A comprehensive review in current developments of benzothiazole-based molecules in medicinal chemistry.

Thiazole-containing compounds as therapeutic targets for cancer therapy.

Despite the long history of electroorganic synthesis, it did not participate in the mainstream of chemical research for a long time. This is probably due to the lack of equipment and standardized protocols. However, nowadays organic electrochemistry is witnessing a renaissance, and a wide range of interesting electrochemical transformations and methodologies have been developed, not only for academic purposes but also for large scale industrial production. Depending on the source of electricity, electrochemical methods can be inherently green and environmentally benign and can be easily controlled to achieve high levels of selectivity. In addition, the generation and consumption of reactive or unstable intermediates and hazardous reagents can be achieved in a safe way. Limitations of traditional batch-type electrochemical methods such as the restricted electrode surface, the necessity of supporting electrolytes, and the difficulties in scaling up can be alleviated using electrochemical flow cells. Microreactors offer high surface-to-volume ratios and enable precise control over temperature, residence time, flow rate, and pressure. In addition, efficient mixing, enhanced mass and heat transfer, and handling of small volumes lead to simpler scaling-up protocols and minimize safety concerns. Electrolysis under flow conditions reduces the possibility of overoxidation as the reaction mixture is flown continuously out of the reactor in contrast to traditional batch-type electrolysis cells. In this Account, we highlight our contributions in the area of electroorganic synthesis under flow conditions over the past decade. We have designed and manufactured different generations of electrochemical flow cells. The first-generation reactor was effectively used in developing a simple one-step synthesis of diaryliodonium salts and used in proof-of-concept reactions such as the trifluoromethylation of electron-deficient alkenes via Kolbe electrolysis of trifluoroacetic acid in addition to the selective deprotection of the isonicotinyloxycarbonyl (iNoc) group from carbonates and thiocarbonates. The improved second-generation flow cell enabled the development of efficient synthesis of isoindolinones, benzothiazoles, and thiazolopyridines, achieving gram-scale for some of the products easily without changing the reactor design or reoptimizing the reaction parameters. In addition, the same reactor was used in the development of an efficient continuous flow electrochemical synthesis of hypervalent iodine reagents. The generated unstable hypervalent iodine reagents were easily used without isolation in various oxidative transformations in a coupled flow/flow manner and could be easily transformed into bench-stable reagents via quantitative ligand exchange with the appropriate acids. Our second-generation reactor was further improved and commercialized by Vapourtec Ltd. We have demonstrated the power of online analysis in accelerating optimizations and methodology development. Online mass spectrometry enabled fast screening of the charge needed for the cyclization of amides to isoindolinones. The power of online 2D-HPLC combined with a Design of Experiments approach empowered the rapid optimization of stereoselective electrochemical alkoxylations of amino acid derivatives.

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Electroorganic Synthesis under Flow Conditions

Pathogenic microorganisms are causative agents for different types of serious and even lethal infectious diseases. Despite advancements in medication, bacterial and fungal infections continue to be a growing problem in health care. As more and more bacteria become resistant to antibiotics used in therapy and an increasing number of invasive fungal species become resistant to current antifungal medications, there is considerable interest in the development of new compounds with antimicrobial activity. The compounds containing a heterocyclic ring play an important role among organic compounds with biological activity used as drugs in human and veterinary medicine or as insecticides and pesticides in agriculture. Thiadiazoles belong to the classes of nitrogen-sulfur heterocycles with extensive application as structural units of biologically active molecules and as useful intermediates in medicinal chemistry. The potency of the thiadiazole nucleus is demonstrated by the drugs currently used. 1,3,4-Thiadiazoles and some of their derivatives are extensively studied because of their broad spectrum of pharmacological activities. The aim of this review was to highlight the main antimicrobial properties exhibited by derivatives possessing 2-amino-1,3,4-thiadiazole moiety. Many of the reported 2-amino-1,3,4-thiadiazole derivatives can be considered as lead compounds for drug synthesis, and several of them have demonstrated higher antimicrobial activity in comparison to standard drugs. Furthermore, taking into account the reactivity of the amine group in the derivatization process, 2-amino-1,3,4-thiadiazole moiety may be a good scaffold for future pharmacologically active 1,3,4-thiadiazole derivatives.

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2-Amino-1,3,4-thiadiazole as a potential scaffold for promising antimicrobial agents.

A catalyst- and supporting electrolyte-free method for
electrochemical dehydrogenative C–S bond formation in continuous
flow has been developed. A broad range of N‑ arylthioamides have
been converted to the corresponding benzothiazoles in good to
excellent yields and with high current efficiencies. This transformation
is achieved using only electricity and laboratory grade solvent,
avoiding degassing or the use of inert atmosphere. This work
highlights three advantages of electrochemistry in flow, which is (i) a
supporting electrolyte-free reaction, (ii) an easy scale‑ up of the
reaction without the need for a larger reactor and, (iii) the important
and effective impact of having a good mixing of the reaction mixture,
which can be achieved effectively with the use of flow systems. This
clearly improves the reported methods for the synthesis of
benzothiazoles.

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Catalyst- and Supporting Electrolyte-Free Electrosynthesis of Benzothiazoles and Thiazolopyridines in Continuous Flow

Heterocycles bearing nitrogen, sulphur and thiazole moieties constitute the core structure of a number of biologically interesting compounds. Benzothiazole, a group of xenobiotic compounds containing a benzene ring fused with a thiazole ring, are used worldwide for a variety of therapeutic applications. Benzothiazole and their heterocyclic derivatives represent an important class of compounds possessing a wide spectrum of biological activities. The myriad spectrum of medicinal properties associated with benzothiazole related drugs has encouraged the medicinal chemists to synthesize a large number of novel therapeutic agents. Several analogues containing benzothiazole ring system exhibit significant antitumour, antimicrobial, antidiabetic, anti-inflammatory, anticonvulsant, antiviral, antioxidant, antitubercular, antimalarial, antiasthmatic, anthelmintic, photosensitizing, diuretic, analgesic and other activities. This article is an attempt to present the research work reported in recent scientific literat...

https://www.tandfonline.com/doi/pdf/10.3109/14756366.2012.720572

Alka Sinhmar

Papers

Medicinal significance of benzothiazole scaffold: an insight view