Crystallography Reports, Vol. 46, No. 2, 2001, pp. 230–234. From Kristallografiya, Vol. 46, No. 2, 2001, pp. 271–275.Original English Text Copyright © 2001 by Rajnikant, Gupta, Lal.

STRUCTURE OF ORGANIC COMPOUNDS

Crystallographic Analysis of Royline Monohydrate [C25H41NO7 · H2O]*

Rajnikant**, V. K. Gupta, and M. LalX-ray Crystallography Laboratory, Postgraduate Department of Physics,

University of Jammu, Jammu Tawi, 180 006 IndiaReceived September 8, 1999; in final form, April 17, 2000

Abstract—The crystal and molecular structures of the alkaloid Royline {(1α,6β,14α,16β)-20-ethyl-4-hydroxymethyl)-1,6,14,16-tetramethoxyaconitane-7,8-diol} with a water molecule has been determined byX-ray diffraction analysis. The compound crystallizes in the space group P21 with the unit cell parameters a =10.985(1) Å, b = 7.898(1) Å, c = 14.956(1) Å, β = 102.96(1)°, V = 1264.52 Å3, Z = 2, λMoKα = 0.71073 Å,and R = 0.033 for 2067 observed reflections. Rings A, B, and C adopt a chair conformation, ring D is a half-boat, ring E is a half-chair, and ring F is in an envelope conformation with C(14) at the flap. Molecules arelinked together in the crystal by hydrogen bonds. © 2001 MAIK “Nauka/Interperiodica”.

INTRODUCTION

The title compound is a diterpenoid alkaloid iso-lated from Inula royleana, a shrub growing on the west-ern temperate Himalayas at an altitude of 7000–12000 ft above the sea level. The plant is considered tobe poisonous and is used as a disinfectant and as aninsectiside. It is known to be commonly used againstthe head louse [1]. The chemical structure as assignedto this compound on the basis of its IR, UV, NMR, andmass spectral data is shown in Fig. 1 [2].

EXPERIMENTAL

Transparent single crystals of Royline in the form ofplates were grown from methanol by the slow evapora-tion technique at room temperature. Three-dimensionalintensity data were collected on an Enraf–NoniusCAD4 diffractometer (MoKα radiation). The unit cellparameters were refined by the least-squares procedure.Data were corrected for Lorentz and polarization fac-tors, but no absorption or extinction corrections weremade.

The structure was solved by direct methods usingthe SHELXS86 software package [3] and refined byusing the SHELXL93 software package [4]. A total of43 hydrogen atoms were used in the structure determi-nation, of which 25 hydrogen atoms were located fromthe difference Fourier map, and their positions and iso-tropic temperature factors were refined. The remaining18 hydrogen atoms were placed in geometrically calcu-lated positions, and their coordinates were refined inthe structure factor calculations. The final refinementcycle converged to R = 0.033, wR(F2) = 0.087, and S =

* This article was submitted by the authors in English.** Author for correspondence.

1063-7745/01/4602- $21.00 © 200230

1.176. Atomic scattering factors were taken from theInternational Tables for X-ray Crystallography (1992,Vol. C, Tables 4.2.6.8 and 6.1.1.4). The crystallo-graphic data are summarized in Table 1.

RESULTS AND DISCUSSION

The fractional coordinates and equivalent isotropictemperature factors for non-hydrogen atoms are pre-sented in Table 2. Endocyclic torsion angles for differ-ent rings of the molecule are listed in Table 3. A generalview of the molecule with atomic labeling is shown inFig. 2 [5].

The geometric parameters of the molecule, that is,bond lengths and bond angles, are quite close to thoseof some analogous structures [6–8]. The central ringsystem of Royline is formed by the fusion of four six-membered and two five-membered rings. The meanvalue of three C(sp3)–N bonds [1.465(11) Å] is compa-rable with the corresponding values obtained in thecase of Delvestine [6] and Delsoline [7].

CH3O

OH

H3C

OCH3

OCH3

OHOH

H3CO

N

Fig. 1. Chemical structure of Royline.

