Ahmet Maraş

Synthesis and Carbonic Anhydrase Inhibitory Effects of Novel Sulfamides Derived from 1-Aminoindanes and Anilines

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 CF3CO2H 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).

Synthesis of diaryl ethers with acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase inhibitory actions

Abstract 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 Kis 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.

A Novel Synthesis of Conduritol-C and Conduritol-E via p-Benzoquinone

Abstract A new and stereospecific synthesis for Conduritol-C 8 and Conduritol-E 13a has been developed starting from p-benzoquinone 1. 1,4-oxygen functionalities were introduced in both synthesis by the reduction of dibromo p-benzoquinone 2 with NaBH4. 2,3-oxygen functionalities were introduced by KMnO4 oxidation of 4 for Conduritol C 8. Oxidation of 3 with m-chloroperbenzoic acid gave 9. Acid-catalyzed ring opening reaction of 9 gave 10a which leads to Conduritol-E.

A short synthesis of 4-amino-3-hydroxybutyric acid (GABOB) via allyl cyanide

Abstract4-Amino-3-hydroxybutyric acid was synthesized from allyl cyanide in four steps in an overall yield of 38%. Ultrasonically promoted epoxidation of allyl cyanide with m-chloroperoxybenzoic acid giving oxiranylacetonitrile was used as a key step.

Alternative, high-yield synthesis of (E)-4-oxonon-2-enoic acid from 2-methoxyfuran

Abstract Alkylation of 2‐methoxyfuran, followed by in situ TPP‐sensitized photooxygenation of 2‐methoxy‐5‐pentylfuran in the presence of Me2S, gave methyl (Z)‐4‐oxonon‐2‐enoate. Hydrolysis of methyl (Z)‐4‐oxonon‐2‐enoate afforded (E)‐4‐oxonon‐2‐enoic acid in three steps and in 79% overall yield.

One-pot synthesis from 1,4-cyclohexadiene of (±)-1,4/2,5-cyclohexanetetrol, a naturally occurring cyclitol derivative

Abstract SeO 2 -catalyzed direct hydroxylation of 1,4-cyclohexadiene with two molar equivalents of 30% H 2 O 2 afforded (±)-1,4/2,5-cyclohexanetetrol, a naturally occurring cyclitol derivative, as the sole product in a good yield (88%).

Synthesis of Two Alnustone-Like Natural Diarylheptanoids via 4 + 3 Strategy

Abstract The first total synthesis of (4E,6E)-1,7-bis(3,4-dihydroxyphenyl)-hepta-4,6-dien-3-one and an alternative synthesis of (4E,6E)-1,7-bis(4-hydroxyphenyl)-hepta-4,6-dien-3-one, two natural diarylheptanoids, mainly based on Claisen–Schmidt condensation were described. The crucial steps of the syntheses were the condensation of OH-protected 4-aryl-2-butanones with OH-protected 3-aryl-acrylaldehydes by the in situ enamination and then deprotection of OH groups to give the corresponding natural diarylheptanoids.

Diarylmethanon, bromophenol and diarylmethane compounds: Discovery of potent aldose reductase, α-amylase and α-glycosidase inhibitors as new therapeutic approach in diabetes and functional hyperglycemia

Diabetes mellitus (DM) is a chronic metabolic disease in which there are high blood sugar levels over a prolonged period. Aldose reductase (AR) belongs to aldo-keto reductase superfamily and plays a key role in the polyol pathway. α-Glycosidase and α-amylase are important enzymes in glucose metabolism. In this study, AR was purified from purified from cow liver. The enzyme was obtained with 139.17 purification fold and with a specific activity of 1.67 EU/mg protein. Then, it is observed the inhibition effect of diarylmethanons (1a-d), bromophenols (2a-d and 4a-d) and diarylmethanes (3a-d) on aldose reductase, α-glycosidase and α-amylase enzymes. In these series, compound 2a showed lowest inhibitory activity against AR with a Ki value of 1.09 ± 0.29 μM while compound 2d showed highest inhibitory activity against AR with a Ki value of 0.092 ± 0.015 μM. Additionally, α-glycosidase and α-amylase enzymes were easily inhibited by these compounds. All compounds were tested for their inhibition effects against of α-glycosidase enzyme and demonstrated efficient inhibition profiles with Ki values in the range of 14.44 ± 0.88-43.53 ± 9.06 nM, and IC50 values in the range of 11.72-46.11 nM. Also, inhibition of the α-amylase enzyme, which determined an effective inhibition profile with IC50 values, is in the range of 3.84-29.61 nM.