Targeting telomerase reverse transcriptase with the covalent inhibitor NU-1 confers immunogenic radiation sensitization.

Beyond synthesizing telomere repeats, the telomerase reverse transcriptase (TERT) also serves multiple other roles supporting cancer growth. Blocking telomerase to drive telomere erosion appears impractical, but TERT's non-canonical activities have yet to be fully explored as cancer targets. Here, we used an irreversible TERT inhibitor, NU-1, to examine impacts on resistance to conventional cancer therapies.

Correction: Reductive annulations of arylidene malonates with unsaturated electrophiles using photoredox/Lewis acid cooperative catalysis.

[This corrects the article DOI: 10.1039/C9SC00302A.].

Combined Photoredox and Carbene Catalysis for the Synthesis of Ketones from Carboxylic Acids.

As a key element in the construction of complex organic scaffolds, the formation of C-C bonds remains a challenge in the field of synthetic organic chemistry. Recent advancements in single-electron chemistry have enabled new methods for the formation of various C-C bonds. Disclosed herein is the development of a novel single-electron reduction of acyl azoliums for the formation of ketones from carboxylic acids.

Targeted Covalent Inhibition of Telomerase.

Telomerase is a ribonuceloprotein complex responsible for maintaining telomeres and protecting chromosomal integrity. The human telomerase reverse transcriptase (hTERT) is expressed in ∼90% of cancer cells where it confers the capacity for limitless proliferation. Along with its established role in telomere lengthening, telomerase also serves noncanonical extra-telomeric roles in oncogenic signaling, resistance to apoptosis, and enhanced DNA damage response.

Reductive Arylation of Arylidene Malonates Using Photoredox Catalysis.

A strategy with arylidene malonates provides access to -umpolung single-electron species. Reported here is the utilization of these operators in intermolecular radical-radical arylations, while avoiding conjugate addition/dimerization reactivity that is commonly encountered in enone-based photoredox chemistry. This reactivity relies on tertiary amines that serve to both activate the arylidene malonate for single-electron reduction by a proton-coupled electron transfer mechanism as well as serve as a terminal reductant.

Combined Photoredox/Enzymatic C-H Benzylic Hydroxylations.

Chemical transformations that install heteroatoms into C-H bonds are of significant interest because they streamline the construction of value-added small molecules. Direct C-H oxyfunctionalization, or the one step conversion of a C-H bond to a C-O bond, could be a highly enabling transformation due to the prevalence of the resulting enantioenriched alcohols in pharmaceuticals and natural products,. Here we report a single-flask photoredox/enzymatic process for direct C-H hydroxylation that proceeds with broad reactivity, chemoselectivity and enantioselectivity.

Reductive annulations of arylidene malonates with unsaturated electrophiles using photoredox/Lewis acid cooperative catalysis.

A cooperative Lewis acid/photocatalytic reduction of salicylaldehyde-derived arylidene malonates provides access to a versatile, stabilized radical anion enolate. Using these unusual umpolung operators, we have developed a novel route to access densely functionalized carbo- and heterocycles through a radical annulation addition pathway.

An Enantioselective Cross-Dehydrogenative Coupling Catalysis Approach to Substituted Tetrahydropyrans.

An enantioselective cross-dehydrogenative coupling (CDC) reaction to access tetrahydropyrans has been developed. This process combines in situ Lewis acid activation of a nucleophile in concert with the oxidative formation of a transient oxocarbenium electrophile, leading to a productive and highly enantioselective CDC. These advances represent one of the first successful applications of CDC for the enantioselective couplings of unfunctionalized ethers.

A Biocatalytic Route to Highly Enantioenriched β-Hydroxydioxinones.

A novel biocatalytic system to access a wide variety of β-hydroxydioxinones from β-ketodioxinones employing commercial engineered ketoreductases has been developed. This practical system provides a remarkably straightforward solution to limitations in accessing certain chemical scaffolds common in β-hydroxydioxinones that are of great interest due to their diversification capabilities. A few highlights of this system are that it is high yielding, highly enantioselective, and chromatography-free.