Having developed a general method for the synthesis of 2- iodoisatogens, we wanted to assess the potential of these com- pounds to access new heterocyclic products through elabora- tion of the C-I bond. Our first thoughts were to employ Pd- catalyzed cross-coupling reactions, but the apparent proclivity Scheme 4. Pd-catalyzed cross-coupling
Crotyl alcohol (8.53 ml, 0.1 mol), triethylorthoacetate (46 pi, 0.25 mol) and hexanoic acid (85 pi, 6 mmol) were added to a dried flask which was set up for distillation. The solution was heated in an oil bath with distillation of ethanol. Additional portions of hexanoic acid were added after 3, 3.5 and 4.5 hours. After 6 hours, the solution was cooled and potassium hydroxide (0.1 mol) in water (3 ml) and methanol (75 ml) was added. The reaction mixture was heated at reflux for 1 hour under nitrogen. After cooling to room temperature the solution was washed 3 times with diethyl ether (ether washings discarded) and then acidified with concentrated hydrochloric acid before being extracted with diethyl ether. The organic extracts were dried over anhydrous magnesium sulphate and concentrated on a rotary evaporator to give 3-methylpent-4-enoic acid as a yellow oil (74%) which was used without further purification.1,3 Spectral details matched those published.
The anisole portion was reduced to diene 1.154, which was cleaved via ozonolysis to reveal the C₃ chain of the lycopodine A-ring (1.155). Five more steps, including a Baeyer–Villiger oxidation to turn the enal into a ketone, then furnished synthetic lycopodine (1.4) for the first time. The success of the strategy (B-ring closure onto the D-ring) rendered this synthesis a blueprint for multiple later syntheses that followed similar general strategies. Ayer’s synthesis also started from an anisole derivative 1.156, but added the D-ring last (Scheme 1.26). Unfortunately, while the addition of Grignard reagent 1.158 to iminium ion 1.157 is a conceptually interesting approach, it resulted in the wrong stereochemistry at C-4, which required nine steps to correct. The last ring was finally closed by intramolecular alkylation of mesylate 1.160 to give 1.161 (no yield given). As the ketone was now at C-6 rather than C-5, tedious functional group interconversions were necessary and resulted in a rather lengthy synthesis (26 steps overall).
In light of the observations from literature survey as well as our interest in evolving new, simpler, ecofriendly, convenient methodologies in organic synthesis and absence of reports on the Chapman rearrangement of 3, 6-distigmasteroxypyridazine and 3, 6- dicholesteroxypyridazine led us to undertake the present work in continuation with earlier work. [14, 15, 16, 17, 18, 19,20, 21]
In continuation to our earlier efforts for the synthesis of biologically important compounds employing polymer-supported reagents. The present work described the synthesis of pyrrolo[2,1-b]quinazolinones and related analogues including vasicinone employing polymer-supported reagents for the first time to starting from 2-azidobenzoic acids (48) and various lactams. The synthetic route consists of the coupling of 2- Azidobenzoic acids 48 with different lactams (49) employing N- cyclohexylcarbodiimide, N’-methyl polystyrene (A) to give N-(2- azidobenzoyl)lactams (50), the excess of acid and urea by-products can be simply filtered from azido lactams 49. The intramolecular aza-Wittig reaction has been used extensively for the synthesis of five to seven membered nitrogen heterocyles including vasicinone. Cyclization with triphenyl phospine usually takes place in about 5 h under reflux condition in xylene. This has prompted us to envisage an azidoreductive cyclization process for azidobenzoyl lactams (50-52) to obtain the fused [2,1- b]quinazolinones (53-55) employing polymer-supported triphenyl phosphine (B) under mild conditions in quantitative yield (Scheme-8).
