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Volume 68 
Part 4 
Pages m94-m96  
April 2012  

Received 31 January 2012
Accepted 8 March 2012
Online 14 March 2012

Absolute configuration of strictosidinic acid

aInstituto de Física - UFG, Caixa Postal 131, 74001-970 Goiânia, GO, Brazil, and bInstituto de Química - UFG, Caixa Postal 131, 74001-970 Goiânia, GO, Brazil
Correspondence e-mail: jrsabino@if.ufg.br

The absolute configuration of strictosidinic acid, (2S,3R,4S)-3-ethenyl-2-([beta]-D-glucopyranosyloxy)-4-{[(1S)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl]methyl}-3,4-dihydro-2H-pyran-5-carboxylate, was determined from its sodium chloride trihydrate, poly[[diaqua((2S,3R,4S)-3-ethenyl-2-([beta]-D-glucopyranosyloxy)-4-{[(1S)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-2-ium-1-yl]methyl}-3,4-dihydro-2H-pyran-5-carboxylate)sodium] chloride monohydrate], {[Na(C26H32N2O9)(H2O)2]Cl·H2O}n. The strictosidinic acid molecule participates in intermolecular hydrogen bonds of the O-H...O and O-H...Cl types. The solid-state conformation was observed as a zwitterion, based on a charged pyridine N atom and a carboxylate group, the latter mediating the packing through coordination with the sodium cation.

Comment

Palicourea coriacea (Rubiaceae), popularly known as Douradinha, is a typical plant of the Brazilian savanna (Cerrado), whose tea is popularly used in folk medicine for the treatment of kidney stones and kidney and urethra inflammation, as well as having an effective diuretic action. Previous studies of this genus have yielded triterpenes (Bolzani et al., 1992[Bolzani, V. S., Trevisan, L. M. V. & Young, M. C. M. (1992). Rev. Latinoam. Quim. 23, 20-21.]), alkaloids (do Nascimento et al., 2006[Nascimento, C. A. do, Gomes, M. S., Lião, L. M., de Oliveira, C. M. A., Kato, L., de Silva, C. C. & Tanaka, C. M. A. (2006). Z. Naturforsch. Teil B, 61, 1443-1446.]), fluoroacetate (Kemmerling, 1996[Kemmerling, W. (1996). Z. Naturforsch. Teil C, 51, 59-64.]), coumarins (El-Seedi, 1999[El-Seedi, H. R. (1999). Rev. Latinoam. Quim. 27, 13-16.]) and macrocyclic peptides (Bokesch et al., 2001[Bokesch, H. R., Pannell, L. K., Cochran, P. K., Sowder, R. C. II, McKee, T. C. & Boyd, M. R. (2001). J. Nat. Prod. 64, 249-250.]), many of them possessing interesting biological properties, such as anti-HIV (Bokesch et al., 2001[Bokesch, H. R., Pannell, L. K., Cochran, P. K., Sowder, R. C. II, McKee, T. C. & Boyd, M. R. (2001). J. Nat. Prod. 64, 249-250.]) and anticancer activities (Hartwell, 1971[Hartwell, J. L. (1971). Lloydia, 34, 204-255.]). As part of our continued interest in plants from the Brazilian Cerrado (Lião et al., 2001[Lião, L. M., Silva, M. V., Costa, T. R., Costa, M. R., Ferreira, E. C., Fernandes, O. F. L., Santos, S. C., Ferri, P. H., Paula, J. R., Ferreira, H. D. & Silva, M. R. R. (2001). Pharm. Biol. 39, 138-141.]), we have investigated the leaves of P. coriacea. Strictosidinic acid, an alkaloid that has important biological properties, was isolated and its structure has been elucidated based on NMR and IR spectroscopic data, and its absolute structure was determined by X-ray crystallographic analysis.

