Three 1-aminoindanes, four anilines and BnOH or t-BuOH were reacted with chlorosulfonyl isocyanate to give sulfamoyl carbamates. Pd-C catalysed hydrogenolysis reactions of carbamates or deprotection of the Boc group of the carbamates with CF3 CO2 H afforded seven novel sulfamides. Human carbonic anhydrase (hCA) isoenzymes I and II (hCA I and hCA II) were purified from fresh human blood erythrocytes with one-step affinity chromatography on Sepharose 4B-tyrosine-sulfanilamide. The inhibitory properties of the novel sulfamides on both isoenzymes were determined using the esterase activity with 4-nitrophenyl acetate (NPA) as substrate. The tested novel sulfamides derived from 1-aminoindanes and anilines effectively inhibited hCA I and II competitively in the nanomolar range. Among these compounds, the novel sulfamide derivative 17 showed the most potent inhibitory effect against hCA I (Ki : 153.88 nM), while sulfamide derivative 26 showed the highest inhibitory potential against hCA II (Ki : 117.80 nM).
A series of diaryl ethers were synthesized and their human (h) carbonic anhydrase (CA) isoenzymes hCA I and II, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) inhibitory actions were investigated. The new compounds were synthesized from the corresponding phenols and bromobenzenes via the Ullmann reaction, by using dipicolinic acid as a copper (I) complexing ligand. hCA I and II were inhibited with K i s in the low nanomolar range of 102.01-127.13 nM against hCA I, and of 73.71-113.40 nM against hCA II, whereas the inhibition constants against AChE were of 15.35-18.34 nM and against BChE in the range of 9.07-22.90 nM. The CA inhibition mechanism with these ethers is unknown, but may be similar to that of aryl methyl ethers investigated earlier by computational approaches.
The polyhydroxy cyclohexanes have been an interest to those concerned with carbohydrates 1 . The first known cyclohexanepentol was a dextrorotatory cyclitol obtained from the acorns of Quercus species (oaks) 2 , hence the name (+)-proto-quercitol. "Quercitol" has been used as a generic term for cyclohexanepentols. Ten diastereoisomers are predicted for the quercitols. All 10 are known and only the (+)-proto, 2 (-)-proto, 3 and (-)-vibo 4 stereoisomers have been found in nature. Methods which have been used for quercitol synthesis include reduction (hydrogenation) of inososes, inosos oximes, or deoxyinososes; hydrogenation of bromoquercitols; reduction of anhydroinositols; and transformation of conduritols. 5 Meanwhile, synthesis of talo-quercitol and vibo-quercitol was described by McCasland 6 and Nakajima 7 starting from haloinositols and conduritol-E, respectively. In all previously reported syntheses, starting materials have been natural products or compounds which required many steps to synthesize. Recently we described a simple route leading to the synthesis of quercitols where we applied for the first time a singlet oxygen ene reaction combined with the singlet oxygen [2 + 4] addition 8 successively to the synthesis of proto-quercitol 9,10 and gala-quercitol. 10 Here with we describe a short and efficient synthesis of (()-talo-quercitol and (()-viboquercitol starting from commercial 1,3-cyclohexadiene where we used again ene reaction of singlet oxygen. 11
Results and Discussion1,4-Cyclohexadiene 1 was used as the starting material for the synthesis of talo-quercitol. OsO 4 -catalyzed NMO oxidation 12 of 1 afforded diol 2. The resulting cis-diol 2 was protected by ketal formation with 1,2-dimethoxypropane. Tetraphenylporphyrin-sensitized photooxygenation of ketal 3 in methylene chloride at room temperature gave the hydroperoxide 4 in high yield, via ene reaction of singlet oxygen, as the sole product (Scheme 1). The peroxide linkage is highly susceptible to reductive cleavage by a variety of reductants. 13 Selective reduction of peroxide linkage was performed with thiourea under very mild conditions to give the alcohol 5a. Since the only oxygen-oxygen bond breaks in this reaction, it preserves the configuration at the peroxidebonded carbon atom. For further structural proof, 5a was converted to the corresponding acetate 5b which has been fully characterized on the basis of the spectroscopic data.Proton and carbon NMR studies of 5b indicated the formation of an unsymmetrical compound as expected. The proton adjacent to the acetoxy group appears as a multiplet at 5.28 ppm, the alkoxy protons at 4.32 ppm as a multiplet, and the methylene protons appear as an AB system at 2.31 and 1.65 ppm. An 11-line 13 C NMR spectrum is also in agreement with the proposed constitution. However, on the basis of NMR data alone we were not able to assign the correct configuration of the acetoxy group. The configuration of the acetoxyl group was confirmed by observation of NOE effects. Irradiation at the resonance signals of alko...
In this work, nine new bromophenol derivatives were designed and synthesized. The alkylation reactions of (2-bromo-4,5-dimethoxyphenyl)methanol (7) with substituted benzenes 8–12 produced new diaryl methanes 13–17. Targeted bromophenol derivatives 18–21 were synthesized via the O-Me demethylation of diaryl methanes with BBr3. Moreover, the synthesized bromophenol compounds were tested with some metabolic enzymes such as acetylcholinesterase (AChE), carbonic anhydrase I (CA I), and II (CA II) isoenzymes. The novel synthesized bromophenol compounds showed Ki values that ranged from 2.53 ± 0.25 to 25.67 ± 4.58 nM against hCA I, from 1.63 ± 0.11 to 15.05 ± 1.07 nM against hCA II, and from 6.54 ± 1.03 to 24.86 ± 5.30 nM against AChE. The studied compounds in this work exhibited effective hCA isoenzyme and AChE enzyme inhibition effects. The results show that they can be used for the treatment of glaucoma, epilepsy, Parkinson’s as well as Alzheimer’s disease (AD) after some imperative pharmacological studies that would reveal their drug potential.
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