Gal Bitan

Building units for N-backbone cyclic peptides. Part 4.1Synthesis of protected Nα-functionalized alkyl aminoacids by reductive alkylation of natural amino acids

A new method for the synthesis of protected nNα-(ω-Y-alkyl) amino acids (Y nis a thio, amino or carboxy group) and related compounds by reductive nalkylation of natural amino acids is reported. These new amino acids nserve as building units for the synthesis of backbone-cyclic peptides. nThey are orthogonally protected at the α-amino position by nbutoxycarbonyl (Boc) or 9-fluorenylmethoxycarbonyl (Fmoc), using ntrimethylsilyl temporary protection, to allow for their incorporation ninto peptides by solid phase peptide synthesis.

Transfer hydrogenation of diarylacetylenes by polymethylhydrosiloxane in the presence of the RhCl3-Aliquat 336 catalyst

Abstract The ion pair [(C 8 H 17 ) 3 NCH 3 ] + [RhCl 4 (H 2 O) 2 ] − , formed from aqueous rhodium chloride and Aliquat® 336, has been shown to catalyze transfer hydrogenation of diarylacetylenes by polymethylhydrosiloxane (PMHS) to give Z - and E -stilbenes as the major and the minor products, respectively. The reduction of diphenylacetylene was found to follow first-order kinetics in the substrate between 0.025 and 2.0 M. Both the steric and the electronic nature of the substrate proved to affect the rate. The electronic effect could be expressed in terms of two separate Hammett plots, one with ϱ = 0.64 for electron-withdrawing substituents and one with ϱ = −1.10 for the alkynes with electron-releasing groups. Application of either a deuterium-labelled organic phase or D 2 O led to mono and dideuterated products. The observed activation energy E a = 11.47 kcal mol −1 suggests that the process is both chemically and diffusion controlled.

New backbone cyclic substance P analogs

Structure-activity relationships of cyclic substance P (SP) analogs were extensively studied in our laboratories utilizing the new concept of backbone cyclization. Employing the C-terminal hexapeptide SP6–11, we examined the influence of chemical changes in peptides containing backbone-to-amino-end cyclization. These changes in the ring have significant influence on activity, and should be carefully designed in order to optimize pharmacological feature.

Synthesis of a bicyclic BPTI mimetic containing 4-thioproline replacing Cys38

The synthesis of a backbone bicyclic nonapeptide that mimics the binding site of bovine pancreatic trypsin inhibitor (BPTI) is described. The BPTI mimetic, which containscis-thioproline replacing Cys38 of the protein, inhibits trypsin with a K i of 76 μM.