American Journal of Chemistry and Application 2015; 2(5): 66-69 Published online September 20, 2015 (http://www.aascit.org/journal/ajca) ISSN: 2375-3765

Isolation of Substituted Diaryl Dihydroxy Furo Furan from the Tree Khaya grandifolia

Jack I. R., Nwachoko N.

Department of Chemistry, Rivers State University of Science and Technology, Port Harcourt, Nigeria Email address [email protected] (Nwachoko N.)

Citation Jack I. R., Nwachoko N.. Isolation of Substituted Diaryl Dihydroxy Furo Furan from the Tree Keywords Khaya grandifolia . American Journal of Chemistry and Application . Vol. 2, No. 5, 2015, pp. 66-69. Khaya grandifolia , Abstract Meliaceae, Extraction of the powdered trunk of the tree Khaya grandifolia with ethyl acetate for Dilatol, l l 8hrs gave light oil in 1.9% yield identified as 2,6-bis(3 , 4 –dimethoxyphenyl)-3,7-dioxa Diacetate 1 13 bicyclo [3,3,0] octa-4,8-diol (5) by its spectra data such as infra red, H, C n.m.r. and mass spectrum. The diol was confirmed by its conversion to the diacetate (6). A comparison of the spectra of the dilactol (5) and the diacetate (6) with Eudesmin (1c) (table 1) corroborated evidence for the basic furofuran skeleton with slight changes in Received: August24, 2015 the chemical shifts of some of the protons and carbons. Revised: September3, 2015 Accepted: September4, 2015 1. Introduction

Interest in substituted furofuranoid continues to grow because of their occurrence, diversity and utility. Many parts of higher found in the rainy and tropical regions serve as reservoir for a number of these substituted furofurans (Pelter and Ward 1978). For example, Sesamin (1a) was isolated from the bark of Zanthoxylum acanthapoduim (Pelter et al 1976), Pinoresinol (1b) and Eudesmin (1c) have also been isolated from various pinus species and from the kinos of Australian Eucalyptus (Jack 1981). Of the hydroxy substituted lignans, Gmelinol (2a) and Arboreol (2b) were isolated from leichhardtii and Gmelina arborea respectively (Anjaneyulu et al ., 1975). We have previously reported (Jack and Orubite 2009) the isolation of a dilactone (3) from Gmelina arborea species (Keay 1989) in Nigeria. Very recently, a 1,5-dihydroxy substituted furo-furanoid (4) was isolated from the commercial timber Halleaciliata P. commonly called Abura (Jack and Nwachoko, 2015). Whereas sesamin is known to increase markedly the insecticidal potency of pyrethrum, PinoresinolDiglucose is a major antihypertensive principle of Tu-Chung bark (Wiberg and Connon 1976). Some Lignans from Aegilopsovata L with unusual features were reported to be germination inhibitors in light rather than in darkness (Cooper et al ., 1979). Other lignans such as Podophyllotoxin has been used in the treatment of malignant diseases while Steganacin is an antitumour agent. Many Africans have resorted to unorthodox medicine by drinking alcoholic extracts from leaves, bark and roots of many higher plants as remedy for various health problems. One of such trees commonly called Iroko is khaya grandifolia of the family meliaceae which grows in the fresh water areas of the Niger Delta region of Nigeria. At maturity, the tree can attain a height of over 15metres and girth of 2metres. It is of tremendous economic importance being the source of dugout canoes and also converted to pieces of furniture in the furniture industries. The aim of this study is to investigate the constituents of this tree with a view to 67 Jack I. R. and Nwachoko N.: Isolation of Substituted DiarylDihydroxyFuro Furan from the Tree Khayagrandifolia

