Nurullah Saracoglu

α-Carbonic anhydrases are sulfatases with cyclic diol monosulfate esters

Carbonic anhydrases (CA) catalyze activated ester hydrolysis in addition to the hydration of CO2 to bicarbonate. They also show phosphatase activity with 4-nitrophenyl phosphate as substrate but not sulfatase with the corresponding sulfate. Here we prove that the enzyme is catalyzing the synthesis of cyclic diols from sulfate esters. 5-, 6- and 8-membered ring cyclic sulfates incorporating a neighboring secondary alcohol moiety were treated with CA II and yielded the corresponding cyclic diols. Inhibitory properties of obtained cyclic and original sulfate esters were then investigated on human carbonic anhydrase I (hCA I), hCA II, hCA IV and hCA VI (h = human isoform). KI-s of these compounds ranged between 32.7–423 μM against hCA I, 2.13–32.4 μM against hCA II, 13.7–234 μM against hCA IV and 76–278 μM against CA VI, respectively. The sulfatase activity of CA with such esters is amazing considering the fact that 4-nitrophenyl-sulfate is not a substrate of these enzymes.

Functionalization of Indole and Pyrrole Cores via Michael-Type Additions

The Michael reaction has been the subject of numerous reviews. Furthermore, the first review on anti-Michael addition has been published. The present review focuses only on the functionalization of indoles and the pyrroles via Michael additions because of the potential biological activity exhibited by these compounds.

Bile acid derivatives of 5-amino-1,3,4-thiadiazole-2-sulfonamide as new carbonic anhydrase inhibitors: synthesis and investigation of inhibition effects.

Bile acid amides (cholan-24-amides) of 5-substituted 1,3,4-thiadiazole-2-sulfonamide have been prepared from lithocholic, deoxycholic, cholic and dehydrocholic acids. Besides, the alcohol functional groups on the cholane ring systems were protected with acetyl group. Amides of the protected cholanes of lithocholic and cholic acids were also synthesized. Later, inhibition effects of these compounds on human carbonic anhydrase isozymes (HCA-I and II) have been investigated in vitro. For the most active compounds, inhibition constants ranged from 66 to 190nM for HCA-II with I(50) (molarity of inhibitor producing a 50% inhibition of CA activity). In addition, in vivo studies were performed for the synthesized compounds in Sprague-Dawley rats. The compounds (11 and 18) showed especially significant inhibition efficacy (p<0.001).

A New Method for the Synthesis of Stipitatic Acid Isomers: Photooxygenation of Ethyl 6H-Cyclohepta[d][1,3]dioxole-6-carboxylate

Photooxygenation of the cycloheptatriene derivative 9 gave the bicyclic endoperoxide 14. Cleavage of the peroxide linkage in 14 with thiourea resulted in the formation of 16. Treatment of the endoperoxide 14 with a catalytic amount of triethylamine provided a new isomer of stipitatic acid 11, and 16. Pyrolysis or the CoTPP (TPP = tetraphenylporphyrin) catalyzed reaction of 14 resulted in the formation of iso-stipitatic acid 10, and 18.

BROMINATION OF BENZHOMOBARRELENE DERIVATIVES : 10. HIGH TEMPERATURE BROMINATION

Abstract The electrophilic addition of bromine to benzhomobarrelene derivatives 18a and 18b in CCl4 at low temperatures (O °C) followed by repeated chromatography combined with fractional crystallization allowed us to isolate seven (19a–25a) and five products (19b–23b), respectively. Structural determinations of these compounds revealed that the barrelene skeleton was mainly rearranged. Alcohol 24a and ketone 25a are secondary products and arise from 21a and 22a. However, high temperature (77 °C) bromination of compounds 18a and 18b gave only nonrearranged products 19 and 20 whose barrelene skeletons were preserved. It is our conclusion that the low temperature reaction is ionic, where in the high temperature reaction radical intermediates are involved. The mechanism for the formation of the products is discussed and is supported by computational calculations. The structures of 21, 22 and 23 revealed that bromine approachs the double bond from the endo-face of the π-system. The reaction of 18a with m-chloroperbenzoic acid gave only endo-epoxide 40, which in turn supports also the endo-selectivity of the double bond in 18a and 18b.

