Namudar I. Kurbanoglu

Carbonic anhydrase inhibitors: inhibition of human and bovine isoenzymes by benzenesulphonamides, cyclitols and phenolic compounds

Carbonic anhydrase inhibitors (CAIs) are a class of pharmaceuticals used as anti-glaucoma agents, diuretics and anti-epileptics. We report here the inhibitory capacities of benzenesulphonamides, cyclitols and phenolic compounds 1–11 against three human CA isozymes (hCA I, hCA II and hCA VI) and bovine skeletal muscle carbonic anhydrase III (bCA III). The four isozymes showed quite diverse inhibition profiles with Ki values ranging from low micromolar to millimolar concentrations against all isoenzymes. Compound 5 and 6 had more powerful inhibitory action against hCA I and very similar action against hCA II and hCA VI as compared with acetazolamide (AZA) and sulphapyridine (SPD), specific CAIs. Probably the inhibition mechanism of the tested compounds is distinct of the sulphonamides with RSO2NH2 groups and similar to that of the coumarins/lacosamide, i.e. binding to a distinct part of the active site than that where sulphonamides bind. These data may lead to drug design campaigns of effective CAIs possessing a diverse inhibition mechanism compared to other sulphonamide/sulphamate inhibitors.

Asymmetric reduction of substituted acetophenones using once immobilized Rhodotorula glutinis cells

The asymmetric reductions of acetophenone and its analogues using once immobilized Rhodotorula glutinis cells were studied. The performance and reaction parameters of the immobilized cells were also investigated and it was determined that the cells could be used 15 times in batch processes. All chiral alcohols obtained using purification procedures were of sufficient enantiopurity (>99%) of the (S)-enantiomer. The applicability of the optimized process for a preparative scale bioreduction was shown. Under the optimum conditions, 35mM (4.3g) of the product ((S)-1-phenylethanol) was produced from 45mM (5.4g) of the substrate (acetophenone) with one time immobilized R. glutinis EBK-2 cells (6g wet weight). The yield was calculated as 77%. In this study, it was found that the buffer level had a very significant effect on the reaction activity. Our results demonstrate that the optimized process can be implemented on a preparative scale.

Production of (R)-1-phenylethanols through bioreduction of acetophenones by a new fungus isolate Trichothecium roseum.

A total of 120 fungal strains were isolated from soil samples and evaluated in the bioreduction of substituted acetophenones to the corresponding (R)-alcohols. Among these strains, isolate Trichothecium roseum EBK-18 was highly effective in the production of (R)-alcohols with excellent enantioselectivity (ee > 99%). Gram scale preparation of (R)-1-phenylethanol is reported.

Stereospecific synthesis of a new N-tosyl bromo-aminocyclitol

Aminocyclitols are cyclic polyhydroxylated amines formally derived from cyclitols, and they constitute an important class of biologically active compounds. In the current research, the synthesis and characterization of a new N-tosyl bromo-aminocyclitol 8 starting from cyclohexadiene were carried out. In accordance with this purpose, the oxazolidinone 13 was prepared by the palladium-catalyzed reaction of bis-carbamate 12, synthesized from cyclohexenediol, derived in two steps from cyclohexadiene. Hydrolysis of 13 was achieved with methanolic potassium carbonate to afford 14 and ketalization gave 18 with good yield. Allylic bromination of 18 gave compound 19. Bromination was conducted with N-bromosuccinimide in the presence of a catalytic amount of benzoyl peroxide. Osmylation of the double bond and acid-mediated acetonide removal of 19 gave N-((1S,2R,3R,4S,6S)-4-bromo-2,3,6-trihydroxycyclohexyl)-4-methylbenzenesulfonamide 8. This molecule may also be evaluated for its biological activity.Graphical abstract