Hindawi Publishing Corporation International Journal of Carbohydrate Chemistry Volume 2013, Article ID 340546, 7 pages http://dx.doi.org/10.1155/2013/340546 Research Article Efficient Synthesis of Dispiropyrrolidines Linked to Sugars Sirisha Nallamala and Raghavachary Raghunathan Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai 600 025, India Correspondence should be addressed to Raghavachary Raghunathan; [email protected] Received 22 June 2013; Revised 16 September 2013; Accepted 17 September 2013 Academic Editor: J. F. Vliegenthart Copyright © 2013 S. Nallamala and R. Raghunathan. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. An expedient method for the synthesis of glyco-dispiropyrrolidines is reported through 1,3-dipolar cycloaddition reaction (1,3 DC reaction). The novel glycosyl dipolarophiles derived from D-glucose underwent neat [3+2] cycloaddition reaction with the azomethine ylides generated from 1,2-diketones and sarcosine to give the corresponding glycosidic heterocycles in good yields. 1. Introduction of heterocyclic units in a highly region- and stereoselective manner [25, 26]. In particular, the chemistry of azomethine Carbohydrates and their derivatives which are potential ylideshasgainedsignificanceinrecentyearsasitservesasan useful substrates in chemical and biological fields [1, 2]are expedient route for the construction of nitrogen-containing present in natural products [3, 4]. Recent studies on these five membered heterocycles [27, 28]. This method is widely glycomolecules [5, 6], such as proteoglycans, glycoproteins used for the synthesis of natural products such as alkaloids [7, 8], glycolipids [9, 10], and antibiotics, have shed light on and pharmaceuticals [29, 30]. the significance of carbohydrate parts (glycons) in molecular Continuing our interest in the area of 1,3-dipolar cycload- recognition for the transmission of biological information dition reaction [31, 32]andpromptedbyreportsonthe [11, 12]. Therefore, it is now recognized that carbohydrates structural features and biological activity of carbohydrates are at the heart of a multitude of biological events. With and spiropyrrolidines, we contemplated fusing structurally this stimulating biological background, efficient synthesis of unique spiropyrrolidine motifs with properly functionalized not only carbohydrates themselves but also carbohydrate- glycoside derivatives, on the assumption that fusion might containing heterocycles is becoming more and more impor- lead to a new class of carbohydrate-based heterocycles with tant in the field of organic chemistry and chemical biology potential biological activities. Towards this end, we report, [13]. Hence there has been renewed interest in the synthesis for the first time, a simple and short approach to a new of carbohydrate-based heterocycles. series of sugar-fused dispiropyrrolidines by using sarcosine Heterocyclic compounds, particularly five and six mem- and 1,2-di/tri ketones (isatin/ninhydrin/acenaphthoquinone) bered ring compounds, have occupied a prominent place to generate azomethine ylide that reacts with sugar-derived among the organic compounds in view of their diverse precursors. biological activities [14–18]. The spiropyrrolidine ring sys- tems [19, 20] have acquired a prominent place among 2. Materials and Methods various heterocyclic compounds owing to their presence 2.1. General Considerations. IR spectra were recorded on a in many pharmacologically relevant alkaloids, as typified 1 by rhyncophylline, corynoxeine, mitraphylline, horsifiline, SHIMADZU 8300 series FT-IR instrument. HNMRspectra and spirotryprostatins [21–23]. Synthesis and bioactivities of were recorded in CDCl3 using TMS as an internal standard 13 some of the spiropyrrolidines were reported by us recently on a Bruker 300 spectrometer at 300 MHz. CNMRspectra [24]. Multicomponent intermolecular 1,3-dipolar cycloaddi- were recorded on a Bruker 300 spectrometer at 75 MHz. Mass tion reaction is an efficient method for the construction spectra were recorded using Thermo Finnigan (LCQ) Amax 2 International Journal of Carbohydrate Chemistry 6000 ESI mass spectrometer. Elemental analysis was carried 2.4. Dihydrogen(3 S)-3 -[(3 aR,5 R,6 S,6 aR)-6 -(benzyloxy)- out using Perkin-Elmer CHNS 2400B instrument. tetrahydrospiro[cyclohexane-1,2 -furo[2,3-d][1,3]dioxole]-5 - yl]-1,1 ,5-trimethyl-1 ,3 -dihydrodispiro[1,5-diazinane-3,4 - pyrrolidine-2 ,2 -indene]-1 ,2,3 ,4,6-pentone (13). Colour- 2.1.1. Representative Procedure for the Synthesis of Dipolaro- ∘ less powder. Yield; 60%. m.p: 94 C.IR(KBr);1672,1719,1720, phile Glycosylidene N,N-Dimethyl Barbituric Acid 8. To a −1 1 6 1732, 1734 cm : H NMR (CDCl3,300MHz); 1.45–1.62 stirred solution of sugar aldehyde (1 mmol) and N,N- = 8.4 dimethyl barbituric acid (1 mmol) in ethanol (10 mL), triethy- (m, 10 H), 2.10 (s, 3 H), 2.41 (d, Hz, 1 H), 2.59 (d, = 8.4 Hz, 1 H), 3.19 (s, 6 H), 3.32 (d, = 7.2 Hz, 1 H), 3.81 lamine (1 mmol) was added at room temperature and stirring = 3.6 =12 was continued for 4 h. After completion of the reaction, (dd, ,7.2Hz,1H),4.12(d, Hz,1H),4.61–4.65 (m,3H),6.02(d, = 3.6 Hz,1H),6.79–7.84(m,9H). the reaction mixture was poured into the ice water (5 mL) 13 and sticky solid was formed which was extracted with ethyl C NMR (75 MHz); ppm 22.59, 22.91, 24.22, 28.87, 28.96, acetate (3×20mL). The organic phase was successively 35.47, 36.12, 37.48, 42.37, 44.22, 56.34, 68.39, 71.09, 77.49, 80.79, 82.03, 104.87, 113.52, 117.39, 118.07, 122.19, 122.79, 125.79, washedwithbrine(15mL)anddriedoveranhydrousNa2SO4. 126.49, 127.30, 127.82, 129.56, 131.23, 135.92, 138.19, 160.27, The solvent was removed under reduced pressure to give the / + +1 crude product, which was purified by column chromatogra- 164.21, 164.54, 196.32, 196.91. MS (ESI); 644.2 (M ). phy using hexane and ethyl acetate and (8 : 2) as eluent to Anal. Calcd for; C35H37N3O9;C,65.31;H,5.79;N,6.53%. afford the corresponding dipolarophile in good yields. Found;C,65.37;H,5.84;N,6.48%. 2.5. Dihydrogen(1S,3 S)-3 -[(3 aR,5 R,6 S,6 aR)-6 -(benzyl- 2.2. 5-[(3 aR,5 R,6 S,6 aR)-6 -(Benzyloxy)-tetrahydrospiro- oxy)-tetrahydrospiro[cyclohexane-1,2 -furo[2,3-d][1,3]dioxo- [cyclohexane-1,2 -furo[2,3-d][1,3]dioxole]-5 -ylmethylidene]- le]-5 -yl]-1 ,1 ,5 -trimethyl-2H-dispiro[acenaphthylene-1, 8 1,3-dimethyl-1,3-diazinane-2,4,6-trione ( ). Colourless pow- 2 -pyrrolidine-4 ,3 -[1,5]diazinane]-2,2 ,4 ,6 -tetrone (15). ∘ 1 ∘ der. Yield 70%. m.p; 112 C. H NMR (CDCl3,300MHz); Colourless powder. Yield; 59%. m.p; 58 C. IR (KBr); 1674, 1.42–1.64 (m, 10 H), 3.02 (s, 6 H), 3.72–3.82 (m, 2 H), 4.09 −1 1 1720, 1722, 1728 cm . H NMR (CDCl3,300MHz); (d, =12Hz,1H),4.45–4.54(m,2H),5.96(d, = 3.6 Hz, 13 1.49–1.62 (m, 10 H), 2.08 (s, 3 H), 2.32 (d, =8.7Hz, 1 H), 1 H), 7.03–7.20 (m, 5 H), 7.32 (s, 1 H). C NMR (75 MHz); 2.58 (d, = 8.7 Hz, 1 H), 3.11 (s, 6 H), 3. 43 (d, = 6.9 Hz, ppm 22.79, 23.17, 25.30, 28.17, 28.37, 35.81, 36.17, 63.51, 70.41, 1 H), 3.88 (dd, = 3.6, 6.9 Hz, 1 H), 4.09 (d, = 11.7 Hz, 1 H), 72.40, 80.14, 83.34, 105.43, 114.41, 127.40, 128.64, 128.42, 4.58–4.64 (m, 3 H), 5.98 (d, = 3.6 Hz, 1 H), 6.67–8.04 (m, 129.92, 137.41, 147.49, 157.42, 160.93, 161.41. MS (ESI); / 13 + +1 11 H). C NMR (75 MHz); ppm 23.12, 23.79, 23.54, 28.72, 457.2 (M ). 28.84, 35.52. 36.49, 37.84, 40.29, 42.52, 56.13, 67.97, 70.98, 78.03, 81.64, 82.44, 105.47, 114.02, 118.39, 119.42, 121.31, 122.48, 2.2.1. General Procedure for Synthesis of Cycloadducts (11, 13, 122.79, 125.54, 126.17, 126.54, 127.41, 129.41, 130.32, 131.42, 15 9 12 135.42, 139.39, 140.42, 159.97, 163.54, 163.88, 192.39. MS (ESI); ). To a mixture of isatin /ninhydrin /acenaphthenequi- + none 14 (1 mmol) and sarcosine 10 (2 mmol), glycosylidene / 666.4 (M +1). Anal. Calcd for; C38H39N3O8;C,68.56; N,N-dimethyl barbituric acid 8 (1.0 mmol) was added and H,5.90;N,6.31%.Found;C,68.63;H,5.94;N,6.25%. heated under reflux in methanol (20 mL) until the disap- pearance of the starting materials as evidenced by TLC. The 3. Results and Discussion solvent was removed under vacuo. The crude product was subjected to column chromatography using petroleum ether- As shown in Scheme 1, the construction of a sugar-fused ethyl acetate as eluent. dispiropyrrolidine ring system in 3 was envisaged from a [3+2] cycloaddition reaction involving an azomethine ylide with an olefin, while templates for such cycloaddition could 2.3. Dihydrogen(2 S,3 S)-3 -[(3 aR,5 R,6 S,6 aR)-6 -(benzyl- be conveniently realized from dicyclohexylidine glucose 1. oxy)-tetrahydrospiro[cyclohexane-1,2 -furo[2,3-d][1,3]dioxo- 1 le]-5 -yl]-1,1 ,5-trimethyl-1 ,2 -dihydrodispiro[1,5-diazinane- Accordingly, O-alkylation of with benzyl bromide in the 4 3,4 -pyrrolidine-2 ,3 -indole]-2,2 ,4,6-tetrone (11).