No abstract

A series of novel quinoline-based tetracyclic ring-systems were synthesized and evaluated in vitro for their antiplasmodial, antiproliferative and antimicrobial activities. The novel hydroiodide salts 10 and 21 showed the most promising antiplasmodial inhibition, with compound 10 displaying higher selectivity than the employed standards. The antiproliferative assay revealed novel pyridophenanthridine 4b to be significantly more active against human prostate cancer (IC50 = 24 nM) than Puromycin (IC50 = 270 nM) and Doxorubicin (IC50 = 830 nM), which are used for clinical treatment. Pyridocarbazoles 9 was also moderately effective against all the employed cancer cell lines and moreover showed excellent biofilm inhibition (9a: MBIC = 100 µM; 9b: MBIC = 100 µM).

Substrate selectivity is an important output function for the validation of different enzyme models, catalytic cavity compounds, and reaction mechanisms as demonstrated in this review. In contrast to stereo-, regio-, and chemoselective catalysis, the field of substrate-selective catalysis is under-researched and has to date generated only a few, but important, industrial applications. This review points out the broad spectrum of different reaction types that have been investigated in substrate-selective catalysis. The present review is the first one covering substrate-selective catalysis and deals with reactions in which the substrates involved have the same reacting functionality and the catalysts is used in catalytic or in stoichiometric amounts. The review covers real substrate-selective catalysis, thus only including cases in which substrate-selective catalysis has been observed in competition between substrates.

The synthesis of two polyhydroxylated pyrrolidines as 1,4-dideoxy-1,4-imino- d -arabinitol (DAB) analogues bearing a hydrazide moiety is described. The DAB analogues act as selective and potent inhibitors of α-mannosidase in the submicromolar concentration ranges ( K i values ranging from 0.23 to 1.4 μM).

(3R,4R,5R)-2-Imino-3,4-dihydroxy-5-hydroxymethylpiperidine hydrocloride or isofagomidine was synthesized from D-arabinose in 12 steps and an overall yield of 9.9%. The synthesis proceeded by introduction of an aminomethyl group in the 4-position of D-arabinose and conversion of C-1 into a nitrile. The key step in the synthesis was a copper-catalyzed cyclization of aminonitrile to amidine. Isofagomidine was a potent α-mannosidase inhibitor (K(i) = 0.75 μM).