Recent developments and comparison of transformation strategies for organic halides to aldehydes and ketones.

Aldehydes and ketones are parts of millions of compounds and are important classes of chemicals which serve as important precursors for the synthesis of library of compounds. For the synthesis of aldehydes and ketones, one impressive approach to date, because of its excellent selectivity, high yield and stability toward over-reduction and over-oxidation, is the oxidation of organic halides (viz. aliphatic and benzyl halides). The current review covers the conventional and eco-friendly transformational approaches, from 2000 to date, toward synthesis of aldehydes and ketones from organic halides, including mechanistic studies, comparison of different transformational strategies and discussion on scope and cons and pros of each transformational approach. The review would be beneficial to get knowledge about recent synthesis techniques, select finest synthetic approach, develop further new transformational methodologies and improve current transformational approaches.

Novel C-2 Symmetric Molecules as α-Glucosidase and α-Amylase Inhibitors: Design, Synthesis, Kinetic Evaluation, Molecular Docking and Pharmacokinetics.

A series of symmetrical salicylaldehyde-bishydrazine azo molecules, 5a-5h, have been synthesized, characterized by 1H-NMR and 13C-NMR, and evaluated for their in vitro α-glucosidase and α-amylase inhibitory activities. All the synthesized compounds efficiently inhibited both enzymes. Compound 5g was the most potent derivative in the series, and powerfully inhibited both α-glucosidase and α-amylase. The IC50 of 5g against α-glucosidase was 0.35917 ± 0.0189 µM (standard acarbose IC50 = 6.109 ± 0.329 µM), and the IC50 value of 5g against α-amylase was 0.4379 ± 0.0423 µM (standard acarbose IC50 = 33.178 ± 2.392 µM). The Lineweaver-Burk plot indicated that compound 5g is a competitive inhibitor of α-glucosidase. The binding interactions of the most active analogues were confirmed through molecular docking studies. Docking studies showed that 5g interacts with the residues Trp690, Asp548, Arg425, and Glu426, which form hydrogen bonds to 5g with distances of 2.05, 2.20, 2.10 and 2.18 Å, respectively. All compounds showed high mutagenic and tumorigenic behaviors, and only 5e showed irritant properties. In addition, all the derivatives showed good antioxidant activities. The pharmacokinetic evaluation also revealed promising results.

Extending the scope of amantadine drug by incorporation of phenolic azo Schiff bases as potent selective inhibitors of carbonic anhydrase II, drug-likeness and binding analysis.

A series of Amantadine-based azo Schiff base dyes 6a-6e have been synthesized and characterized by 1 H NMR and 13 C NMR and evaluated for their in vitro carbonic anhydrase II inhibition activity and antioxidant activity. All of the synthesized showed excellent carbonic inhibition. Compound 6b was found to be the most potent derivative in the series, and the IC50 of 6b was found to be 0.0849 ± 0.00245 µm (standard Acetazolamide IC50  = 0.9975 ± 0.049 µm). The binding interactions of the most active analogs were confirmed through molecular docking studies. Docking studies showed 6b is interacting by making two hydrogen bonds w at His93 and Ser1 residues, respectively. All compounds showed a good drug score and followed Lipinski's rule. In summary, our studies have shown that these amantadine-derived phenolic azo Schiff base derivatives are a new class of carbonic anhydrase II inhibitors.

Synthetic approaches to access acortatarins, shensongines and pollenopyrroside; potent antioxidative spiro-alkaloids with a naturally rare morpholine moiety.

