Total synthesis of chrysamide B

We report an efficient synthesis of the dimeric trans-epoxyamide chrysamide B, recently isolated from the deep-sea-derived fungus Penicillium chrysogenum SCSIO41001. Our synthetic strategy exploits a convergent approach using solid-phase peptide synthesis for the piperazine core and a Sharpless-Katsuki epoxidation to prepare the chiral epoxyacid. The double amidation final step provides chrysamide B that was thoroughly characterized with all spectra identical to those of the natural sample. The approach was devised to facilitate the preparation of a library of analogs of chrysamide B

Total synthesis of pseudacyclins A-E by an on-resin head-to-side chain concomitant cyclization-cleavage reaction

Taking advantage of the nucleophile-sensitive ester link of oxime resin, a novel synthetic strategy was applied to the first synthesis of a type of cyclic peptides known as pseudacyclins A–E. The endocyclic ornithine side-chain part was incorporated by an on-resin acid-catalyzed concomitant cyclization-cleavage reaction after a selective deprotection of orthogonally protected ornithine. The synthetic methodology gives high macrocyclization yields and low oligomerization side-products. The combination used of solid-phase/solution-phase strategy was efficient to prepare pseudacyclins and could prove useful to prepare other natural cycle-tail peptides

A novel route towards cycle-tail peptides using oxime resin : teaching an old dog a new trick

Two anabaenopeptins, Schizopeptin 791 and anabaenopeptin NZ825, have similar structural features and have been synthesized via a novel acid-catalyzed head-to-side-chain concomitant cyclization/cleavage reaction on oxime resin. The methodology gave rapid access to the anabaenopeptin scaffold by taking advantage of a combined solid-phase/solution-phase synthetic strategy. Also, as side-products of the synthesis, large C2-symmetric 38-member cyclic peptides ring bearing two endocyclic lysine side-chains were isolated, constituting a novel cyclic peptide scaffold

Revisiting the Juliá–Colonna enantioselective epoxidation : supramolecular catalysis in water

We describe an efficient epoxidation process leading to chiral epoxyketones using the reusable homo-oligopeptide poly-L-leucine (PLL) in pure water, without any organic co-solvent. A range of substituted epoxyketones can be accessed with good conversions and high enantioselectivities. Based on the experimental results and computational studies, we propose a mechanism that demonstrates the importance of both the α-helical structure and the presence of a hydrophobic groove of the homo-oligopeptide catalyst for reactivity and selectivit

Chemical composition of the unexplored volatile fraction of betula glandulosa, a prevalent shrub in Nunavik, Québec

The volatile fraction of the leaves of Betula glandulosa Michx. has been investigated for its secondary metabolite composition by GC/MS and GC/FID. The rapid expansion of this shrub species in subarctic landscapes, like the ones found in Nunavik (Northern Québec, Canada), highly impacts ecosystem dynamics. Yet, despite its abundance, few phytochemical investigations have yet been conducted on this species. In this study, we present the first phytochemical investigation of the volatile metabolites of B. glandulosa leaves. Although no essential oil was isolated, volatile compounds were extracted from the hydrosol by steam distillation. The main metabolites observed were linalool (14.6–19.0 %), C6 oxylipins (known as green leaf volatiles, GLV; total of 18.2–40.2 %), eugenol (1.6–8.6 %) and α-terpineol (3.3–4.8 %). Dwarf birch is an important food source for insects and herbivores, so knowledge of its metabolite composition could help understand parts of its functional role in subarctic ecosystems. The composition of the volatile fraction could serve as marker for differentiating B. glandulosa from other dwarf birch species like Betula nana L

Total synthesis of Crotogossamide using an on-resin concomitant cyclization/cleavage reaction

Crotogossamide, a cyclic peptide isolated from the latex of Croton gossypifolius, has been synthesized by a rapid and efficient Boc solid-phase peptide synthesis. The strategy takes advantage of the oxime resin nucleophile susceptibility and comprises the synthesis of a linear precursor followed by on-resin head-to-tail concomitant cyclization/cleavage. In addition, we report the first antimicrobial and antibiofilm investigations on Crotogossamide

Crown ether helical peptides are preferentially inserted in lipid bilayers as a transmembrane ion channels

Oriented circular dichroism was used to study the alignment crown ether-modified peptides. The influence of different N- and C-functionalities was assessed using at variable peptide:lipid ratios from 1:20 to 1:200. Neither the functionalities nor the concentration had any major effect on the orientation. The alignment of the 21-mer peptides was also examined with lipid membranes of different bilayer thickness. The use of synchrotron radiation as light source allowed the study of peptide:lipid molar ratios from 1:20 to 1:1000. For all conditions studied, the peptides were found to be predominantly incorporated as a transmembrane helix into the membrane, especially at low peptide concentration, but started to aggregate on the membrane surface at higher peptide:lipid ratios. The structural information on the preferred trans-bilayer alignment of the crown ether functional groups explains their ion conductivity and is useful for the further development of membrane-active nanochemotherapeutics

Membrane assembly and ion transport ability of a fluorinated nanopore

A novel 21-residue peptide incorporating six fluorinated amino acids was prepared. It was designed to fold into an amphiphilic alpha helical structure of nanoscale length with one hydrophobic face and one fluorinated face. The formation of a fluorous interface serves as the main vector for the formation of a superstructure in a bilayer membrane. Fluorescence assays showed this ion channel's ability to facilitate the translocation of alkali metal ions through a phospholipid membrane, with selectivity for sodium ions. Computational studies showed that a tetramer structure is the most probable and stable supramolecular assembly for the active ion channel structure. The results illustrate the possibility of exploiting multiple Fd-:M+ interactions for ion transport and using fluorous interfaces to create functional nanostructures