Bioinspired Total Synthesis of Complex Nucleoside Antibiotics A201A, A201D and A201E.

Herein, bioinspired total syntheses of A201A, A201D, and A201E based on a previously reported biosynthetic pathway are presented. The challenging 1,2-cis-furanoside, a core structure of the A201 family, was obtained by remote 2-quinolinecarbonyl-assisted glycosylation. We accomplished the total synthesis of A201A and A201E based on the critical 1,2-cis-furanoside moiety through late-stage glycosylation without any interference from basic dimethyl adenosine. We also confirmed the absolute configuration of A201E by total synthesis. This modular synthesis strategy enables efficient preparation of A201 family antibiotics, allowing the study of their structure-activity relationships and mode of action. This study satisfies the increasing demand for developing novel antibiotics inspired by the A201 family.

Site-selective C-H alkylation of myo-inositol via organic photoredox catalysis.

Site-selective photoredox reactions with aromatic olefins enable direct alkylation of unprotected myo-inositol at C4. The efficacy of these reactions can be finely tuned by modifying the structures of HAT reagents. These reactions open the possibility of selective C-H alkylations of myo-inositol without the need for multi-step protection-deprotection strategies.

Nonenzymatic Asparagine Motif Synthesis by Photoredox-Catalyzed Carbamoylation of Dehydroalanine.

Post-translational modifications of proteins based on the amino acid residue dehydroalanine (Dha) have been widely adopted in molecular biology to expand their structural and functional capabilities. However, the construction of highly important amide C(sp2)-C(sp3) linkages on peptides through cross-coupling remains unexplored. In this article, we describe a photoredox-catalyzed C(sp2) amidation that enables the mutation of Dha to an asparagine (Asn) motif. This amide installation strategy reported herein will guide us to create more additional derivatives of peptides, which may elucidate the mode of action and address an important area of unmet medical need.

Dithiane-Induced [3+2] Cycloaddition Tactic for the Convergent Synthesis of Dihydropyrrole and Pyrrole Derivatives.

An efficient transition-metal-free tactic for the convergent synthesis of substituted dihydropyrroles and pyrroles by ß-chloro-vinyl dithiane cyclization with a broad range of imines was developed. [3+2] Cyclization and aromatization occur under these reaction conditions providing biologically relevant dihydropyrroles and pyrroles in good yields.