Note Facile one-pot synthesis of sugar–quinoline derivatives Subbiah Nagarajan, Thangamuthu Mohan Das * Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai 600 025, India article info Article history: Received 18 February 2009 Received in revised form 5 March 2009 Accepted 9 March 2009 Available online 12 March 2009 Keywords: Quinoline derivatives C-b-Glycosides Friedländer condensation Sugar derivatives abstract Seven different sugar–quinoline derivatives were synthesised in a ‘one-pot’ reaction from their corre- sponding C-b-glycoside derivatives. The compounds were characterised by NMR spectroscopy and ele- mental analysis. Ó 2009 Elsevier Ltd. All rights reserved. The chemistry of nitrogen heterocycles, viz. lactam, 1,2 pyrrole, 3,4 indole 5,6 and quinoline 7,8 derivatives, has been extensively devel- oped for more than 100 years due to the diversity of biological activities and pharmaceutical applications found among these compounds. 2-Arylated quinolines are present in nature and occur in the structures of 5-lipoxygenase inhibitors, 9 leucotriene antago- nists, 10 LTD4 receptor antagonists 11 and other biologically active molecules. In particular, quinoline derivatives have been found to act as antimalarial, 12–14 antibacterial, 15 antiasthmatic, antihyper- tensive and anti-inflammatory 16 drugs. Quinolines are also impor- tant components in industrial antioxidants and dyes. In addition to medicinal and industrial applications, polyquinolines are found to undergo hierarchical self-assembly into nano- and meso-structures with enhanced electronic and photonic properties. 17,18 In its origi- nal form for the synthesis of quinoline derivatives, the Friedländer synthesis consisted of a reaction between an aromatic o-aminoal- dehyde and an aldehyde or ketone bearing an a-CH 2 functionality. Thus, new synthetic routes to quinolines could have major impact on the potential applications of these useful compounds. 4,6-O-Butylidene-D-glucopyranose was synthesised from D- glucose by adopting a procedure reported in the literature. 19,20 C-b-Glycosidic ketones 2a–g were synthesised by the Knoevena- gel condensation of 2,4-pentanedione with sugar derivatives, such as 4,6-O-butylidene-D-glucopyranose, D-glucose, D-xylose and D-galactose. 21–23 Although the synthesis of C-b-glycosidic ke- tones of peracetylated derivatives is described in the litera- ture, 21–23 in the present report, we have extended the methodology to partially protected sugar derivatives. Among many alternative routes to quinoline and substituted quinolines, their synthesis using the Friedländer method seems to have cre- ated significant interest as documented by reports in the litera- ture. 24 In continuation of our ongoing research in the area of saccharide chemistry, 25 we have reported a facile one-pot syn- thesis of sugar–quinoline derivatives. In our case, we have used the protected, partially protected and unprotected C-b-glycosidic ketones for the synthesis of quinoline derivatives. Reaction of substituted 2-aminobenzaldehyde (1) with a series of C-b-glyco- sidic ketones in the presence of pyrrolidine (25%) as an organic catalyst in 1:3 CH 2 Cl 2 –MeOH resulted in a 62–85% yield of the sugar–quinoline derivatives (Scheme 1). With other bases, such as triethylamine, NaOH, KOH, piperidine and pyridine, the yields obtained were less than 40%. The structures of the resulting C-b- glycosides 2a–g were determined by 1 H and 13 C NMR spectros- copy and elemental analysis. The appearance of a peak at 2.13 ppm in the 1 H NMR spectrum and at 207 ppm in the 13 C NMR spectrum corresponds to –CH 3 and –C@O groups, respec- tively. The formation of sugar-based quinoline derivatives 3a–g was determined from the 1 H and 13 C NMR studies. The 1 H NMR spectrum of 3e notably exhibited a large coupling constant for the H-1 0 signal (J H1 0 ,H2 0 9.5 Hz), indicating a trans-diaxial ori- entation of H-1 0 , and H-2 0 as expected for a b-D-configured glu- copyranose moiety. 21 Structures of the sugar moieties, amounts of reactants, reaction conditions and product yields are given in Table 1. Thus, we have designed and synthesised quinoline–sugar deriv- atives having a methylene group that favours flexibility of the mol- ecule as is observed with sugar–b-lactam derivatives. 26 Some of the quinoline-based derivatives exhibit different biological activi- ties. 12–16 The quinoline derivatives reported in this paper may also 0008-6215/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.carres.2009.03.009 * Corresponding author. Tel.: +91 44 22202814; fax: +91 44 22352494. E-mail address: tmdas_72@yahoo.com (T.M. Das). Carbohydrate Research 344 (2009) 1028–1031 Contents lists available at ScienceDirect Carbohydrate Research journal homepage: www.elsevier.com/locate/carres