Jordy Saya

An intramolecular Prins cyclization of aza-Achmatowicz rearrangement products was developed to construct the versatile 9-azabicyclo[3.3.1]nonane (9-ABN) ring system with a variety of substitution patterns and then applied to the asymmetric total synthesis of six suaveoline and sarpagine alkaloids: macrophylline, suaveoline, norsuaveoline, affinisine, normacusine B and N _a-Me-16-epipericyclivine.

Abstract

An intramolecular aza-Prins cyclization of aza-Achmatowicz rearrangement products was developed in which bismuth tribromide (BiBr₃) plays a dual role as an efficient Lewis acid and source of the bromide nucleophile. This approach enables the facile construction of highly functionalized 9-azabicyclo[3.3.1]nonanes (9-ABNs), which are valuable synthetic building blocks and a powerful platform for the synthesis of a variety of alkaloid natural products and drug molecules. Suitable substrates for the aza-Prins cyclization include 1,1-disubstituted alkenes, 1,2-disubstituted alkenes, alkynes, and allenes, with good to excellent yields observed. Finally, we showcase the application of this new approach to the enantioselective total synthesis of six indole alkaloids: (−)-suaveoline (1), (−)-norsuaveoline (2), (−)-macrophylline (3), (+)-normacusine B (4), (+)-N _a-methyl-16-epipericyclivine (5) and (+)-affinisine (6) in a total of 9–14 steps. This study significantly expands the synthetic utility of the aza-Achmatowicz rearrangement, and the strategy (aza-Achmatowicz/aza-Prins) is expected to be applicable to the total synthesis of other members of the big family of macroline and sarpagine indole alkaloids.

Noncanonical amino acids (ncAAs) bearing functional groups for bioorthogonal labelling are useful tools for the downstream analysis of nascent polypeptides. However, the methionine analogues commonly used are not optimally recognized by the endogenous protein synthesis machinery. TePhe, a tellurophene bearing phenylalanine analogue, is a promising alternative to the methionine analogues as it is readily accepted, and incorporated, during protein synthesis. However, a bioorthogonal reaction to label TePhe was required to enable protein tagging to facilitate analysis. Here we establish that the tellurophene side chain of TePhe is a potent partner in an oxidation-controlled, strain-promoted tellurophene-alkyne cycloaddition (OSTAC) reaction. Mild oxidation of the tellurophene ring with N-chlorosuccinimide produces a Te(IV) species which undergoes rapid (k > 100 M-1s-1) cycloaddition with bicyclo[6.1.0]nonyne (BCN) resulting in a benzo-fused cyclooctane. Selective reaction of TePhe containing proteins can be achieved in complex protein mixtures. OSTAC reactions can be combined with strain-promoted azide alkyne cycloaddition (SPAAC) and copper catalyzed azide alkyne click (CuAAC) reactions. The favorable properties of the OSTAC reaction will likely find wide application beyond its use with TePhe in chemical biology.

Renewable Polymers. In their Communication (e202203353), Mukund P. Sibi, Dean C. Webster, Jayaraman Sivaguru et al. highlight a methodology for the generation of photodegradable and recyclable cross-linked polymers from biomass.

Abstract

The field of peptide derivatization by metal-catalyzed C−H activation has been mostly directed to modify the side chains, but poor attention has been given to the peptide backbone. Here we report a ruthenium-catalyzed C−H activation/annulation process that can chemoselectively modify the peptide backbone producing functionalized isoquinolone scaffolds with high regioselectivity in a rapid and step-economical manner. This strategy is characterized by racemization-free conditions and the production of fluorescent peptides, and peptide conjugates to drugs, natural products and other peptide fragments, providing a chemical approach for the construction of novel peptide-pharmacophore conjugates. Mechanistic studies suggest that amide bonds of peptide backbone act as the bidentate directing group to promote the C−H activation/annulation process. This report provides an unprecedented example of peptide backbone diversification and bioorthogonal ligation exploiting the power of ruthenium-catalyzed C−H activation.

Isocyanide‐based reactions: The development of catalytic enantioselective isocyanide‐based reactions is currently of great interest because the resulting products are valuable in organic synthesis, pharmacological chemistry, and materials science. This review assembles and comprehensively summarizes the recent achievements in this rapidly growing area according to the reaction types. Special attention is paid to the advantages, limitations, possible mechanisms, and synthetic applications of each reaction. In addition, a personal outlook on the opportunities for further exploration is given.

Abstract

The development of catalytic enantioselective isocyanide‐based reactions is currently of great interest because the resulting products are valuable in organic synthesis, pharmacological chemistry, and materials science. This review assembles and comprehensively summarizes the recent achievements in this rapidly growing area according to the reaction types. Special attention is paid to the advantages, limitations, possible mechanisms, and synthetic applications of each reaction. In addition, a personal outlook on the opportunities for further exploration is given at the end.

Advanced Synthesis &Catalysis, EarlyView.

Angewandte Chemie International Edition, EarlyView.

Angewandte Chemie International Edition, EarlyView.

Out-of-plane chiral domain wall spin-structures in ultrathin in-plane magnets

Nature Communications, Published online: 19 May 2017; doi:10.1038/ncomms15302

Chiral domain walls in magnetic films can be electrically controlled, which makes them attractive for applications, but domain walls in ultrathin films are normally non-chiral. Here, the authors observe chiral domain walls in ultrathin Fe/Ni bilayers that are stabilized by the magnetic anisotropy.