Spiroligomer

Spiroligomer molecules (also known as bis-peptides) are synthetic oligomers made by coupling pairs of bis-amino acids into a fused ring system.

[1] Spiroligomer molecules are rich in stereochemistry and functionality because of the variety of bis-amino acids that are capable of being incorporated during synthesis.

[2] Due to the rigidity of the fused ring system,[3] the three-dimensional shape of a Spiroligomer molecule – as well as the display of any functional groups – can be predicted, allowing for molecular modeling and dynamics.

Spiroligomer molecules are synthesized in a step-wise approach by adding a single bis-amino acid at each stage of the synthesis.

[7] The second Spiroligomer catalyst accelerated an aromatic Claisen rearrangement with a catalytic dyad similar to that found in ketosteroid isomerase.

Spiroligomer scaffolds
Spiroligomer Scaffolds - (A) bis-amino acids (B) 3D Mock up of a bis-amino acids (C) Spiroligomer Trimer (D) 3D Mock up of a Spiroligomer
Synthesis of Spiroligomer building blocks (bis-amino acids)
Synthesis of Spiroligomer building blocks (bis-amino acids). (a) Cbz-Cl, NaHCO3, 1:10 dioxane/water (b) Jones reagents, acetone, 0 oC to rt; (c) Isobutylene, H2SO4 (cat.), CH2Cl2, 0 oC to rt; (d) (NH4)2CO3, KCN, 1:1 EtOH/water, sealed tube; (e) (i) AcOH/Ac2O, Reflux; (ii) 2M HCl, reflux; (iii) Recrystallization
Shown are three common ways of connecting Spiroligomer molecules through pairs of amide bonds (diketopiperazines, DKPs)
Shown are three common ways of connecting Spiroligomer molecules through pairs of amide bonds (diketopiperazines, DKPs)
Transesterification of vinyl-trifluoroacetate with a Spiroligozyme
Transesterification of vinyl-trifluoroacetate with a Spiroligozyme
Aromatic Claisen Rearrangement with a Spiroligozyme
Aromatic Claisen Rearrangement with a Spiroligozyme
Chemdraw of a Spiroligomer that penetrates cells and binds HDM2
Chemdraw of a Spiroligomer that penetrates cells and binds HDM2
A spiroligomer that binds manganese and zinc
A Spiroligomer that binds manganese and zinc