Cryst Res Technol 37 2002 627–633 P LUGER1*, M WEBER1, N X DUNG2, V T LUU3, D D RANG3, D T TUONG3, P H NGOC3 Institut für Chemie/Kristallographie, Freie Universität Berlin, Germany Center for Education and Development of Chromatography of Vietnam and Hanoi University of Natural Sciences Hanoi Teacher's Training College and NCST of Vietnam The Crystal Structure of 3-(4'-Methoxyphenyl)propanoyl pyrrole of Piper lolot C.DC from Vietnam C14H15NO2 (293K): monoclinic space group P21/n, a = 24.580(10), b = 5.536(2), c = 9.037(3) Å, β= 91.18(4)°, V = 1229.4(8) Å3, Dx = 1.239 g⋅cm-3, Z = 4, F(000) = 488, λ(CuKα) = 1.5418 Å, µ= 0.667 mm-1 The title compound which was isolated from the rhizomes of Piper lolot C.DC has antibacterial activity Its chemical identity was established by this X-ray analysis The molecule consists of a planar propanoyl pyrrole and a methoxyphenyl fragment with an interplanar angle of 93.8(3)° which is by 30° larger than the corresponding angle reported in the literature for the comparable dimethoxy derivative, which was also derived from Piper species Keywords: crystal structure, piper lolot (Received March 6, 2002; Accepted April 22, 2002) Introduction Pharmaceutically active compounds from domestic plants play an important role in the traditional folk medicinal system in East Asia Although the knowledge about the medicinal activity is generally based on long oral tradition from generation to generation, in several cases the chemical identity of the extracted compounds was not known, being now a challenging task for modern analytical methods The title compound was isolated from the rhizomes of Piper lolot C.DC by extraction with n-hexane Piper lolot C.DC is known for its activity against the bacteria Bacillus pyocyaneus, Staphyloccocus aureus and B subtilis with simultanous anti-inflamatory action It is also in use to treat various deseases like rheumatism, lumbago, digestive troubles, vomiting, diarrhoea and others (LOI, 1995; TRUYEN & CHAU, 1999) The genus Piper belong to the Piperaceae and has over 700 species distributed in both hemispheres The Piper species have high commercial, economical and medicinal importance Piper lolot C.DC is one species of genus Piper and reputed for its medicinal properties in folklore medicine of Vietnam The chemistry of Piper lolot C.DC has been investigated only on essential oil The essential oil isolated by hydro-distillation from the fresh leaves, stem and rhizomes of Piper lolot C.DC has been analyzed for the first time by a combination of GC and GC/MS The oils contained more than 35 compounds, of which 25 constitutes could be identified according to * corresponding author: luger@chemie.fu-berlin.de © WILEY-VCH Verlag Berlin GmbH, 13086 Berlin, 2002 0232-1300/02/0606-0627 $ 17.50+.50/0 628 P LUGER et al.: Crystal Structure their chromatographic retension indices and mass spectra (DUNG, THANH, KHOI, LECLERCQ, 1996) The lack of phytochemical investigation of the Piper lolot C.DC extract led us to this study From n-hexane extract of the rhizome of the Piper lolot C.DC, we separated two compounds by column chromatography, one of them is β-asarone (RANG, TUONG & LUU, 2001) and the other one is this compound with MW = 229, mp 81-82°C Since its chemical indentity was originally not known, its structure was elucidated by X-ray analysis Table 1: Crystal data, details of data collection and structure determination Formula Mr a (Å) b (Å) c (Å) β (°) V (Å3) Z Space group Dx (Mg⋅m-3) F(000) Radiation [λ (Å)] µ (mm-1) Crystal size (mm) Diffractometer No of reflections measured No of independent reflections hmin, hmax kmin, kmax lmin, lmax θmax (°) Rint Refinement (on 2146 reflections) No of parameters refined No of reflections [Fo > 2σ(Fo)] wR(F2) (overall) wR(F2) (obs) R (overall) R (obs) Mean shift/esd Difference electron density (eÅ-3) maximum Difference electron density (eÅ-3) minimum C14 H15 NO2 229.27 24.580(10) 5.536(2) 9.037(3) 91.18(4) 1229.4(8) P21/n 1.239 488 CuKα(1.5418) 0.667 0.46 x 0.42 x 0.11 STOE 4-circle 2312 2146 -29, 29 0, 0, 10 65.99 0.02 F2 215 1929 0.104 0.099 0.0426 0.0377 0.06 0.15 -0.14 *CCDC 179879 contains the supplementary