Enantiomeric Cyclic Peptides with Different Caco‐2 Permeability Suggest Carrier‐Mediated Transport

Recently, oral absorption of cyclic hexapeptides was improved by N‐methylation of their backbone amides. However, the number and position of N‐methylations or of solvent exposed NHs did not correlate to intestinal permeability, measured in a Caco‐2 model. In this study, we investigate enantiomeric pairs of three polar and two lipophilic peptides to demonstrate the participation of carrier‐mediated transporters. As expected, all the enantiomeric peptides exhibited identical lipophilicity (logD_7.4) and passive transcellular permeability determined by the parallel artificial membrane permeability assay (PAMPA). However, the enantiomeric polar peptides exhibited different Caco‐2 permeability (P_app) in both directions a–b and b–a. The same trend was observed for one of the lipophilic peptide, whereas the second lipophilic enantiomer pair showed identical Caco‐2 permeability (within the errors). These findings provide the first evidence for the involvement of carrier‐mediated transport for peptides, especially for those of polar nature.     

Diastereoselective Cyclobutenol Synthesis: A Heterogeneous Palladium-Catalyzed Oxidative Carbocyclization-Borylation of Enallenols

A highly selective and efficient oxidative carbocyclization/borylation of enallenols catalyzed by palladium immobilized on amino-functionalized siliceous mesocellular foam (Pd-AmP-MCF) was developed for diastereoselective cyclobutenol synthesis. The heterogeneous palladium catalyst can be recovered and recycled without any observed loss of activity or selectivity. The high diastereoselectivity of the reaction is proposed to originate from a directing effect of the enallenol hydroxyl group. Optically pure cyclobutenol synthesis was achieved by the heterogeneous strategy by using chiral enallenol obtained from kinetic resolution.     

Adiabatic passage Hartmann-Hahn cross polarization in NMR under magic angle sample spinning

We have recently demonstrated that polarization transfer using an adiabatic passage through the Hartmann-Hahn condition (APHH-CP) by a variation of the radio-frequency amplitude can substantially improve the transfer efficiency over Hartmann-Hahn cross polarization. Here we show that APHH-CP can be combined with fast magic angle sample spinning (MAS). The heteronuclear dipolar order, established in the course of the transfer, can indeed be created and preserved.     

Derivatives of (2R)-N-Glyoxylbornane-10,2-sultam and Their Use as auxiliaries in the diastereoselective spirocyclization of 2-substituted tryptamines

A crude hydrate 6 and a crystalline hemiacetal 7 of glyoxylamide 4 were prepared from crotonamide 5 (Scheme 2). Particularly hemiacetal 7 , but also 6 and the ‘dimer’ 8 (obtained from 7 ) may serve as homochiral auxiliaries. The structure of 8 was determined by X-ray analysis. By arenesulfonyl halides, tryptimines 12–14 of 4 were diastereoselectively transformed into spirotricycles 15–17 and 19 .     

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