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The tandem hydroamination-annulation reaction of 4-pentynenitriles in the presence of amine nucleophiles and a cooperatively operating catalyst system, consisting of Ph 3 PAuCl and Zn(ClO 4 ) 2 , provides an efficient route to 2-aminopyrroles. Two regioisomeric 2-aminopyrroles were formed in moderate to good yields.Over the past six years, gold catalysis has shown to be a powerful tool in organic synthesis. Cationic gold(I) and gold(III) complexes show unique behavior towards unactivated alkenes, alkynes, allenes, 1,3-dienes, and enynes promoting the nucleophilic addition of a variety of functional groups both inter-and intramolecularly.1 In that respect, a great number of gold catalyzed tandem reactions of various systems with external nucleophiles that enable the formation of cyclic systems are present in the literature.2 Especially those transformations including the catalytic addition of N-H bonds across C-C multiple bonds (hydroamination) that are catalyzed by both gold(I) and gold(III) complexes have found wide application for the generation of new C-N bonds 3,4 affording nitrogen containing heterocycles, such as pyrroles and pyridines.Among the various synthetic strategies, catalytic transformations that use transition-metal catalysts are one of the modern approaches for forming pyrroles. 5 Relatively few examples of the gold-catalyzed synthesis of highly substituted pyrroles have been reported, however. 4e,6 In the course of our research to develop new methodologies for the synthesis of nitrogen containing heterocycles that are promoted by transition metal catalysts, we recently demonstrated Zn(II) salts to be effective catalysts for the activation of the CQO bond and CN triple bond.7 These principles led us to the discovery of a novel catalytic one-pot synthesis of 2-aminopyrroles starting from a-cyanomethyl-b-ketoesters. Zinc perchlorate smoothly catalyzes the amination of nitriles, and the subsequent cyclocondensation affords five-membered rings (pyrroles) in good yield, as exemplified in the conversion of 1 to 2 and 3 (Scheme 1). 7a

A novel series of 8-substituted coumarin-based compounds, characterized by the presence of alkylpiperazine and arylpiperazine chains, were synthesized and tested for their inhibitory activity against four human carbonic anhydrase (hCA) isoforms. All compounds displayed nanomolar potency against the cancer-related hCA IX and hCA XII; moreover, they were shown to be devoid of any inhibitory activity toward the cytosolic hCA I and hCA II up to 10 µM concentration in the assay system. Therefore, the synthesized coumarin ligands demonstrated to be potent and selective hCA IX/XII inhibitors, and were shown to be as potent as the reference inhibitor acetazolamide against hCA XII, with single-digit nanomolar Ki values. Molecular modeling studies provided a rationale for explaining the selectivity profile of these non-classic hCA inhibitors and their interactions with the enzymes, according to their specific mechanism of action, thus paving the way for future structure-based lead optimization studies.

Coumarins (2H‐1‐benzopyran‐2‐one), derivatives that can be isolated from several plants, have been reported for their anticoagulant, antimicrobial, anti‐inflammatory, or anticancer activity. Some of these structures are currently approved for the treatment of cardiovascular diseases, as antibiotics or as an anticancer drug. Given the great potential of this structure and the limited number of studies that focus on molecules derived from carbon 8 of the benzopyranone heterocycle, we synthesized in this project 38 coumarin derivatives by substituting carbon 8 of the benzopyran ring with some aromatic and aliphatically substituted piperidines and piperazines. As a few of these structures were already shown to exhibit some carbonic anhydrase (CA) inhibition and as CA enzymes are reported to be closely related to inflammation, the synthesized derivatives were evaluated for their anti‐inflammatory activity in vitro. The results indicated that compounds 20 and 31 revealed promising anti‐inflammatory activity, as they demonstrated better activity than the reference drugs.