crystallographic data for this paper These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033; or deposit@ccdc.cam.ac.uk) Cryst Res Technol 37 (2002) 629 Experimental Rhizomes of Piper lolot C.DC were collected in a garden of Hanoi, Vietnam A voucher specimen has been deposited in the Herbarium of the Institute of Ecology and Biological Resources, NCST, Hanoi, Vietnam Rhizome of Piper lolot C.DC was washed with destilled water and dried at 60-70°C until dryness and pulverized Rhizome-powder of Piper lolot was extracted by n-hexane at room temperature in 10 days After filtration the n-hexane extract was evaporated to dryness under reduced pressure The mixture was chromatographied on a silicagel-column, elution was started with a mixture of n-hexane-ethylacetate with increasing polarity (from 0% to 100% ethylacetate) Pure compound was collected after re-column chromatography yielding plate shaped crystals, melting point 81-82°C, MS(m/z), MW = 229, IR cm-1 (KBr) 3153 (=NH), 31003000 (=CH-), 2938 ( > CH2), 2810 (-OCH3), 1715 ( > C=O), 1514-1480 (aromatic ring), 1245 (C-O) Fig 1: ORTEP representation (JOHNSON, 1976) of the molecular structure and atom numbering scheme of the title compound, the thermal ellipsoids are drawn at a probability of 50% A crystal with dimensions 0.46 x 0.41 x 0.11 mm was used for all X-ray investigations, which were carried out on a STOE four circle diffractometer using Ni-filtered CuKα radiation Crystal data and details of the intensity data collection are summarized in Table The unit cell constants were determined by least-squares refinement of 43 reflections in a range 30° < 2θ < 90° The repeated measurement of three standard reflections (frequency: 90 minutes) revealed no significant decay (maximum intensity variation 3%) during the data 630 P LUGER et al.: Crystal Structure collection The intensity data were corrected for Lorentz and polarization factors, but not for absorption The atomic scattering factors were taken from International Tables for X-ray Crystallography, Vol C The phase problem was solved by routine application of direct methods (program SHELXS, SHELDRICK, 1986), least-squares refinements with anisotropic displacement parameters for C, N and O and isotropic displacement parameters for H (calculated from stereochemical considerations and allowed for free refinement), including an isotropic extinction parameter, were executed using SHELXL97 (SHELDRICK, 1997) Details of the refinement are included in Table 1, final atomic parameters are in Table 2, geometric parameters are in Table Table 2: Fractional atomic coordinates and equivalent isotropic displacement parameters (Å2) U eq = (1 3) ∑ i ∑ j U ij ai* a*j ⋅ a j C1 C2 C3 C4 O4 C41 C5 C6 C7 C8 C9 O9 N10 C11 C12 C13 C14 x 1194(1) 1654(1) 2047(1) 1997(1) 2418(1) 2380(1) 1542(1) 1147(1) 768(1) 326(1) -114(1) -94(1) -573(1) -1035(1) -1387(1) -1148(1) -655(1) y -2889(3) -3114(3) -4806(3) -6347(2) -7932(2) -9616(3) -6188(3) -4472(3) -1003(3) -1914(3) -91(2) 1963(2) -861(2) 535(3) -742(3) -2997(4) -3054(3) z 9019(2) 8163(2) 8467(2 9662(1) 9889(1) 11062(2) 10534(2) 10196(2) 8671(2) 7620(2) 7328(2) 7772(2) 6511(1) 6244(2) 5406(2) 5127(2) 5813(2) Ueq 54(1) 60(1) 60(1) 50(1) 67(1) 70(1) 56(1) 59(1) 65(1) 60(1) 53(1) 79(1) 53(1) 62(1) 68(1) 78(1) 69(1) Table 3: Selected bond lengths (Å), angles (°) and torsion angles (°) C1-C7 C4-O4 O4-C41 C7-C8 C8-C9 C9-O9 C9-N10 N10-C14 N10-C11 C11-C12 C12-C13 1.508(2) 1.370(2) 1.416(2) 1.514(2) 1.498(2) 1.207(2) 1.402(2) 1.381(2) 1.391(2) 1.340(2) 1.405(3) Cryst Res Technol 37 (2002) C13-C14 O4-C4-C3 O4-C4-C5 C4-O4-C41 O9-C9-N10 O9-C9-C8 N10-C9-C8 C14-N10-C11 C14-N10-C9 C11-N10-C9 C12-C11-N10 C11-C12-C13 C14-C13-C12 C13-C14-N10 C3-C4-O4-C41 C6-C1-C7-C8 C2-C1-C7-C8 C1-C7-C8-C9 C7-C8-C9-O9 C7-C8-C9-N10 O9-C9-N10-C14 C8-C9-N10-C14 O9-C9-N10-C11 631 1.348(2) 115.6(1) 124.9(1) 118.2(1) 119.2(1) 123.5(1) 117.2(1) 107.3(1) 128.1(1) 124.6(1) 108.7(2) 107.6(2) 108.3(2) 108.2(2) -177.7(1) -89.8(2) 90.2(2) 177.1(1) 6.5(2) -172.6(1) 174.5(2) -6.4(2) -4.6(2) Results and Discussion The molecular structure of the title compound is shown in Fig along with the atomic numbering scheme