Evidence for Ion-Templation During Macrocyclooligomerization of Depsipeptides

J Am Chem Soc. 2018 Apr 4;140(13):4560-4568. doi: 10.1021/jacs.7b13148. Epub 2018 Mar 22.

Abstract

The ion-mediated Mitsunobu macrocyclooligomerization (M-MCO) reaction of hydroxy acid depsipeptides provides small collections of cyclic depsipeptides with good mass recovery. The approach can produce good yields of a single macrocycle or provide rapid access to multiple oligomeric macrocycles in good overall yield. While Lewis acidic alkali metal salts are known to play a role in the outcome of MCO reactions, it is unclear whether their effect is due to an organizational (e.g., templating) mechanism. Isothermal titration calorimetry (ITC) was used to study macrocycle-metal ion binding interactions, and this report correlates these thermodynamic measurements to the (kinetically determined) size distributions of depsipeptides formed during a Mitsunobu-based macrocyclooligomerization (MCO). Key trends have been identified in quantitative metal ion-cyclic depsipeptide binding affinity ( Ka), enthalpy of binding (Δ H), and stoichiometry of complexation across discrete series of macrocycles, and they provide the first analytical platform to rationally select a metal-ion template for a targeted size regime of cyclic oligomeric depsipeptides.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Calorimetry
  • Cyclization
  • Depsipeptides / chemistry*
  • Kinetics
  • Molecular Structure
  • Thermodynamics

Substances

  • Depsipeptides