Current Organic Synthesis - Volume 14, Issue 1, 2017

This review imparts a survey on the synthesis and reactions of ethylidenethiosemicarbazides as well as their biological activities during the period from 2005 to 2015. The synthetic utilities of ethylidenethiosemicarbazides, as building blocks, for the synthesis of various heterocyclic compounds such as azoles, azines, and fused ring systems, have been demonstrated.

Tetraketones have attracted much attention because of their biological activities and molecular structure characteristics. Tetraketones are important precursors extensively used in the synthesis of acridinediones, as laser dyes and for the synthesis of various heterocyclic compounds. Tetraketones show significant lipoxygenase inhibitor activity and strong anti-oxidant potential. Also tetraketones are interesting due to their similar properties to those of 1,4-dihydropyridines, with similar structure to those of biologically important compounds, such as NADH and NADPH. The lipoxygenase inhibiting and antioxidant properties of tetraketones were also studied. Tetraketones as a new class of tyrosinase inhibitors were introduced. These studies lead to the discovery of therapeutically potent agents against clinically important dermatological disorders including hyperpigmentation as well as skin melanoma. Various methods have been reported for the synthesis of compounds belonging to these classes. Each of these methods have their own advantages but also suffer from certain disadvantages such as prolonged reaction time, tedious work-up processes, low yield, high temperature and hazardous reaction conditions. In below the synthesis of tetraketones under different conditions is reported. In this review has been introduced the synthesis and applications of tetraketones in defferent conditions such as acidic, basic, ionic liquid and so on. Also some applications of tetraketones in organic synthesis as well as pharmacology were described.

Benzimidazole and its derivatives are regarded as an important heterocyclic motif that exhibits a wide range of pharmaceutical applications including anticancers, antihypertensives, antivirals, antifungals, anti-HIVs, anti-convulsants, and anti-diabetics. In view of their wide ranging activities, the synthesis of benzimidazoles and its derivatives remain a primary focus for synthetic chemistry communities. Till date numerous reports especially on the synthesis of 2-arylbenzimidazoles have been published but lack of knowledge on the detailed synthetic reports of two important derivatives such as 2-aminobenzimidazoles, and 2-(alkyl/aryl)thio benzimidazoles still persists. However, owing to fast developing benzimidazole containing new drugs numerous reports have appeared on the synthesis of this privileged scaffold. In this review, efforts have been taken to shed light on the latest informations available on the syntheses and applications of different benzimidazole derivatives. We have also tried to summarize the chemistry involved in the synthesis of various derivatives of benzimidazole for medicinal applications.

Nowadays, the stereoselective synthesis of naturally occurring compounds showing biological activity has attracted much attention and stirred up the interest of organic synthetic chemists. Apparently, the multi-step total synthesis of such complex molecules bearing several stereogenic centers demands the development of the efficient and operational strategies for the induction of chirality in a certain step (steps). Among the most practical approaches in the area of stoichiometric asymmetric synthesis, the SAMP/RAMP hydrazone methodology has been found to be a powerful tool in the synthesis of numerous naturally occurring, and bioactive compounds. In this report, we try to highlight the applications of this methodology in asymmetric synthesis. In memory of Professor Abbas Shafiee (1937-2016) who trusted me a while ago on a project led to the production of Codeine Phosphate in Iran.

Background: Pyridazinone derivatives is considered a privileged structure that is currently experiencing a renewed interest in medicinal chemistry. Within this paper we studied the synthesis, structure and stereochemical aspects of some new Z-sinclinal/E-anticlinal acetylhydrazines isomers derived from pyridazin-3(2H)- ones. Methods: The synthesis of the desired pyridazinones with acetylhydrazine skeleton have been done using a classical, straight and efficient method: reaction of the corresponding esters with hydrazine hydrate. The structure of compounds was proven by elemental and spectral analysis: IR, X-ray, NMR. Results: The synthesis is leading to a mixture of Z-sinc (up to 90%) and E-antic (less than 10%) conformers, in a conformational equilibrium. The significant difference in chemical shift between the carbonyl in the Z-sc and in the E-ac (around 5 ppm), could be used as a facile and straight tools to discriminate Z-sc/Eac conformers in the 13C NMR spectra. The temperature dependence 1H NMR studies concerning conformational equilibrium indicating the presence of a single stereoisomer at temperatures higher to 80 °C, the Z-sc isomer. In the case of 4,5- dihydro-3(2H)-pyridazinones bearing a methyl substituent in the alfa position of N1-pyridazine heterocycles, a new class of fused heterocycle with 8,9-dihydropyridazino[1,2,4]triazine structure was obtained and fully characterized. Conclusions: The present study sheds light concerning the synthesis, structure and stereochemical problems of some new Z-sinclinal/E-anticlinal acetylhydrazines isomers derived from pyridazin-3(2H)-ones. Also, a new class of fused heterocycle with 8,9-dihydropyridazino[1,2,4]triazine structure was obtained and fully characterized. A feasible reaction mechanism for cyclisation process is presented. The antimycobacterial activity of compounds was evaluated.

