Current Organic Chemistry - Volume 25, Issue 21, 2021

Alzheimer’s is a neurodegenerative pathology. The first therapeutic strategy for the treatment of AD was mainly acetylcholinesterase inhibitors (AChEIs) such as Tacrine; a linear tricyclic compound that occupies an important place in the treatment of this disease with its properties pharmacophore. In this regard, the development of tacrine-analogs more efficient and safe with new measures and investigations has drawn immense attention. Various structural modifications of Tacrine have been carried out on different parts. Mainly some modification in the ring structure of tacrine or by connecting the amino group with different hybrids based on natural or synthetic compounds and drugs already in existence. These tacrine congeners have considerable potential for the development of new drugs for the treatment of Alzheimer's disease. Therefore, this review presents an overview of the most important structural modifications in tacrine rings based on the current trends reported in recent decades towards the use of natural products and synthetic analogs as a source of new anti-Alzheimer drugs.

The present review focuses on the synthesis of two heteroatoms containing sixmembered heterocyclic compounds, i.e., pyrimidine. In this review, a number of pyrimidine derivatives have been illustrated, which show the exceptional ability towards clinical practices. Pyrimidine derivatives show antimicrobial, antibacterial, antifungal, antiallergic, antiinflammatory, anticancer, and anticonvulsant activities. Therefore, researchers are encouraged to synthesize novel, potent, safe, and selective pyrimidine derivatives that are effective against the mutant strains, and the development of synthetic protocols is a high priority in medicinal chemistry research. Many methodologies have been developed for the preparation of pyrimidine derivatives. In this review article, the synthetic strategies of pyrimidine derivatives are classified into metal-catalyzed synthesis, ionic-liquid assisted synthesis, microwave-assisted synthesis, and solid-phase synthesis.

The fluorinated compounds have significance in medicinal chemistry and pharmaceutical research. The introduction of fluorine atom in the heterocyclic compounds increases biological activity by favourable physiochemical interactions. The combination of heterocycles with fluorine substituents has a wide range of applications in the study of various pharmacological research. The compounds not only exhibit biological activity but have also shown unique physical and chemical characteristics features that open the new avenues for multidisciplinary research. Fluorine atom tolerance to maximal functional groups, simplicity in operation, replacing hydrogen with fluorine of bioactive molecules are more efficient for the synthesis of fluorinated compounds at the commercial level. The fluorine substitution also increases the binding affinity to the targeted protein. Furthermore, the incorporation of fluorine on the drug molecules helps in enhancing the polarity, increasing the rate of drug metabolism and improving metabolic stability. The pharmacokinetic study plays an important role in clinical research. In 1996, researcher Whitford found that the pharmacokinetics of fluorine is affected by pH and quantity in the bone study. The pH of organofluoride influences fluoride absorption, distribution, and excretion. It also increases the stability when bound to carbon atom, resulting in increased bioactivity. This is the primary reason that fluoride is a key component of around 25% of currently available active drugs for various diseases, including cancer, diabetes, HIV etc. Not only the pharmacokinetic properties but also the physical properties of the drug can be enhanced or altered by selective insertion at the key place of the fluorine atom in the drug candidate. In this report, we have studied and referred to the interesting research articles reported since 2000 for the synthesis of low fluorine substituted organic compounds for medicinal research and pharmacokinetic use, example neurological diseases, cancer, and tuberculosis research.

Cascade reactions catalyzed by immobilized multi enzymatic systems are emerging as a tool to address the increasing need for green and sustainable chemistry. In this regard, the carrier-free immobilization strategy of combined cross-linked enzymes aggregates (combi- CLEAs) is of great interest. In a combi-CLEAs two or more enzymes are co-immobilized into a single unit where they are accommodated in close proximity in order to minimize the intermediates diffusion in the reaction medium, at the same time allowing the access of substrates and coenzymes to the active sites. The use of CLEAs provides a simple and low cost methodology that enhances operational and storage enzyme stability and facilitates biocatalyst recovery and recycle. Some significant applications of cascade reactions catalyzed by combi- CLEAs are reported in this mini-review. These examples have been applied on a multigram scale and have furnished practical steps towards the implementation of enzymes on an industrial scale.

One new eudesmane sesquiterpene 1 and one new chromolaevane sesquiterpene 2, along with 19 known compounds, have been isolated from the invasive plant Solidago canadensis. Their structures were established by spectroscopic means, including 1D/2D-NMR and HR-ESIMS analyses. Compounds 10 and 12, in combination with fluconazole, showed significant activity in an in vitro synergistic antifungal assay against Candida albicans, with FIC values of <0.15625 and <0.28125, respectively. Meanwhile, the allelopathic effects of these sesquiterpenes on Arabidopsis seed germination were also tested. Compounds 5, 7, 17 and 18 retarded the seed germination of Arabidopsis with IC50 values ranging from 9.1 to 41 μg/mL, while other compounds showed no obvious inhibitory effects.