01 MAIK “Nauka/Interperiodica”

CRYSTALLOGRAPHIC ANALYSIS OF ROYLINE MONOHYDRATE 231

Table 1. Crystal data and other experimental details

Crystal habit White transparent plate

Chemical formula C25H41NO7 · H2O

Molecular weight 485.65

Unit cell parameters a = 10.985(1) Å, b = 7.898(1) Åc = 14.956(1) Å, β = 102.96(1)°

Unit cell volume 1264.52 Å3

Crystal system Monoclinic

Space group P21

Density dcalcd 1.275 g/cm3

No. of molecules per unit cell (Z) 2

Radiation MoKα

Wavelength (λ) 0.71073 Å

Absorption coefficient (µ) 0.09 mm–1

F(000) 528

Crystal size 0.30 × 0.22 × 0.12 mm

Refinement of unit cell 25 reflections, (8.1° < θ < 13.9°)

θ range for the entire data collection 2° < θ < 25°

No. of measured reflections 2399

No. of unique reflections 2264

No. of observed reflections 2067

No. of parameters refined 462

Final R-factor 0.033

wR 0.087

Weighting scheme 1/[σ2( ) + (0.0472P)2 + 0.16P], where P = [ + 2 ]/3

Final residual electron density –0.12 < ∆ρ < 0.20 eÅ–3

(∆/σ)max in the final cycle 0.809, where z H(241)

Flack parameter X 0.65

F02

F02

F02

Ring A [C(1)C(2)C(3)C(4)C(5)C(11)] exists in adistorted chair conformation with the C(2) and C(5)atoms lying above and below the plane of the remainingfour atoms [the deviation is 0.583(3) Å for C(2) and−0.675(3) Å for C(5)]. Ring B [C(4)C(5)C(11) C(17)NC(19)] adopts a distorted chair conformation withC(5) [−0.815(3) Å] and N [0.540(2) Å] atoms lying belowand above the plane. Ring C [C(7)C(8) C(9)C(10)C(11)C(17)] also takes the shape of a distorted chair

CRYSTALLOGRAPHY REPORTS Vol. 46 No. 2 2001

with the C(11) atom lying below [–0.718(2) Å] and theC(8) atom lying above [0.652(2) Å] the plane. Ring D[C(8)C(9)C(14)C(13)C(16)C(15)] adopts a half-boatconformation with the C(14) and C(15) atoms deviat-ing below the plane by –0.853(3) and –0.213(3) Å,respectively. The five-membered ring E [C(5)C(6)C(7)C(17)C(11)] acquires a half-chair conformation withthe asymmetry parameter ∆C2[C(11)–C(17)] = 3.9 andthe pseudorotation parameters ∆ = 5.5° and φ = 53.4° [9].

232

RAJNIKANT

et al

.

Table 2. Atomic coordinates and equivalent isotropic thermal parameters (Å2)

Atom x y z

Ow 1.1562(3) 0.2405(4) 1.1106(2) 0.0762(10)

O(1) 1.0877(2) 0.5436(3) 0.5842(1) 0.0607(7)

O(6) 1.3822(2) 0.3215(3) 0.9440(1) 0.0473(6)

O(7) 1.3359(2) 0.0201(2) 0.7870(1) 0.0429(6)

O(8) 1.2220(2) 0.0689(3) 0.9293(1) 0.0438(6)

O(14) 0.9719(2) 0.2065(3) 0.9405(1) 0.0465(6)

O(16) 0.8525(2) –0.0040(3) 0.7576(2) 0.0618(8)

O(18) 1.5962(2) 0.6612(3) 0.8463(2) 0.0732(9)

N 1.3283(2) 0.2598(3) 0.6407(1) 0.0395(7)

C(1) 1.1966(3) 0.5876(3) 0.6525(2) 0.0392(9)

C(2) 1.3012(3) 0.6285(4) 0.6049(2) 0.0459(9)

C(3) 1.4242(3) 0.6500(4) 0.6731(2) 0.0491(11)

C(4) 1.4544(2) 0.4943(4) 0.7348(2) 0.0430(9)

C(5) 1.3554(2) 0.4749(3) 0.7937(2) 0.0363(7)

