Differential Peptide Multi‐Macrocyclizations at the Surface of a Helical Foldamer Template

Abstract

Hybrid sequences comprising a peptide with several Cys residues and an aromatic foldamer helix with several chloroacetamide functions at its surface were synthesized. Such products may in principle form numerous macromulticyclic thioether products by intramolecularly combining all Cys residues and all chloroacetamide functions. However, we show that the reactive sites on the structurally defined helix can be placed at such locations that the peptide selectively stitches itself to form a series of different macrocycles within mostly one preferred product. Reactions were monitored by HPLC and products with two, three or four macrocycles were identified using LC-MS and NMR. The series of selective macrocyclizations define a sort of reaction trail where reaction sites otherwise identical are involved successively because of their precise positioning in space. The trails can be predicted to a large extent based on structural considerations and the assumption that smaller macrocycles form faster.

Conformation Governed Reactivity of Fused Thia-Sapphyrin Dimers Bearing Multiply Fused Heteroaromatic Rings

“…Considering the presence of a meso-sp 3 CH in 1, it was treated with common oxidants to check whether it can be oxidized to fully conjugated molecules. 28,32 Interestingly, heating 1 in N,N-dimethylformamide (DMF) under aerobic conditions afforded three fused dimeric species, 2 anti , 2 syn , and 3, in yields of 46%, 1.5%, and 4%, respectively.…”

“…Multiple scientific communities are interested in mimicking and surpassing their distinctive properties. [1][2][3] For various natural systems, suitable conformations and proper alignment of the macrocycles often play key roles in their chemical reactivities and physicochemical properties. [4][5][6][7] However, because of synthetic difficulties, the structure-property correlation has not been fully revealed due to the lack of proper artificial macrocycle prototypes.…”