The molecule consists of two almost planar structural fragments, a propanoyl pyrrole and a methoxyphenyl unit The average deviations of contribution (non H) atoms to least squares planes are 0.06 Å for the first plane and 0.009 Å for the latter one The interplanar angle is 93.8(3)°, hence the two fragments are almost perpendicular to each other A very similar molecule, also from a Piper species (Piper brachystachyum), is reported in the literature (KUMAR et al., 1998) 1-[3-(3,4-dimethoxyphenyl)propanoyl]pyrrole differs from the title compound only by a further methoxy group in meta position of the phenyl ring The graphical superposition (Fig 2) shows that both molecules differ by the dihedral angle of the two major molecular planes which is 64.2(1)°, hence smaller for the dimethoxy derivative Otherwise the geometry of the two molecules is rather alike, e.g the linear chain is in an all trans arrangement, the methoxy group(s) is(are) in plane with the phenyl ring Bond lengths and angles are as expected and need no detailed discussion Especially the values in the amide group and the double bonds in the pyrrole ring are in line with the dimethoxy derivative and a number of benzoyl and toluoyl substituted pyrrole derivatives (BENNET, SOMAYAJI, BROWN & SANTARSIERO, 1991; BEACH, BATCHELOR, EINSTEIN & BENNET, 1998) In the crystal lattice (see Fig 3) the molecules are in head-to-tail arrangements forming r r infinite chains in the a + c direction Neighboured molecules in a chain are connected by 632 P LUGER et al.: Crystal Structure the shortest intermolecular contact in this structure being a C-H O link from C12-H12 of the pyrrole ring to the methoxy O4 of a glide plane related molecule, with H O = 2.70(4)Å A second C-H O contact is C8-H82 to the carbonyl O9 of a molecule related by a translation r in b -direction (H O = 2.71(4)Å) Further close intermolecular contacts are not observed Fig 2: Graphical superposition of the title molecule (solid lines) and 1-(3-(3,4-dimethoxyphenyl)propanoyl)pyrrole (filled dashed lines), generated with SCHAKAL (KELLER, 1988) r r Fig 3: Illustration of the crystal packing in a projection on the a — c -plane H12 O4 (dashed line) is the shortest intermolecular contact (SCHAKAL drawing, KELLER, 1988) References BEACH, L J., BATCHELOR, R J., EINSTEIN, F W B., BENNET, A J.: Can J Chem 76 (1998) 1410-1418 BENNET, A J., SOMAYAJI, V., BROWN, R S., SANTARSIERO, B D.: J Am Chem Soc 113 (1991) 75637571 Cryst Res Technol 37 (2002) 633 DUNG, N X., THANH, L., KHOI, T T., LECLERCQ, P A.: J Essent Oil Res (1996) 649-652 International Tables for X-Ray Crystallography Vol C (1992): Kluwer Academic Publishers JOHNSON, C K (1976) ORTEP II, Report ORNL-5138, Oak Ridge National Laboratory, Tennessee, USA KELLER, E: SCHAKAL88 A Fortran Program for the Graphical Representation of Molecular and Crystallographic Models Univ Freiburg, Germany (1988) KUMAR, R., PARMER, V S., ERRINGTON, W., WENGEL, J., OLSEN, C E.: Acta Cryst C54 (1998) 233365 LOI, D T.: Cac cay thuoc va vi thuoc Viet Nam Sci and Tech Pub House (1995) RANG, D D., TUONG, D T., LUU, V T.: Chem and Chem Industry (in Vietnamese) (2001) 25-29 SHELDRICK, G M (1985): SHELXS-86 Crystallographic Computing 3, edited by G M Sheldrick, C Krüger, R Goddard, pp 175-189, Oxford University press SHELDRICK, G M.: SHELXL-97 (1997), A FORTRAN-77 Program for Refinement of Crystal Structures, Universität Göttingen, Germany TRUYEN, L V., CHAU, N G (Editors): Selected Medicinal Plants in Vietnam, Science and Technology Publishing House Hanoi (1999) 182-184 ... this study From n-hexane extract of the rhizome of the Piper lolot C.DC, we separated two compounds by column chromatography, one of them is β-asarone (RANG, TUONG & LUU, 2001) and the other one... LUGER et al.: Crystal Structure their chromatographic retension indices and mass spectra (DUNG, THANH, KHOI, LECLERCQ, 1996) The lack of phytochemical investigation of the Piper lolot C.DC extract... Rhizomes of Piper lolot C.DC were collected in a garden of Hanoi, Vietnam A voucher specimen has been deposited in the Herbarium of the Institute of Ecology and Biological Resources, NCST, Hanoi, Vietnam