C(6) 1.3812(2) 0.3085(4) 0.8482(2) 0.0376(8)

C(7) 1.2823(2) 0.1815(3) 0.7961(2) 0.0336(7)

C(8) 1.1724(2) 0.1596(3) 0.8448(2) 0.0344(8)

C(9) 1.1239(2) 0.3349(3) 0.8641(2) 0.0369(8)

C(10) 1.1158(2) 0.4580(3) 0.7824(2) 0.0369(8)

C(11) 1.2229(2) 0.4503(3) 0.7293(2) 0.0327(7)

C(12) 0.9799(3) 0.4271(4) 0.7237(2) 0.0481(9)

C(13) 0.9205(2) 0.2941(4) 0.7744(2) 0.0445(9)

C(14) 0.9880(2) 0.3276(4) 0.8732(2) 0.0414(8)

C(15) 1.0704(2) 0.0397(3) 0.7931(2) 0.0428(9)

C(16) 0.9449(3) 0.1142(4) 0.7432(2) 0.0441(9)

C(17) 1.2400(2) 0.2671(3) 0.7008(2) 0.0335(7)

C(18) 1.5873(3) 0.5149(5) 0.7925(2) 0.0544(11)

C(19) 1.4531(3) 0.3298(4) 0.6782(2) 0.0455(10)

C(20) 1.3350(3) 0.0969(4) 0.5958(2) 0.0507(11)

C(21) 1.3649(7) 0.1152(6) 0.5026(3) 0.0902(22)

C(22) 1.4944(4) 0.3925(6) 0.9969(3) 0.0704(13)

C(23) 0.8501(3) 0.2127(5) 0.9584(3) 0.0578(12)

C(24) 0.7406(4) –0.0033(9) 0.6886(4) 0.0989(23)

C(25) 1.0218(5) 0.6870(8) 0.5427(4) 0.1000(20)

* Ueq = (1/3)ΣiΣjUij ai · aj.

Ueq*

ai*a j

*

CRYSTALLOGRAPHY REPORTS Vol. 46 No. 2 2001

CRYSTALLOGRAPHIC ANALYSIS OF ROYLINE MONOHYDRATE 233

Table 3. Endocyclic torsion angles (deg)

C(17)–N–C(19)–C(4) –39.7(3) C(7)–C(8)–C(9)–C(10) 41.9(3)

C(19)–N–C(17)–C(11) 57.4(3) C(9)–C(8)–C(15)–C(16) 17.0(3)

C(2)–C(1)–C(11)–C(5) 43.6(3) C(15)–C(8)–C(9)–C(14) 28.8(3)

C(11)–C(1)–C(2)–C(3) –45.7(3) C(8)–C(9)–C(14)–C(13) –71.0(3)

C(1)–C(2)–C(3)–C(4) 54.8(3) C(8)–C(9)–C(10)–C(11) –39.0(3)

C(2)–C(3)–C(4)–C(5) –64.2(3) C(10)–C(9)–C(14)–C(13) 49.2(2)

C(5)–C(4)–C(19)–N 40.2(3) C(14)–C(9)–C(10)–C(12) –29.9(2)

C(3)–C(4)–C(5)–C(11) 61.0(3) C(9)–C(10)–C(12)–C(13) 0.6(3)

C(19)–C(4)–C(5)–C(11) –60.9(3) C(9)–C(10)–C(11)–C(17) 52.0(3)

C(4)–C(5)–C(11)–C(1) –49.6(3) C(5)–C(11)–C(17)–C(7) 53.4(2)

C(4)–C(5)–C(11)–C(17) 74.2(2) C(5)–C(11)–C(17)–N –70.1(2)

C(6)–C(5)–C(11)–C(17) –41.9(2) C(10)–C(11)–C(17)–C(7) –63.9(2)

C(11)–C(5)–C(6)–C(7) 14.6(3) C(10)–C(12)–C(13)–C(14) 29.1(3)

C(5)–C(6)–C(7)–C(17) 18.4(2) C(12)–C(13)–C(14)–C(9) –48.1(3)

C(6)–C(7)–C(17)–C(11) –45.5(2) C(16)–C(13)–C(14)–C(9) 70.4(3)