Unusual bicyclic endoperoxides containing pyridazine ring: Reaction of unsaturated bicyclic endoperoxides with dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate

Abstract Unsaturated bicyclic endoperoxides were reacted with dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate. The Diels-Alder addition products 6–10 were isolated and characterized. The primary formed addition products gave the corresponding 1,4-dihydropyridazine derivatives upon extrusion of nitrogen. Pyridazine endoperoxides were synthesized by oxidation of the corresponding 1,4-dihydropyridazine derivatives with PIFA.

Synthesis of cycloheptane-1,2,3,4-tetraols as cyclitol mimetics

Acidic hydrolysis and acetylation of epoxidation products 11a/b of 1,4-diacetoxy-2-cycloheptene afforded unsymmetrical 1,2,3,4-tetraacetoxycycloheptane (12). OsO4-cis-hydroxylation and acetylation of 1,4-diacetoxy-2-cycloheptene gave two symmetrical 1,2,3,4-tetraacetoxycycloheptanes (14/15). Deacetylation of 1,2,3,4-tetraacetoxy cycloheptanes gave cycloheptane-1,2,3,4-tetraols as cyclitol mimetics.

A facile one-pot method to synthesise 2-alkylated indole and 2,2′-bis(indolyl)methane derivatives using ketones as electrophiles and their anion sensing ability

Indole derivatives are of great importance because of their biological activity and application in technology. This study explores the synthesis of 2-alkylated indoles derivatives and 2,2′-bis(indolyl)methanes, and their application in anion sensing. The synthesis of a wide range of 2-alkylated indoles and some 2,2′-bis(indolyl)methanes, which cannot be synthesized by previously reported methods, was for the first time accomplished employing dipole exchange of the indole ring towards electrophilic substitution. Some of the indole derivatives exhibited selective recognition and sensing ability towards F− and HSO4− anions through naked-eye detectable color changes. The sensing details of the indole derivatives were also evaluated using UV-Vis spectroscopy and 1H NMR titration techniques.

Bismuth nitrate-promoted disproportionative condensation of indoles with cyclohexanone: a new-type azafulvenium reactivity of indole

The indole nucleus is a privileged heterocyclic scaffold, which is present in several natural and synthetic compounds. New synthetic strategies to access functionalized indoles have therefore attracted the attention of both synthetic and medicinal chemists over the decades. In this study, the bismuth nitrate-promoted disproportionative condensation of indoles with cyclohexanone in one pot, to yield C3-cyclohexyl substituted indoles and 1,3-di(1H-indol-3-yl)benzene derivatives is reported for the first time. Using 3-methylindole with cyclopentanone, cyclohexanone, and cycloheptanone results in new and different synthetic pathways. The plausible reaction mechanisms are presented and supported with DFT (M06-2X/6-31+G(d,p)) calculations.

Access to C5-Alkylated Indolines/Indoles via Michael-Type Friedel–Crafts Alkylation Using Aryl-Nitroolefins

A straightforward synthetic route toward C5-alkylated indolines/indoles has been developed. The strategy is composed of Zn(OTf)2-catalyzed Friedel-Crafts alkylation of N-benzylindolines with nitroolefins, and a series of diverse indolines was first obtained in up to 99% yield. This reaction provides a direct and practical route to a variety of the C5-alkylated indolines which were also utilized for accessing corresponding indoles. Indoline derivatives with free NH groups could be obtained through an N-deprotection reaction. Moreover, the primary alkyl nitro groups in both indolines and indoles are amenable to further synthetic elaborations, thereby broadening the diversity of the products.