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We report an efficient, metal free method for synthesizing tetracyclic spirooxindole derivatives from N-protected isatins and propargyl bromide via Huisgen cycloaddition. This simple and practicle method provides access to spirooxindoles containing five-, six-, or seven-membered rings fused to a triazole ring. [ABSTRACT FROM AUTHOR]

Cyclohepta[b]indoles, prevalent in natural products and pharmaceuticals, are conventionally accessed via metal or Lewis acid‐mediated cycloadditions with prefunctionalized substrates. Our study introduces an innovative sequential catalytic assembly for synthesizing cyclohepta[b]indoles from readily available isatin derivatives. The process involves three catalytic sequences: ring‐closing metathesis, catalytic hydrogenation, and acid‐catalyzed ring expansion. The RCM of 2,2‐dialkene‐3‐oxindoles, formed by butenyl Grignard addition to 3‐allyl‐3‐hydroxy‐2‐oxindoles, yields versatile spirocyclohexene‐3‐oxindole derivatives. These derivatives undergo further transformations, including dibromination, dihydroxylation, epoxidation, Wacker oxidation at the double bond. Hydrogenation of spirocyclohexene‐3‐oxindole yields spirocyclohexane‐3‐oxindoles. Their subsequent acid‐catalyzed ring expansion/aromatization, dependent on the acid catalyst, results in either cyclohepta[b]indoles or cyclohepta[b]indole‐indoline conjugates, adding a unique synthetic dimension. The utility of this methodology is exemplified through the synthesis of an A‐FABP inhibitor, showcasing its potential in pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Nucleic acid-based logic gates have shown great potential in biotechnology, medicine as well as diagnostics. Herein, we have constructed pH-responsive logic devices by utilizing HIV-1 TAR hairpins in combination with a thiazole peptide that exhibits turn-on fluorescence upon interacting with TAR RNA or DNA. Based on this, INHIBIT-AND and YES-INHIBIT-AND logic gates were constructed in parallel. The pH alteration leads to conformational changes of the hairpin structure, enabling the construction of a multi-reset reusable logic system which could be developed for in vitro sensing of the HIV-1 viral RNA. [ABSTRACT FROM AUTHOR]

We present a transition metal‐free direct C‐2 hydroxymethylation of thiazoles using ketones in the presence of KOtBu, leading to the synthesis of thiazole‐2‐diarylcarbinols. The regioselective deprotonation promotes the Csp2−Csp3 bond formation, resulting in the creation of a quaternary centre. The method offers a complementary strategy to traditional cross‐coupling technologies utilizing azole halides and organometallic reagents, thereby expanding the substrate scope. Furthermore, benzothiazoles exhibit compatibility under the mild reaction conditions. Moreover, this method enables the synthesis of thiazolyl diarylcarbinols and bioactive compounds on a multigram scale. [ABSTRACT FROM AUTHOR]

Nucleic acids play crucial roles in transferring cellular information and gene regulations. DNA and RNA molecules have been associated with multiple human diseases and thus offer opportunities for exploring small molecule-based therapeutics. However, developing target-selective molecules possessing well-defined biological activity, has always been challenging. In the current scenario, where the world is continuously experiencing outbreaks of new infectious diseases, it is always important to expand the scope of chemical toolsets to override conventional drug discovery strategies for developing therapeutically relevant drug candidates. The template-directed synthetic approach has emerged as a promising tool for rapid drug discovery. It allows a biological target to template the selection or synthesis of its ligands from a pool of reactive fragments. There are two main template-directed synthetic strategies: thermodynamically controlled dynamic combinatorial chemistry (DCC) and kinetically controlled target-guided in situ click chemistry. Though discovered only two decades ago, these techniques have proven their usefulness for nucleic acid targets, as exemplified by the increasing number of applications with therapeutically important DNA and RNA targets. However, nucleic acid templated synthetic techniques are relatively unexplored in drug discovery compared to protein targets. In this review article, we have presented a detailed discussion of all the reported nucleic acid templated synthetic studies to portray the great potential of this strategy for efficient hit discovery and lead optimisation. This article would assist in expanding the scope and utility of this strategy through a summary of the advancements and emerging applications. Additionally, a brief overview of the catalytic potential of nucleic acids in asymmetric synthesis has been provided to give a valuable vision of the use of nucleic acids to induce enantioselectivity in chiral drug-like candidates. [ABSTRACT FROM AUTHOR]

Herein, we demonstrate for the first time that noncanonical DNA can direct macrocyclization‐like challenging reactions to synthesize gene modulators. The planar G‐quartets present in DNA G‐quadruplexes (G4s) provide a size complementary reaction platform for the bio‐orthogonal macrocyclization of bifunctional azide and alkyne fragments over oligo‐ and polymerization. G4s immobilized on gold‐coated magnetic nanoparticles have been used as target templates to enable easy identification of a selective peptidomimetic macrocycle. Structurally similar macrocycles have been synthesized to understand their functional role in the modulation of gene function. The innate fluorescence of the in situ formed macrocycle has been utilized to monitor its cellular localization using a G4 antibody and its in cell formation from the corresponding azide and alkyne fragments. The successful execution of in situ macrocyclization in vitro and in cells would open up a new dimension for target‐directed therapeutic applications. [ABSTRACT FROM AUTHOR]