The strictosidinic acid molecule is composed of a tryptoline moiety bonded to a pyran ring bonded to a [beta]-glucose group. This molecule crystallized as a sodium chloride trihydrate, (I)[link], with three water molecules, a coordinated sodium cation and a chloride counter-ion. The indole group of the tryptoline moiety shares a double bond [C2=C10 = 1.371 (6) Å] with the six-membered heterocyclic pyridinium ring (N13/C1/C2/C10/C11/C12), which adopts a half-chair conformation with the protonated N13 atom as the flap atom [puckering parameters: Q = 0.513 (4) Å, [theta] = 49.7 (5)° and [varphi] = 349.6 (7)°; Cremer & Pople, 1975[Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354-1358.]; Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]]. The pyran ring (C20/C19/O18/C17/C16/C15) includes a C=C double bond [C16=C17 = 1.341 (6) Å] which allows for a half-chair conformation with C20 as the flap atom [puckering parameters: Q = 0.501 (5) Å, [theta] = 125.1 (5)° and [varphi] = 198.6 (6)°]. This pyran ring is substituted with a carboxylate group (C21/O22/O23) in the 5-position (on C16), which is coordinated to the sodium cation through the O22 carbonyl group. Atom O23 transfers its proton to amine atom N13 and is a strong hydrogen-bond acceptor from both N13 and the O1S water molecule (Table 1[link]), which is also coordinated to the sodium cation. The C21=O22 bond is lengthened to 1.248 (5) Å and C21-O23 is shortened to 1.274 (5) Å, indicating that electron delocalization increases in this group. Given that the C15-C16-C21-O23 torsion angle is 9.8 (6)°, there is no resonance between the carboxylate group and the pyran ring C=C double bond, which is reflected in the elongation of the C16-C21 single bond to 1.501 (6) Å, compared with the expected formal bond distance. The N13-C1 and N13-C12 single bonds of 1.509 (6) and 1.501 (6) Å, respectively, indicate that the N13 atom is sp3-hybridized. The [beta]-glucose group shows a chair conformation [puckering parameters: Q = 0.574 (5) Å, [theta] = 6.0 (5)° and [varphi] = 300 (4)°], with O32 as the pivot atom.

[Scheme 1]

A search of the Cambridge Structural Database (CSD, Version 5.23, May 2011 update; Allen, 2002[Allen, F. H. (2002). Acta Cryst. B58, 380-388.]) gave two structures with a chiral tryptoline moiety not substituted in the C12 and N13 positions, namely 1(S)-([alpha]-D-arabinofuranosyl)-1,2,3,4-tetrahydro-[beta]-carboline (CSD refcode DOJBIN; Piper et al., 1985[Piper, I. M., MacLean, D. B., Faggiani, R., Lock, C. J. L. & Szarek, W. A. (1985). Can. J. Chem. 63, 2915-2921.]) and 1-[2-(pyrrolidin-1-yl)phenyl]-2,3,4,9-tetrahydro-1H-[beta]-carboline (HOPNOQ; Zhang et al., 2009[Zhang, C., Murarka, S. & Seidel, D. (2009). J. Org. Chem. 74, 419-422.]). In general, the bond lengths are comparable within standard uncertainty, the exceptions (see Table 1[link]) being N3-C2 which is shorter in (I)[link] by 0.036 Å compared to DOJBIN, N13-C1 which is longer in (I)[link] by 0.032 and 0.026 Å, respectively, compared to DOJBIN and HOPNOQ, and N13-C12 which is longer in (I)[link] by 0.03 Å compared to HOPNOQ. These elongated N13-C bonds might be ascribed to the lowered charge density in these bonds due to the quaternary N atom.

Because the natural extract contained salt, this allowed the establishment of the absolute configuration of (I)[link] (Flack & Bernardinelli, 1999[Flack, H. D. & Bernardinelli, G. (1999). Acta Cryst. A55, 908-915.], 2000[Flack, H. D. & Bernardinelli, G. (2000). J. Appl. Cryst. 33, 1143-1148.]); we determined the chiral centers as follows: C1 S, C15 S, C19 S, C20 R, C27 S, C28 R, C29 S, C30 R and C31 R.

The sodium cation is involved in the packing stabilization mediating the intermolecular interactions, being five-coordinated by the hydroxy O34vi atom, the methoxy O37v atom, the carboxylate O22 atom and the O1S and O2S water molecules (symmetry codes as in Fig. 1[link]). In the crystal, there are classical intermolecular interactions (a) where the strictosidinic acid molecule acts as a donor (O33-H33...O22i) and (b) involving the coordinated O2S water molecule (O2S-H2SB...O35i). There are also nonclassical intermolecular hydrogen-bond interactions, viz. O34-H34...Cl1, O35-H35...Cl1 and O37-H37...Cl1iv (Table 2[link]). The O3S water molecule is involved in intermolecular interactions both as a donor, viz. in O3S-H3SA...O1S and O3S-H3SB...O26iii, and as an acceptor, viz. in O2S-H2SA...O3Sii (symmetry codes as in Table 2[link]). All these intermolecular interactions create a three-dimensional polymeric chain.