finding out if there are lignans especially those belonging to I.R. (film) (OH) 3490 – 3455; (CH) 3015 -2900; (arom.) -1 1 the furo furan class as have been reported in other higher 1610cm . H n.m.r. (CDCl 3) H -1/5, 3.03m 2H; H – 2/6, 4.80 plants. d (6) 2H; H – 4/8, 5.42 d(4) 2H; OCH 3, 3.80s, 3.82s, 6H; 13 Table 1. 1H n.m.r. spectra *. OH, 5.80, 2H; arom. 6.70 – 7.10m, 6H. C n.m.r.(CDCl 3)OCH 3, 55.94, 55.68; C – 1/5, 59.80; C – 2/6, Chemical shifts in δ (ppm) I II I II Protons 85.24; C – 4/8, 102.42; C – 2 /2 107.28; C – 5 /5 , 107.94; C (1c) (5) (6) – 6I/6 II , 108.20; C – 1I/1 II , 136.80; C – 3I/3 II , 147.40; C – H – 1/5 3.15m 3.03m 3.05m I II H – 2/6 4.75 d (4) 4.80 d (6) 4.82 d (6) 4 /4 , 148.10 H – 4a/8a 3.80 – 4.00 m Diacetate (6) 5.42 d (4) 2H 5.48 d 2H H – 4e/8e 4.20 – 4.40 m 1.2g of (5) was dissolved in 10ml of dry pyridine and 5ml OCH 3 3.86 s, 3.90 s 3.80 s, 3.82 s 3.82 s, 3.84 s of dry acetic anhydride was added and stirred at room OAc - - 2.20 s temperature for 8hrs. The mixture was poured into 50mls of OH** - 5.80 - Arom. 6.80 – 7.00 m 6.70 – 7.10 m 6.72 – 7.20m ice cold water and left to stand for 30minutes. It was extracted with ethyl acetate (40ml x 3), washed with *Spectra run in CDCl 3 saturated NaHCO 3 (40ml x 3), 1M HCl (40ml x 2) then with ** Signal disappeared on D 2O shake water (30ml x 2) and dried over anhydrous MgSO 4. Table 2. 13 C n.m.r spectra*. Evaporation of the solvent gave an oil. Yield 2.0g (60% Th) Chemical shift in ppm Carbon I.R. (film) (CH) 3080 – 2905; (OAc) 1765; (arom.) 1c (5) (6) -1 I C-1} 1605cm , H n.m.r. (CDCl 3) H -1/5, 3.05m; 2H; H – 2/6, 4.82 54.31 59.80 62.48 C-5 d(6) 2H; H -4/8, 5.48 d 2H; OCH 3, 3.82 s, 3.84s 6H; OAc, C-4} 13 71.72 102.42 103.20 2.20s 6H; arom. 6.72 – 7.20 m 6H. C n.m.r. (CDCl 3) OCH 3, C-8 56.60, 56.34;C – 1/5, 62.48; C -2/6, 85.60; C – 4/8, 103.20; C C-2} 85.77 85.24 85.60 – 2I/2 II 108.00; C – 5I/5 II , 108.62; C – 6I/6 II , 108.94; C -1I/1 II C-6 I II I II C-1I} 136.90; C – 3 /3 , 148.50; C – 4 /4 , 148.70; OAc, 168.95. 134.04 136.80 136.90 .+ C-1II Mass spect.m/e 502(35%) M C-3I 3II 148.85 147.40 148.50 C-4I 4II 149.46 148.10 148.70 C-2I 2II 109.67 107.28 108.00 3. Results and Discussion C-5I 5II 111.45 107.94 108.62 Table 3. C-6I6II 118.36 108.20 108.94 Mass spectra.

OCH 3 55.90; 55.57 55.94; 55.68 56.60; 56.34 OAc - - 168.95

*Spectra run in CDCl 3

2. Materials and Methods Infra red spectra were recorded on PyeUnicam SP 1050 Spectrophotometer. Mass spectra were obtained on an AET, MS9 double focussing instrument at 250 oC and 70eV. lH and 13 C decoupled n.m.r. spectra were run from Varian HA100 and XL100 spectrophotometers respectively in CDCl 3 using TMS as an internal standard. Chemical shifts are given as δ(ppm). Thin layer chromatography (Tlc) was run or silica gel GF254 plates using toluene ethyl acetate 5:1. All reagents and solvents were purified before use. Extraction of the trunk of Khaya grandifolia The trunk of Khaya grandifolia obtained from Ahoada in Rivers State was chopped into stripes sundried and ground Examination of the ethyl acetate extract of the powdered into a powder. 250g of the powder was put into a soxhlet trunk by t.l.c. showed predominantly one spot with R . 0.48 extractor and extracted with ethyl acetate for 8hrs. The ethyl f and a base line material. The spot having R . 0.48 gave one acetate extract 1litre was distilled off leaving a dark brown f product(5) on work up (see experimental) and was identified sticky oil. This oil was washed with chloroform (20ml x 3), on the basis of its spectral data as 2,6-bis(3 l,4 l– dried over anhydrous MgSO and evaporated to give 4.8g of 4 dimethoxyphenyl)-3,7-dioxa bicyclo [3,3,0] octa-4,8-diol. light oil leaving a very dark gum as baseline material. The structure of (5) was confirmed by converting it to the Yield 4.8g(1.9% Th.) American Journal of Chemistry and Application 2015; 2(5): 66-69 68