N - [ 6 - ( 7 ,-Trifluoromethylquinolin-4’-yl)hex-5-en-l-yl]phthalimide (VII.38) 4-Bromo-7-trifluoromethylquinoline (2.3 g), A-(hex-5-en-l-yl)phthalimide (2.1 g), palladium acetate (0.020 g), tri-o-tolylphosphine (0.053 g), sodium iodide (0.030 g) and tributylamine (2.0 ml) in dimethylformamide (3.0 ml) were heated at 100° under nitrogen for 17 h. The residue was diluted with water, extracted with ethyl acetate, and the extract washed with dilute hydrochloric acid, saturated sodium bicarbonate solution, water, and then dried (Na 2 SC> 4 ). The solvent was evaporated and the product subjected to column chromatography (alumina; 10-15% ethyl acetate in hexane) and recrystallised from ethanol to give white crystals of the title compound (0.719 g), m.p. 103.5-105° (Found: C, 67.8; H, 4.7; N, 6.5. C 24 H 19 F 3 N 2 O 2 requires C, 67.9; H, 4.5; N, 6.6%). *H n.m.r. 5 1.70, complex, H2,3; 2.44, complex, H4; 3.76; t, J 7 Hz, HI; 6.47, dt, 15,6 16 Hz, 14,5 7 Hz,
Thus, the use o f [3H]diazepam and an appropriate brain membrane preparation provides a simple and efficient in vitro binding assay to assess the affinity of compounds for benzodiazepine receptors. Accordingly this radioligand-receptor-binding assay is used in the present work for the examination of structure-activity relationships of a series of new compounds for this receptor system. The advantage of using this in vitro test system over an in vivo assay ( e.g . anticonvulsant action in rodents) is that it provides a rapid and efficient testing routine without complications arising from differences in drug adsorption and metabolism. Furthermore, only sub-milligram quantities of compounds are required cf. larger amounts needed for whole-animal testing. This is an important consideration when the synthesis of difficult analogues for structure-activity relationship studies is con"templated. Thus this methodology represents an efficient way to direct further synthesis and drug design as w ell as in determining the pharmacologically active part of the compounds under study.
Whilst these reductive conditions have proven successful in many applications including the synthesis of a number of natural products 24–27 there are certain disadvantages that limit the usefulness of the process. The reductive nature of the reaction is a major drawback, the termination of the cyclised radical with a hydrogen atom results in the loss of two functional groups in the transformation of the starting material into the product. Organostannane reagents and their by-products are also particularly toxic and can be difficult to remove from the final product. 28 This causes particular concern for the pharmaceutical industry, where acceptable levels of tin compounds in final products are very low, and it is generally very hard to achieve these low levels during purification. 29 Other disadvantages of these procedures are the need for stoichiometric amounts of organostannane reagent and the relatively high cost of these reagents, issues which are magnified on a large scale making the process unattractive for industry.
Fusion of one heterocyclic system with other biodynamic heterocyclic system results in a molecule with structural diversity and with enhanced pharmacological activity. The fusion of hetero-systems has proved to be an attractive and useful method to design new molecular framework of therapeutically interest. With the objective of exploring new heterocycles, we had synthesized pyrimidobenzothiazoles [1-11], by incorporating two pharmacologically interesting heterocyclic systems; benzothiazole and pyrimidine. Pyrimidobenzothiazole are nitrogen–sulphur containing compounds that have been reported to exhibit a wide spectrum of activities such as GABA receptor binding agents [12,13], antiviral, antitumour, anti-inflammatory, analgesic, anticonvulsant, muscle relaxant, sedative [14-17], etc. During the past few decades, interest has been rapidly growing in the properties and transformations of this sulphur-nitrogenheterocycles [18-21]. In the present investigation we had synthesize derivatives of pyrimidobenzothiazoles from 2-aminobenzothiazole [22-24] and screened for biological activity.
We report here the synthesis of 4 THQs4a-d and 4 isoxazoles7a-d. The THQs were prepared by imino Diels-Alder cycloaddition , between different substituted anilines 1 selected by their ability to donate electrons and facilitate the formation of the imines, aromatic aldehyde 2 (2-furaldehyde), and N-vinylpyrrolidin-2- one 3 as alkene, it last was used as electron-rich alkene because it was an available, stable and cheap reagent, also we used acetonitrile as dissolvent in the presence of 20 mol% of Indium trichloride (III) as catalyst. These coupling reactions were performed under mild conditions (room temperature, 24 h). The synthetic approach adopted to obtain the target compounds is depicted in Scheme 1.