[Figure 1]
Figure 1
The molecular structure of (I)[link], showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level. Dashed lines indicate intramolecular interactions. [Symmetry codes: (i) x + [{1\over 2}], -y + [{3\over 2}], -z + 1; (v) x - [{1\over 2}], -y + [{3\over 2}], -z + 1; (vi) -x + [{1\over 2}], -y + 2, z - [{1\over 2}]; (vii) -x + [{1\over 2}], -y + 2, z + [{1\over 2}].]

Experimental

The air-dried and powdered leaves (362 g) of P. coriacea were successively extracted with EtOH (1.5 l for 48 h). The resulting extract was filtered and concentrated under reduced pressure to give 41.3 g of residue to which was added a 10% HOAc solution (250 ml) and the suspension was kept at 278 K overnight. The suspension was filtered and the acidic aqueous phase was partitioned with CH2Cl2. The resulting aqueous layer was basified (pH 8-9) with saturated NaHCO3 solution, and was then extracted with CH2Cl2. The combined organic layers were treated with Na2SO4 and filtered, affording a CH2Cl2 basic fraction. Strictosidinic acid (29 mg) was obtained from a crude methanolic extract of the leaves after repeated fractionation using column chromatography (CHCl3/MeOH gradient eluent system) followed by preparative thin-layer chromatography on silica gel (organic phase: n-butanol/HOAc/H2O 4:1:5 v/v/v). Crystals suitable for single-crystal X-ray diffraction studies were obtained as yellow blocks by recrystallization from chloroform and methanol (1:1 v/v) (m.p. 482-485 K).

Crystal data
  • [Na(C26H32N2O9)(H2O)2]Cl·H2O

  • Mr = 629.02

  • Orthorhombic, P 21 21 21

  • a = 7.6419 (4) Å

  • b = 16.2205 (8) Å

  • c = 23.4299 (12) Å

  • V = 2904.3 (3) Å3

  • Z = 4

  • Cu K[alpha] radiation

  • [mu] = 1.89 mm-1

  • T = 100 K

  • 0.2 × 0.15 × 0.1 mm

Data collection
  • Bruker SMART APEX DUO diffractometer

  • Absorption correction: multi-scan (SADABS; Bruker, 2001[Bruker (2001). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.706, Tmax = 0.835

  • 22917 measured reflections

  • 5062 independent reflections

  • 4390 reflections with I > 2[sigma](I)

  • Rint = 0.078

Refinement
  • R[F2 > 2[sigma](F2)] = 0.063

  • wR(F2) = 0.159

  • S = 1.14

  • 5062 reflections

  • 402 parameters

  • 6 restraints

  • H atoms treated by a mixture of independent and constrained refinement

  • [Delta][rho]max = 0.53 e Å-3

  • [Delta][rho]min = -0.26 e Å-3

  • Absolute structure: Flack (1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]), 2134 Friedel pairs

  • Flack parameter: 0.04 (3)

Table 2
Hydrogen-bond geometry (Å, °)

D-H...A D-H H...A D...A D-H...A
O1S-H1SB...Cl1i 0.84 (2) 2.35 (2) 3.192 (4) 177 (6)
O1S-H1SA...O23 0.85 (2) 1.85 (2) 2.694 (5) 176 (7)
O2S-H2SA...O3Sii 0.84 (2) 1.90 (3) 2.726 (6) 165 (7)
O2S-H2SB...O35i 0.83 (2) 2.00 (3) 2.816 (5) 167 (6)
O3S-H3SA...O1S 0.85 (2) 2.33 (8) 2.801 (6) 115 (7)
O3S-H3SB...O26iii 0.85 (2) 2.50 (4) 3.276 (5) 152 (7)
O33-H33...O22i 0.84 1.95 2.711 (4) 151
O34-H34...Cl1 0.84 2.42 3.217 (3) 158
O35-H35...Cl1 0.84 2.30 3.134 (3) 172
O37-H37...Cl1iv 0.84 2.43 3.209 (4) 154
N3-H3...Cl1iv 0.88 2.44 3.314 (4) 173
N13-H13B...O23 0.92 1.69 2.576 (5) 160
Symmetry codes: (i) [x+{\script{1\over 2}}, -y+{\script{3\over 2}}, -z+1]; (ii) [-x+1, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]; (iii) [-x+{\script{3\over 2}}], [-y+2, z-{\script{1\over 2}}]; (iv) [-x+1, y+{\script{1\over 2}}, -z+{\script{3\over 2}}].