Pyrrole spiroketal alkaloids (PSAs) are a class of novel natural products that have been recently disclosed. Acortatarin A and acortatarin B, two potent antioxidative spiroalkaloids with a naturally rare morpholine moiety, are important members of this class. These spiroalkaloids are isolated from Acorus tatarinowii, Brassica campestris, Capparis spinose, bread crust, Xylaria nigripes and medicine Shensong Yangxin and could inhibit significantly the reactive oxygen species (ROS) production in high-glucose-induced mesangial cells in a time- and dose-dependent manner. Hence, these natural products are promising starting points for the formation of new therapeutics to medicate cardiovascular diseases, cancer, diabetic complications, and other diseases in which ROS are implicated. The impressive structure combined with an interesting pharmacological activity prompted synthetic chemists to construct an asymmetric synthetic strategy that could be used to access structural derivatives in addition to the larger quantities of natural products required for further biological investigations. This review summarizes the current state of the literature regarding with the synthesis of acortatarin A and B and its other family members viz. shensongine A, B and C, and pollenopyrroside A. The present review discusses the pros and cons of synthetic methodologies, which would be beneficial for further developments in the synthetic methodologies. Hopefully, this struggle pushes the reader's mind to consider new perspectives, think differently and forge new connections.

Enzyme inhibitory activities an insight into the structure-Activity relationship of biscoumarin derivatives.

Biscoumarin derivatives, a dimeric form of coumarin, are well known derivatives of coumarin, occurred in the bioactive metabolites of marine and terrestrial organisms. On account of pharmacological and biological applications, biscoumarins have long been the subject of innumerable enzyme inhibition studies. In this review the pros and cons of enzyme inhibition studies of biscoumarins as urease inhibitors, aromatase inhibitors, NPPs, α-glucosidase inhibitors, α-amylase inhibitors, HIV-1 integrase inhibition, steroid sulfatase inhibitors and c-Met inhibitors are discussed in a systematic way. Moreover, the review discusses the structure activity relationship of biscoumarin scaffold with enzyme inhibitory potency which would unleash new avenues for further development. The purpose of the current review is to disclose the value of biscoumarins as potent and efficient enzyme inhibitor. This review provides a guideline to elaborate the diversity of biscoumarin inhibitors by exploring the effects of electronic groups linked with biscoumarin nucleus.

Developments in the synthesis of the antiplatelet and antithrombotic drug (S)-clopidogrel.

S-(+)-Methyl 2-(2-chlorophenyl)-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)acetate, also known as (S)-clopidogrel, is marketed under the trade names Plavix and Iscover. It is a potent thienopyridine-class of antithrombotic and antiplatelet drug (antiaggregant). Among the two available stereoisomers of clopidogrel, for pharmaceutical activities only the S-enantiomer is applicable, as no antithrombotic activity is observed in the R-enantiomer and causes political upheavals and social turmoil in animal experiments. Worldwide sales of Plavix amounted to $6.4 billion yearly, which ranks second. Attributed to the increased demand of (S)-clopidogrel drug, it provoked the synthetic community to devise facile synthetic approaches. This review aims to summarize the synthetic methods of (S)-clopidogrel drug reported in the literature. The present review discusses the pros and cons of each synthetic methodology, which would be beneficial to the scientific community for further developments in the synthetic methodologies for (S)-clopidogrel. In addition, the compilation approach of literature-reported synthetic strategies of (S)-clopidogrel in one platform is advantageous, supportive, and crucial for the synthetic community to elect the best synthetic methodology of (S)-clopidogrel and to create new synthesis ideas.

Synthetic approaches towards the multi target drug spironolactone and its potent analogues/derivatives.

Spironolactone is a well-known multi-target drug and is specifically used for the treatment of high blood pressure and heart failure. It is also used for the treatment of edema, cirrhosis of the liver, malignant, pediatric, nephrosis and primary hyperaldosteronism. Spironolactone in association with thiazide diuretics treats hypertension and in association with furosemide treats bronchopulmonary dyspepsia. The therapeutic mechanism of action of spironolactone involves binding to intracellular mineralocorticoids receptors (MRs) in kidney epithelial cells, thereby inhibiting the binding of aldosterone. Since its first synthesis in 1957 there are several synthetic approaches have been reported throughout the years, Synthetic community has devoted efforts to improve the synthesis of spironolactone and to synthesize its analogues and derivatives. This review aims to provide comprehensive insight for the synthetic endeavors devoted towards the synthesis of a versatile drug spironolactone and its analogues/derivatives.