Background: Hybrid systems based on steroids currently are drawing considerable attention in the area of drug development. In our recent work, we reported a Microwave (MW) irradiated Ugi-4 component reaction (Ugi-4CR) in synthesizing a number of steroid-amino acid conjugates based on seco-steroid hydroxyacids (A,B & D ring cleavage) in an expedited way giving very high yield of hybrid products. Considering the importance of steroid based hybrid molecules coupled with advantages of MW energy in organic synthesis, we report here a very high yield synthesis of another class of important hybrid system based on aminosteroids through MWirradiated Ugi-4CR in expedient way. Methods: The systematic investigation on MW energy in Ugi-4CR reaction to synthesize a noval class of hybrid systems based on aminosteroids to make the conjugation process more facile and greener. Results: Unlike classic peptide-coupling strategies, the conjugation of peptide to an aminosteroid could provide a number of opportunities both in structural and synthetic, leading to the possibility of legating two or more peptide chains to a steroid based template in a single process. The application of MW energy expedited the conjugation process. Conclusion: The potential advantages of MW irradiated Ugi-4CR in synthesizing steroid-peptide conjugates based on aminosteroids would undoubtedly find a significant place in commercial synthesis of this class of potential bioactive molecules through green approach. Considering the potential and diverse biological properties associated with steroid hybrid molecules, the present synthesis of steroid-peptide conjugates based on aminosteroids might be of interest in the area of drug development.

Background: Heterocyclic molecules have been synthesized by a green & facile strategy. These molecules contain a 8-membered azocine ring. The structures have been determined by spectral analysis and single crystal X-ray analysis. These compounds have anticancer activity. Method: A mixture of ninhydrin and acetone/ethylmethylketone in acetic acid in molar ratio 1:1 were heated on water bath for 15 minutes. The reaction mixtures were dried on rotary evaporator and crystallized with chloroform- n-hexane (1:1 v/v) to give the colorless crystals of 1 And 2 respectively. Compounds 3 and 4 were synthesized by adding o-phenylenediamine to the completed reaction mixtures of 1 and 2 and each was further heated on water bath for 5 minutes. The dried reaction mixtures were chromatographed over a silica gel column and crystalized as 3 and 4. Results: This strategy resulted novel class of anticancer benzazocines (3 & 4). Conclusion: This method features mild reaction conditions and simple operation. The synthesis completes in two steps; from ninhydrin to 1 & 2 and from 1 & 2 to 3 & 4. The same basic skeleton of 3 & 4 and the same synthesis procedure clearly shows the general applicability of this reaction that is also proved enough by single crystal Xray analysis and the strategy can be applicable for a wide range of other substrates. The obtained compounds are potential anticancer agents.

Background: The pyrrole ring is widely spread and incorporated into the structures of many naturally occurring compounds e.g. heme, chlorophyll, vitamin B12 and the bile pigments. Pyrrolnitrin and pyoluteorin are naturally occurring pyrroles which have antibiotic activity, and the methyl ester of 4-methylpyrrole-2-carboxylic acid is an insect pheromone. Moreover, the highly successful cholesterol lowering drug Lipitor is a poly substituted pyrrole derivative. Methods: Some novel pyrrole derivatives bearing other heterocyclic rings at positions-2 and -3 were synthesized and their antimicrobial activities were studied. Results: A series of novel pyrrolinthione, thiazolidinone, thiazolone, tetrazole, sulphonamides derivatives have been synthesized through a facile strategy and screened for antimicrobial activities, some of the prepared compounds exhibited high antibacterial and antifungal activities compared with the standard drugs. Conclusion: These compounds provided the impetus for most of the early work on the synthesis and reactions of pyrroles and still a very active of research. Many such explorations are anticipated in near future.