Gas-Phase Enantioselectivity of Chiral N-Linked Peptidoresorc[4]arene Isomers toward Dipeptides

Abstract

The gas-phase enantioselectivity of cone N-linked peptidoresorc[4]arenes (generally symbolized as M) toward the homologue dipeptides (generally symbolized as A) has been evaluated by measuring the kinetics of the A release from the diastereomeric [M x H x A](+) complexes induced by (R)-(-)-2-butylamine (B). In most cases investigated, the heterochiral [M x H x A](+) complexes, namely those wherein the configuration of the A guest is opposite to that of the host M pendants, react faster (up to 5 times) than the homochiral analogues, wherein guest A guest has the same configuration of the host M pendants. The kinetic results, discussed in the light of previous MS and NMR evidence, indicate that both the efficiency and the enantioselectivity of the guest exchange reaction depend essentially on the structure and the relative stability of the diastereomeric [M x H x A](+) complexes. These, in turn, depend on the functional groups and the configuration of both the guest and the host pendants. The absence of any significant effects of the B configuration indicates that, in all systems investigated, the dipeptide guest A is predominantly located outside the host chiral cavity.

Enantioselective supramolecular devices in the gas phase. Resorcin[4]arene as a model system

“…These preliminary results motivated the gas-phase enantioselectivity study reported in [43], in which the guest displacement between proton-bound diastereomeric [ M ∙H∙G] + ( M : I – IV ; G = 1 – 3 ) complexes and ( R )-(−)-2-butylamine (B) (Eq. 5 and Eq.…”

“…The resorcin[4]arene octamethyl ethers were functionalized with leucyl-valine and valyl-leucine ( I and III ; Scheme 1) methyl esters, and the enantioselectivity toward the same dipeptide esters used in their synthesis, namely, leucyl-valine-OMe and valyl-leucine-OMe ( 1 and 3 ; Scheme 1) was investigated [43]. …”

“…5 and Eq. 6 [43], thus suggesting that the amine does not need to enter the cavity to interact with the chiral lower portion of the host before displacing the dipeptide G from the complex. This hypothesis agrees well with the external location of G in the [ M ∙H∙G] + complex that was observed in independent solution experiments [44].…”

“…5 and Eq. 6 are appreciably affected by the nature of the –CO 2 R function of the dipeptidic guest, while they are not subject to the influence of the specific ester functions of the host pendants [43], thus, providing further evidence that the guest is placed outside the host cavity in [ M ∙H∙G] + ( M = I – III) . The negligible effect observed between [ IV ∙H∙G] + fast and their [ III ∙H∙G] + analogues (G = 1 , 3 ) was correlated to a similar spatial arrangement of the guests with respect to their receptors, while the relatively slow population of [ IV ∙H∙G] + (G = 1 , 3 ) reacts with an efficiency that is definitely lower than [ III ∙H∙G] + .…”

“…The negligible effect observed between [ IV ∙H∙G] + fast and their [ III ∙H∙G] + analogues (G = 1 , 3 ) was correlated to a similar spatial arrangement of the guests with respect to their receptors, while the relatively slow population of [ IV ∙H∙G] + (G = 1 , 3 ) reacts with an efficiency that is definitely lower than [ III ∙H∙G] + . This diverging behavior suggests that the guest in [ IV ∙H∙G] + slow is arranged in a completely different orientation, and this particular feature is due to the presence of the COOH tail in IV pendants, which acts as a protonated “hook” for dipeptides [43]. Indeed, the reaction enantioselectivity factors reflect these differences ([ M ∙H∙G] + ( M = I–III ): ρ < 1; [ IV ∙H∙G] + slow : ρ ≥ 1).…”