C(8)–(7)–C(17)–C(11) 73.9(2) C(14)–C(13)–C(16)–C(15) –27.8(3)

C(17)–C(7)–C(8)–C(9) –63.7(3) C(8)–C(15)–C(16)–C(13) –17.7(3)

Ring F [C(9)C(10)C(12)C(13)C(14)] exists in aC(14)-envelope conformation with the asymmetryparameter ∆Cs = 1.05, the phase angle of pseudorota-tion ∆ = 34.1°, and the maximum torsion angle φ =51.6°. The C(14) atom in this ring is disposed below the

CRYSTALLOGRAPHY REPORTS Vol. 46 No. 2 2001

plane defined by the other four atoms [the deviation is–0.738(3) Å].

The general view of the molecule shows that themolecule is folded within itself (Fig. 2). Molecularfolding of this kind is generally observed in multiple

Ow O(8)

C(22)

C(6)

O(6)

O(7) C(4)

C(18)

O(18)

C(19)

C(20)

C(21)

C(2)C(1)

O(1)

C(25)

C(11)

C(10)

C(15)

C(16)

C(12)

C(24)

O(16)

C(14)

C(13)

C(23) O(14)C(9)

C(8)C(7)

C(17)

C(5)

C(3)

Fig. 2. A general view of the molecule with atomic labeling.

234 RAJNIKANT et al.

Table 4. Geometry of intra- and intermolecular hydrogen bonds

D H A D–H(Å) H…A(Å) D…A(Å) D–H…A(°) Symmetry code

O(7) H(7O) O(8) 0.81 2.23 2.73 120 x, y, z

O(8) H(8) O(6) 0.86 1.86 2.64 148 x, y, z

Ow H(1w) O(14) 0.83 2.07 2.89 169 x, y, z

Ow H(2w) O(16) 0.82 2.06 2.84 159 2 – x, y + 1/2, 2 – z

O(18) H(18O) Ow 0.95 1.80 2.73 164 3 – x, y – 1/2, 2 – z

ring structures and is attributed mainly to the distor-tions developed in individual ring systems. The crystalstructure of Royline monohydrate is stabilized by theO–H···O type intermolecular contacts involving themolecule of crystal water. The geometries of hydrogenbonds are listed in Table 4.

ACKNOWLEDGMENTSRajnikant is grateful to B.D. Gupta, Scientist, Natu-

ral Products Chemistry Divisions, Regional ResearchLaboratory, Jammu Tawi for supplying the samples. Healso acknowledges the financial support received fromthe University Grants Commission, Government ofIndia, New Delhi, under its COSIST Research Pro-gram, project no. F.2-3/95(COS-II).

REFERENCES1. I. C. Chopra, J. D. Kohli, and K. L. Handa, Indian

J. Med. Res. 33, 139 (1945).

C

2. B. D. Gupta, private communications (Regional Rese-arch Laboratory, Jammu Tawi, India, 1996).

3. G. M. Sheldrick, SHELXS86: Program for the Solutionof Crystal Structures (Univ. of Göttingen, Göttingen,1986).

4. G. M. Sheldrick, SHELXL93: Program for the Refine-ment of Crystal Structures (Univ. of Göttingen, Göttin-gen, 1993).

5. C. K. Johnson, ORTEP-II: A Fortran Thermal EllipsoidPlot Program for Crystal Structure Illustrations, ReportORNL-5138 (Oak Ridge National Laboratory, Tennes-see, USA, 1976).

6. K. K. Bhandary, N. Ramasubbu, B. S. Joshi, et al., ActaCrystallogr., Sect. C: Cryst. Struct. Commun. 46, 1704(1990).

7. B. S. Joshi, H. K. Desai, S. W. Pelletier, and M. G. New-ton, J. Crystallogr. Spectrosc. Res. 22, 477 (1992).

8. P. W. Codding, Acta Crystallogr., Sect. B: Struct. Crys-tallogr. Cryst. Chem. B38, 2519 (1982).

9. C. Altona, H. J. Geise, and C. Romers, Tetrahedron 24,13 (1968).

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