Table 1
Exceptional tryptoline moiety bond lengths (Å)

Bond (I) DOJBIN HOPNOQ
N3-C2 1.353 (6) 1.389 (4) 1.374 (3)
N13-C1 1.509 (6) 1.477 (4) 1.483 (3)
N13-C12 1.501 (6) 1.487 (5) 1.471 (3)
CSD refcodes: DOJBIN (Piper et al., 1985[Piper, I. M., MacLean, D. B., Faggiani, R., Lock, C. J. L. & Szarek, W. A. (1985). Can. J. Chem. 63, 2915-2921.]) and HOPNOQ (Zhang et al., 2009[Zhang, C., Murarka, S. & Seidel, D. (2009). J. Org. Chem. 74, 419-422.]).

All water H atoms were located in a difference Fourier map, and refined with restraints on bond distances using O-H = 0.84 (2) Å. The remaining H atoms were positioned geometrically (aromatic C-H = 0.95 Å, methine C-H = 1.00 Å, alkyl C-H = 0.99 Å, ethylene C-H = 0.95 Å, N+-H = 0.92 Å, aromatic N-H = 0.88 Å and hydroxy O-H = 0.84 Å) and refined using a riding model, with Uiso(H) = 1.2Ueq(C, N, Owater) and 1.5Ueq(Ohydroxy). Hydroxy groups were allowed to rotate in order to fit the difference electron-density map.

Data collection: APEX2 (Bruker, 2007[Bruker (2007). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2007[Bruker (2007). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997[Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.]); software used to prepare material for publication: WinGX (Farrugia, 1999[Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837-838.]).


Supplementary data for this paper are available from the IUCr electronic archives (Reference: LG3078 ). Services for accessing these data are described at the back of the journal.


Acknowledgements

The authors acknowledge the financial support of CNPq and FUNAPE/UFG. JRS is grateful to Holger Ott (Bruker AXS at Karlsruhe) for the data collection during a demonstration visit.

References

Allen, F. H. (2002). Acta Cryst. B58, 380-388.  [ISI] [CrossRef] [details]
Bokesch, H. R., Pannell, L. K., Cochran, P. K., Sowder, R. C. II, McKee, T. C. & Boyd, M. R. (2001). J. Nat. Prod. 64, 249-250.  [ISI] [CrossRef] [PubMed] [ChemPort]
Bolzani, V. S., Trevisan, L. M. V. & Young, M. C. M. (1992). Rev. Latinoam. Quim. 23, 20-21.  [ChemPort]
Bruker (2001). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.
Bruker (2007). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.
Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354-1358.  [CrossRef] [ChemPort] [ISI]
El-Seedi, H. R. (1999). Rev. Latinoam. Quim. 27, 13-16.  [ChemPort]
Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.  [CrossRef] [details]
Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837-838.  [CrossRef] [ChemPort] [details]
Flack, H. D. (1983). Acta Cryst. A39, 876-881.  [CrossRef] [details]
Flack, H. D. & Bernardinelli, G. (1999). Acta Cryst. A55, 908-915.  [CrossRef] [details]
Flack, H. D. & Bernardinelli, G. (2000). J. Appl. Cryst. 33, 1143-1148.  [ISI] [CrossRef] [ChemPort] [details]
Hartwell, J. L. (1971). Lloydia, 34, 204-255.  [ChemPort] [PubMed]
Kemmerling, W. (1996). Z. Naturforsch. Teil C, 51, 59-64.  [ChemPort]
Lião, L. M., Silva, M. V., Costa, T. R., Costa, M. R., Ferreira, E. C., Fernandes, O. F. L., Santos, S. C., Ferri, P. H., Paula, J. R., Ferreira, H. D. & Silva, M. R. R. (2001). Pharm. Biol. 39, 138-141.
Nascimento, C. A. do, Gomes, M. S., Lião, L. M., de Oliveira, C. M. A., Kato, L., de Silva, C. C. & Tanaka, C. M. A. (2006). Z. Naturforsch. Teil B, 61, 1443-1446.
Piper, I. M., MacLean, D. B., Faggiani, R., Lock, C. J. L. & Szarek, W. A. (1985). Can. J. Chem. 63, 2915-2921.  [CrossRef] [ChemPort] [ISI]
Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.  [CrossRef] [details]
Spek, A. L. (2009). Acta Cryst. D65, 148-155.  [ISI] [CrossRef] [details]
Zhang, C., Murarka, S. & Seidel, D. (2009). J. Org. Chem. 74, 419-422.  [CSD] [CrossRef] [PubMed] [ChemPort]


Acta Cryst (2012). C68, m94-m96   [ doi:10.1107/S0108270112010372 ]