diacetate (6) by acetylation with acetic anhydride and δ5.42 as doublet with coupling constant of 4. The pyridine. The infra red spectrum of (5) gave bands at 3490 – position of the hydroxy groups in (5) is further 3455 and 1610cm -1 indicative of hydroxyl group and an confirmed on acetylation to give the diacetate (6) aromatic moiety respectively. The mass spectrum did not whence the OH signal is replaced by the acetoxy group show a molecular ion as is the case with many hydroxy and caused a further shift of H- 4/8 to δ5.48 as doublet compounds (Finar 2003) but the spectrum was dominated by due to the anisotropic effect of the carbonyl of the fragment ions such as m/e 167, 166, 165, 163 and 137 which acetoxy group. The benzylic H- 2/6 and aromatic only give information relating to the aromatic group (see protons are not much affected as they appear in the table 3). The ion at m/e 193 is significant and is a expected region of the spectrum. consequence of a vertical cleavage of the dilactol (5) on The 13 C (n.m.r.) spectra of (5) and (6) (table 2) present either side. For the diacetate (6), there is a large molecular interesting features. C – 1/5 in Eudesmin (1c) for instance are ion at m/e 502 (35%) which readily lost two molecules of moved down field from 54.31 by 5.51ppm and 8.17ppm to acetic acid to yield the ion at m/e 382 (15%). This 59.80 and 62.48ppm respectively in the dilactol (5) and fragmented to give the characteristic ions at m/e 235, 193, diacetate (6). The C- 4/8 is similarly affected by shifting from 175, 165 and 137 (see also table 3). 71.92 to 102.42ppm in the dilactol and 103.20ppm in the • The proton magnetic resonance spectrum of (5) shows diacetate. A combination of these spectra data confirms the clearly, the preservation of the furofuran nucleus as in structures of the dilactol and diacetate as (5) and 6 (1c) with the methine H–1/5, benzylic H-2/6 and respectively. aromatic protons appearing at the usual places in the spectrum (see table 1). The presence of two hydroxy Acknowledgement groups which occurred at δ5.8 is inferred by the integration for two protons and the disappearance of the We wish to express our thanks to Prof. B Green of the signal on D 2O shake. Furthermore, the methylene Department of Environmental Biology of the Rivers State protons H–4/8 which normally appear as two distinct University of Science and Technology for identifying the sets of four protons as multiplets in Eudesmin (1c) are tree. We also thank Mr. Christian Oganuzo of Obele town seen as one set of two protons due to their coupling to Ahoada L.G.for supplying us the sample. the hydroxy group. These protons are now shifted to

1.-4 are diaryl substituted furo furans, 5 and 6 are conversion ofdilactol to the diacetate. 69 Jack I. R. and Nwachoko N.: Isolation of Substituted DiarylDihydroxyFuro Furan from the Tree Khayagrandifolia

[6] Jack, I.R. and Nwachoko, N. (2015).Lignans from the commercial timber Halleaciliata P. commonly called Abura . References American Journal of Chemistry and Application 2 (3), 17-20. [1] Anjaneyulu, A.S.R.,JaganmohanRao, K., KameswaraRao, V., [7] Keay, R.W.J. (1989).Trees of Nigeria. (Publisher Clarendon Ramachandra, R. L. and Subrahmanyam, C. (1975).The Press Oxford) 437-438. structures of lignans from Gmelinaarborea Linn. Tetrahedron, 31 , 1277-1285. [8] Pelter, A.,Ward, R.S.,VenkataRao, E. and Sasthry, K.V. (1976).Sesamin from [2] Cooper, R.,Gottlieb, H.E., Lavie, D. and Levy, E.C. Zanthoxylumacanthapodium .Tetrahedron 32 , 2783. (1979).Lignans from Aegilopsovata L. Tetrahedron, 35 , 861- 868. [9] Pelter, A. and Ward, R.S. (1978). Chemistry of Lignans(Ed. Rao, C.B.S. Andra University Press, India) ch.7. [3] Finar, I. L. (2003).Organic Chemistry, Fundamentals and Principles (Pub. Pearson Education, Singapore) Vol.1. [10] Wiberg, K.B. and Connon, H.A. (1976).Isolation and synthesis of PinoresinolDiglucoside, a major anti-hypertensive [4] Jack, I.R. (1981) Ph.D. Thesis submitted to the University of principle of Tu-ching. Journal of the American Chemical Wales. Society 98 (17), 5412-5413. [5] Jack, I.R. and Okorosaye-Orubite, K. (2009).Some constituents of the bark of Gmelinaarborea .Scientia Africana, 8(1), 26-32.