Transition metal-catalysed radical cyclisations have received considerable attention in organic synthesis. The atom transfer cyclisation of (o-haloolefms is currently emerging as a valuable tool for the construction o f carbo- and heterocyclic molecules Recently, the cyclisations of allyl trichloroacetate by copper catalysts have been reported by Nagashima and co-workers.<26,27) This work has shown that y-lactone  can be obtained from allyl trichloroacetate by several cuprous salts in acetonitrile however large amounts of catalysts (10-30%) and high temperatures were required to attain high yields o f the product. Many atom transfer cyclisation approaches use transition-metal complexes to promote carbon-carbon bond formation Transition metals able to function as halogen carriers, with an available n + 1 oxidation state, such as the Cu(I)-Cu(II) couple are normally useful (Scheme 4 1).
In the present synthesis work, we were synthesized viable bio active nitrogen and oxygen atom containing heterocyclic compounds like pyrazole, pyrazolone, coumarin, azo coumarin, and naphthyl coumarin. A metal catalyst free reaction to afford the targeted compounds (1-7) in good yields. All three types of coumarins were synthesized in one step ecofriendly approach under solvent free condition. The beauty of this work easily available primary material, gentle conditions, smooth operation and economical cost. The synthesized compound structures were confirmed by advance spectroscopic techniques and elemental analysis. Besides, compounds also evaluated for their in vitro antimicrobial activity.
This review emphasises on the synthesis of various benzobisthiazole derivatives both linear and angular isomers. According to the position of nitrogen and sulphur atoms in this type of heteroarene, the linear benzobisthiazole moiety has two types of skeleton whereas the angular isomer has three types. Additionally, this review enlightens the role of few benzobisthiazole derivatives in biological field. Eventually a wide variety of other uses of benzobisthiazoles and their polymers are also discussed in brief.
14. Wei-wei M, Ting-ting W, He-ping Z, Zhi-yu W, Jian-ping C, Jian-gang S. Synthesis and evaluation of novel substituted 5-hydroxycoumarin and pyranocoumarin derivatives exhibiting signi.cant antiproliferative activity against breast cancer cell lines. Bioorg Med Chem Lett, 2009; 19: 4570-3.
In search for a novel but potential bioactive drug, compounds 3 and 4 were prepared using simpler chemical methods of synthesis with satisfactory yield. The screening against both gram positive and gram negative bacteria showed that compound 3 is more capable than compound 4 but less than the standards used like ketoconazole and ciprofloxacin.
Small Heterocyclic molecules are very important building blocks in the synthesis of biologically active compounds. These building blocks include nitrogen and oxygen-containing heterocycles which are active against different bacteria as 2- oxazolidinones, 1,3-oxazinan-2-ones, 2-oxazolines, oxazines, morpholine, benzofurans, benzooxazines, Pyrrole derivatives, and many more.
45.57; H, 2.97; N, 17.71; S, 13.52. Found: C, 45.53; H, 2.95; N, 17.50; S, 14.49. General procedure: Synthesis of 8, 10 and 12: To a solution of dimethylpyridine formamidine 2a (0.001 mol) added ω- cyanoacetate (0.001 mol), 5,5 dimethyl cyclohexan – 1,3- dione (0.001 mol), and /or barbutric acid (0.001 mol), in (15 ml) of DMF / 1 ml of glacial acetic acid. The mixture was refluxed for 72h., until the starting materials had disappeared as indicated by TLC. The solvent was poured onto ice/water, the obtained solids crystallized from DMSO.
Although the progress of science is rapid, the treatment of infectious diseases is still a major challenge for scientific world. This is mainly because of the increasing microbial infections and mutations occurring in microbial strains which make them resistant to many of the current therapeutic agents. The main approach to overcome this problem is designing and developing efficient drug molecules. In search of new pharmaceuticals various heterocycles have been investigated for their antimicrobial potential. Recent literature survey showed that azoles especially fluorinated one are dominating in this field. Among the various azoles