Synthesis and antibacterial activity of novel 7-(3-substituted-3 or 4-trifluoromethyl-1-pyrrolidinyl)-8-methoxyfluoroquinolones

Diastereodivergent Asymmetric 1,3‐Dipolar Cycloaddition of Azomethine Ylides and β‐Fluoroalkyl Vinylsulfones: Low Copper(II) Catalyst Loading and Theoretical Studies

“…Although the catalyst loading could be further decreased to 0.5 mol %, al oading of 2.5 mol %w as used for the substrate scope exploration for experimental convenience.T he use of other potential Lewis acid catalysts such as Cu(CH 3 CN) 4 BF 4 ,N i(OAc) 2 ,a nd AgOAc provided inferior results in this 1,3-dipolar cycloaddition (entries [10][11][12]. Gratifyingly,t he asymmetric induction for the exo-product was substantially increased when the glycine iminoester 2b (R = t Bu) was used instead of 2a at 0 8 8C(dr = 41:1, er = 94:6;entry 4).…”

“…[5] Despite these tremendous advances,t he known synthetic methods still suffer from various problems,such as:1)high catalyst loading (at least 5mol %);2 )rarely using cheaper and more stable Cu II catalysts in contrast to Cu I catalysts; [6] 3) few examples of providing exo'-adducts as the major isomers; [7] 4) limited trifluomethylated starting materials. [9] Among various fluoroalkyl groups,t he trifluoromethyl group (CF 3 )h as received significant attention because of its similar size to the methyl group and its high electronegativity resulting in unique stereoelectronic properties,w hich may substantially increase the metabolic stability,l ipophilicity,a nd thus bioavailability of drug molecules.I ndeed, an umber of CF 3 -substituted pyrrolidines displaying interesting bioactivities have been reported, including the insecticide A, [10] suicide inhibitor B, [11] antibacterial agent C, [12] and hepatitis Cv irus inhibitor D [13] ( Figure 1). [9] Among various fluoroalkyl groups,t he trifluoromethyl group (CF 3 )h as received significant attention because of its similar size to the methyl group and its high electronegativity resulting in unique stereoelectronic properties,w hich may substantially increase the metabolic stability,l ipophilicity,a nd thus bioavailability of drug molecules.I ndeed, an umber of CF 3 -substituted pyrrolidines displaying interesting bioactivities have been reported, including the insecticide A, [10] suicide inhibitor B, [11] antibacterial agent C, [12] and hepatitis Cv irus inhibitor D [13] ( Figure 1).…”

Recent Advances in Organocatalyzed Domino C–C Bond-Forming Reactions

“…Substituted pyrrolidines are found in many bioactive natural products and pharmaceutical agents [ 21 , 22 ]. Particularly, the addition of the trifluoromethyl group to these pyrrolidines makes them attractive targets for synthetic organic chemists [ 23 , 24 ]. This methodology provides a synthesis of chiral trifluoromethylated pyrrolidines with good yield and excellent diastereoselectivity and enantioselectivity.…”

Quinolone Compounds with Activity Against Multidrug-Resistant Gram-Positive Microorganisms

“…The most famous modifications of the 8 position of the quinolone are X = CH or N (naphthyridines). However, compact and lipophilic groups: X = CR 8, where R 8 = fluorine [16,17,25,54], trifluoromethyl [52] and methoxy [22,55] have gained ground due to the positive influence they have on the antibacterial activity. Table 10.…”

“…The compounds containing a chlorine atom in 8 position [30,25,17] are very active, as well as analogs containing fluorine or methoxy moiety [22,55]. The introduction of bulky substituents, e.g., ethyl, reduces the antibacterial activity against gram negative (if a comparison with 8methoxy-quinolones is made).…”