β-and α-D-Arabinose 1,5-Diphosphate: Analogues of a Potent Metabolic Regulator

Bruce E. Maryanoff, Allen B. Reitz, Gene F. Tutwiler, Stephen J. Benkovic, Patricia A. Benkovic, Simon J. Pilkis

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Abstract

The new compounds β- and a-D-arabinose 1,5-diphosphate (2 and 3) were prepared in a stereoselective manner as analogues of β-D-fructose 2,6-diphosphate (1), a potent regulator of glycolysis and gluconeogenesis. The synthetic routes toward both 2 and 3 originated from protected arabinose 4. Selective manipulation of protecting groups led to intermediates that allowed stereoselective (>85%) introduction of the phosphoryl functionality from the β (92%) or α (86%) face of the furanose, furnishing highly enriched 2 or 3. Unmasking of three pairs of varied protecting groups in the final step of each synthesis was accomplished with lithium in liquid ammonia. Compound 2 exhibits biological activity analogous to 1; i.e., it inhibits fructose 1,6-bisphosphatase and activates 6-phosphofructo-l-kinase; 3 only shows activation of the latter enzyme.

Original languageEnglish (US)
Pages (from-to)7851-7853
Number of pages3
JournalJournal of the American Chemical Society
Volume106
Issue number25
DOIs
StatePublished - Dec 1 1984

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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