From Cyclic Peptoids to Peraza-macrocycles: A General Reductive Approach

Abstract

Peraza-macrocycles form chelates of high thermodynamic and kinetic stability useful in diagnostic imaging (MRI, SPECT, PET), in coordination chemistry, and as catalysts. In this letter, we report an advantageous method to prepare these compounds via BH 3 -induced reduction of cyclic peptoids. Using this procedure, 10 homo-and heterosubstituted aza-coronands, with different sizes and side chains, have been synthesized from the corresponding cyclic oligoamides. Solid structures of free, protonated, and Na + coordinated polyaza-derivatives have been disclosed by singlecrystal X-ray diffraction analysis.

1,2,3‐Triazole‐Containing Azamacrocycles from Chiral Triazolopeptoids: Synthesis and Solid‐State Studies

“…[5] Recently we reported an efficient reductive route from cyclic peptoids, a valuable class of peptidomimetics, [6][7][8][9] to differently decorated peraza-macrocycles. [10] This synthetic strategy yields an ample variety of homo-and hetero-substituted azacoronands [10,11] and does not require low-yield regioselective post synthetic modifications or intricate protecting group manipulations, as in the classic synthetic approaches. [10] In our ongoing research on macrocyclic peptoids we recently reported a new class of "extended" peptoids (1-3).…”

“…[10] This synthetic strategy yields an ample variety of homo-and hetero-substituted azacoronands [10,11] and does not require low-yield regioselective post synthetic modifications or intricate protecting group manipulations, as in the classic synthetic approaches. [10] In our ongoing research on macrocyclic peptoids we recently reported a new class of "extended" peptoids (1-3). [12] These derivatives present, into oligoamide peptoid backbone, aromatic spacers which confer peculiar conformational features and metal chelating properties.…”

The Challenge of Conformational Isomerism in Cyclic Peptoids

“…In more than ten years from the brilliant work by Kent Kirshenbaum and co‐workers, cyclic peptoids gained the status of key bioactive/biomimetic agents, efficient catalysts, promising supramolecular building‐blocks, and rigid scaffold/topological templates …”

Macrocyclic Triazolopeptoids: A Promising Class of Extended Cyclic Peptoids

“…), scant synthetic effort has been devoted to sequence-defined oligomerization processes . A modular accretion of bifunctional monomers is instead adopted for the synthesis of cyclic peptoids (cyclic oligomers of N-substituted glycines), , a growing class of biomimetic compounds with enormous potential in catalysis, in material chemistry, as bioactive agents, , and as precursors of azamacrocycles . The versatility of their synthetic method allows ample structural flexibility and facile introduction of rigid aromatic spacers into the peptoid oligoamide backbone, producing the valuable “extended peptoids”, , with excellent conformational properties , (despite the absence of intramolecular H-bonding) and metal chelating abilities …”