Trends in the Synthesis of Antimicrobial Derivatives by using the Gewald, Strecker, and Groebke-Blackburn-Bienaymé (GBB) Reactions.

BACKGROUND: Multicomponent reactions are highly useful in synthesizing natural products and bioactive molecules. Out of several MCRs, although utilized widely, some remain neglected in review articles. The Gewald and Groebke-Blackburn-Bienaymé (GBB) reactions are two such reactions. This comprehensive review assimilates applications of Gewald and Groebke-Blackburn- Bienayme reactions in synthesizing novel antimicrobial agents. It presents the antimicrobial properties of the synthesized molecules, providing an overview of their potential druggability. OBJECTIVE: Developing novel antimicrobial agents is the need of the hour. Toward this objective, the scientific community is developing new methods for constructing novel architectures with potential antimicrobial properties. This review will showcase the usefulness of the Gewald, Strecker, and Groebke-Blackburn-Bienaymé (GBB) reactions in synthesizing antimicrobial molecules. METHOD: The articles are searched by using the Sci-finder search tool and summarize the chemistry of their synthesis and antimicrobial evaluation of the molecules Results: This review focuses on synthesizing antimicrobial molecules using the Gewald, Strecker, and Groebke-Blackburn-Bienaymé (GBB) reactions. The antimicrobial activities of the synthesized molecules are also summarized in tables. CONCLUSION: This review will briefly overview the application of the Gewald, Strecker, and Groebke- Blackburn-Bienaymé (GBB) reactions in synthesizing novel antimicrobial molecules. It contains several molecules with promising activity against resistant and non-resistant microbial strains. These promising molecules could be studied further to develop novel antibiotics.

Regioselective Decarboxylative Transformations of Tetrahydro-ß-carboline-1-carboxylic Acid: Reagent Controlled Selectivity toward Alkynylated or Enaminone Products.

A one-pot, regioselective decarboxylative alkynylation of tetrahydro-ß-carboline-1-carboxylic acid under peroxide-free condition is reported. The reaction is highly selective for the 1-position over the 3-position of tetrahydro-ß-carboline. The reaction can afford alkynylated or enaminone products depending on the reagent. The reaction proceeds through sequential decarboxylative iminium ion formation followed by an alkynylation and oxidative rearrangement cascade.

The role of sugar-backbone heterogeneity and chimeras in the simultaneous emergence of RNA and DNA.

Hypotheses of the origins of RNA and DNA are generally centred on the prebiotic synthesis of a pristine system (pre-RNA or RNA), which gives rise to its descendent. However, a lack of specificity in the synthesis of genetic polymers would probably result in chimeric sequences; the roles and fate of such sequences are unknown. Here, we show that chimeras, exemplified by mixed threose nucleic acid (TNA)-RNA and RNA-DNA oligonucleotides, preferentially bind to, and act as templates for, homogeneous TNA, RNA and DNA ligands. The chimeric templates can act as a catalyst that mediates the ligation of oligomers to give homogeneous backbone sequences, and the regeneration of the chimeric templates potentiates a scenario for a possible cross-catalytic cycle with amplification. This process provides a proof-of-principle demonstration of a heterogeneity-to-homogeneity scenario and also gives credence to the idea that DNA could appear concurrently with RNA, instead of being its later descendent.

Phosphorylation, oligomerization and self-assembly in water under potential prebiotic conditions.

Prebiotic phosphorylation of (pre)biological substrates under aqueous conditions is a critical step in the origins of life. Previous investigations have had limited success and/or require unique environments that are incompatible with subsequent generation of the corresponding oligomers or higher-order structures. Here, we demonstrate that diamidophosphate (DAP)-a plausible prebiotic agent produced from trimetaphosphate-efficiently (amido)phosphorylates a wide variety of (pre)biological building blocks (nucleosides/tides, amino acids and lipid precursors) under aqueous (solution/paste) conditions, without the need for a condensing agent. Significantly, higher-order structures (oligonucleotides, peptides and liposomes) are formed under the same phosphorylation reaction conditions. This plausible prebiotic phosphorylation process under similar reaction conditions could enable the systems chemistry of the three classes of (pre)biologically relevant molecules and their oligomers, in a single-pot aqueous environment.

Nitrogenous Derivatives of Phosphorus and the Origins of Life: Plausible Prebiotic Phosphorylating Agents in Water.

Phosphorylation under plausible prebiotic conditions continues to be one of the defining issues for the role of phosphorus in the origins of life processes. In this review, we cover the reactions of alternative forms of phosphate, specifically the nitrogenous versions of phosphate (and other forms of reduced phosphorus species) from a prebiotic, synthetic organic and biochemistry perspective. The ease with which such amidophosphates or phosphoramidate derivatives phosphorylate a wide variety of substrates suggests that alternative forms of phosphate could have played a role in overcoming the "phosphorylation in water problem". We submit that serious consideration should be given to the search for primordial sources of nitrogenous versions of phosphate and other versions of phosphorus.

An efficient combinatorial synthesis of allocolchicine analogues via a triple cascade reaction and their evaluation as inhibitors of insulin aggregation.

A controlled cascade: A divergent, diastereoselective and efficient one-pot synthesis of allocolchicinoids via a cascade Suzuki-Michael addition-Carbocyclization sequence is described. The utility of the compounds as possible inhibitors of insulin aggregation is also presented.

Synthesis of 3H-pyrazolo[3,4-c]isoquinolines and thieno[3,2-c]isoquinolines via cascade imination/intramolecular decarboxylative coupling.

A general approach for the synthesis of 3H-pyrazolo[3,4-c]isoquinolines and thieno[3,2-c]isoquinolines is described involving the implementation of a cascade imination/intramolecular decarboxylative coupling between potassium 2-amino(hetero)benzoates and 2-haloarylaldehydes. The reactions of pyrazole-based substrates require a Pd-Cu bimetallic system for superior yields whereas the thienyl-based substrates afford the products in excellent yields with a Pd-catalyst only.