To match nature's prowess at using enzymes to make desired motifs in a regioselective fashion, we explore the use of visible light for the selective oxidation of the hydroxyl group to the corresponding ketosaccharide. This highly admirable approach offers several advantages over the enzymatic approach in terms of yields, the scope of substrates. Herein we report the development of a simple visible-light-promoted selective oxidation of unprotected glucosides that allows for inexpensive access to valuable ketosaccharides building blocks. The method is employed on a variety of different natural and artificial glucosides, is operationally simple and scalable, and is applied to access ketosaccharides rapidly and inexpensively.

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....

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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(sp 2 )−C(sp 3 ) linkages on peptides through cross-coupling remains unexplored. In this article, we describe a photoredox-catalyzed C(sp 2 ) 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.

The rapid emergence of resistant bacteria and the scarcity of antibiotic pipeline has been a persistent threat to the global health. To expand the antibiotic pipeline, we have focused our strategy by revitalizing the current antibiotic via novel site-specific derivatization. Aminoglycosides (AGs), once considered effective therapeutics for treating clinical infections, are now seeing limited use due to drug-induced toxicity and AG-resistant bacteria. Challenges in synthesis and modifications of AGs impedes their potential for re-gaining efficacy. Here we discuss a photoredox catalyzed late-stage modification of glucosides including AGs. Our chemistry can selectively install an alkyl group at the 3- position of unprotected glucoside with a broad substrate scope and high yields. Among the products, we characterized a series of compounds that can overcome drug resistance caused by APH (3’) and one of them achieved 30-fold potency compared to kanamycin against sensitive strains. The chemistry we describe here opens a new avenue for discovering new AGs antibiotics that overcome drug resistance and may also serve as the basis for understanding their SARs.

An efficient transition-metal-free tactic for the convergent synthesis of substituted dihydropyrroles and pyrroles by β-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.

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.

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