(3R*,5′S*)-6,7-Dimeth­oxy-3-(4′-meth­oxy-6′-methyl-5′,6′,7′,8′-tetra­hydro-1,3-dioxolo[4,5-g]isoquinolin-5′-yl)isobenzofuran-1(3H)-one (racemic α-noscapine)

von Langermann, J.; Lorenz, H.; Boehm, O.; Flemming, A.; Bernsdorf, A.; Köckerling, M.; Schinzer, D.; Seidel-Morgenstern, A.

doi:10.1107/S1600536810003958

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 66| Part 3| March 2010| Page o570

doi:10.1107/S1600536810003958

Open

access

(3R,5′S)-6,7-Dimethoxy-3-(4′-methoxy-6′-methyl-5′,6′,7′,8′-tetrahydro-1,3-dioxolo[4,5-g]isoquinolin-5′-yl)isobenzofuran-1(3H)-one (racemic α-noscapine)

Jan von Langermann,^a Heike Lorenz,^a Oliver Boehm,^b Anke Flemming,^c Arne Bernsdorf,^c Martin Köckerling,^c Dieter Schinzer ^b and Andreas Seidel-Morgenstern ^a ^*

^aMax-Planck-Institute for Dynamics of Complex Technical Systems, Sandtorstrasse 1, 39106 Magdeburg, Germany, ^bMOLISA GmbH, Brenneckestrasse 20, 39118 Magdeburg, Germany, and ^cUniversity of Rostock, Department of Chemistry, Devision of Inorganic Chemistry, Albert-Einstein-Strasse 3a, D-18059 Rostock, Germany
^*Correspondence e-mail: seidel-morgenstern@mpi-magdeburg.mpg.de

(Received 21 December 2009; accepted 1 February 2010; online 10 February 2010)

In the racemic title compound, C₂₂H₂₃NO₇, the dihedral angle between the fused ring systems is 51.87 (6)°. Two of the methoxy groups are disordered over two orientations in 0.688 (5):0.312 (5) and 0.672 (15):0.328 (15) ratios. In the crystal, weak C—H⋯O interactions link the molecules.

Related literature

For the antitussive properties of S,R-noscapine [(−)-narcotin], a main alkaloid of the opium poppy, see: Bergmann & Stolzer (1956 ). For the biological activity of noscapine and related compounds, see: Aneja et al. (2006 , 2007 ); Mahmoudian et al. (2009 ); Dahlstrom et al. (1982 ); Anderson et al. (2005 ). For the crystal structure of the naturally occurring chiral molecule, see: Seetharaman et al. (1995 ).

Experimental

Crystal data

C₂₂H₂₃NO₇
M_r = 413.41
Monoclinic, P 2₁ /c
a = 15.5242 (8) Å
b = 9.3581 (5) Å
c = 13.2801 (7) Å
β = 95.781 (2)°
V = 1919.48 (17) Å³
Z = 4
Mo Kα radiation
μ = 0.11 mm⁻¹
T = 173 K
0.59 × 0.36 × 0.11 mm

Data collection

Bruker SMART CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2007 ) T_min = 0.939, T_max = 0.988
14003 measured reflections
3864 independent reflections
2989 reflections with I > 2σ(I)
R_int = 0.018

Refinement

R[F² > 2σ(F²)] = 0.057
wR(F²) = 0.169
S = 1.12
3864 reflections
310 parameters
H-atom parameters constrained
Δρ_max = 0.56 e Å⁻³
Δρ_min = −0.71 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C6—H6A⋯O1ⁱ	1.00	2.54	3.533 (3)	172
C13—H13A⋯O2ⁱⁱ	1.00	2.44	3.317 (3)	146
C18—H18A⋯O5ⁱⁱⁱ	0.95	2.34	3.120 (3)	140
Symmetry codes: (i) $[-x+2, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (ii) $[x, -y+{\script{3\over 2}}, z+{\script{1\over 2}}]$ ; (iii) $[x, -y+{\script{3\over 2}}, z-{\script{1\over 2}}]$ .

Data collection: SMART (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810003958/hb5290sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536810003958/hb5290Isup2.hkl

checkCIF report

Comment top

The antitussive properties of S,R-noscapine [(-)-narcotin], a main alkaloid of opium poppy, were investigated for several decades (e.g. Bergmann et al., 1956). Also anti-cancer properties were recently discussed. Unfortunately, the main production source of this compound is still the illegal crop growing. Therefore, for a drug-independent noscapine-source total synthesis is required, which yield in racemic alpha-noscapine (racemic mixture of S,R- and R,S-noscapine). This compound may be used as an intermediate to obtain S,R-noscapine by separation procedures. Its synthesis will be reported later.

For the biological activity of noscapine and related compounds, see: Aneja et al. (2007); Mahmoudian & Rahimi-Moghaddam (2009); Dahlstrom et al. (1982); Aneja et al. (2006); Anderson et al. (2005). For the crystal structure of the naturally occurring chiral molecule, see: Seetharaman & Rajan (1995).

Related literature top

For the antitussive properties of S,R-noscapine [(-)-narcotin], a main alkaloid of the opium poppy, see: Bergmann & Stolzer (1956). For the biological activity of noscapine and related compounds, see: Aneja et al. (2006, 2007); Mahmoudian et al. (2009); Dahlstrom et al. (1982); Anderson et al. (2005). For the crystal structure of the naturally occurring chiral molecule, see: Seetharaman et al. (1995).

Computing details top

Data collection: SMART (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top

	Fig. 1. The molecular structure of (I) with displacement ellipsoids shown at the 50% probability level. The O6—C22H₃ methoxy group is disordered on two positions.
	Fig. 2. Partial packing diagram of (I).

(3R*,5'S*)-6,7-Dimethoxy-3-(4'-methoxy-6'-methyl-5',6',7',8'- tetrahydro-1,3-dioxolo[4,5-g]isoquinolin-5'-yl)isobenzofuran- 1(3H)-one top

Crystal data top

C₂₂H₂₃NO₇	F(000) = 872
M_r = 413.41	D_x = 1.431 Mg m⁻³
Monoclinic, P2₁/c	Melting point: 501.9 K
Hall symbol: -P 2ybc	Mo Kα radiation, λ = 0.71073 Å
a = 15.5242 (8) Å	Cell parameters from 6930 reflections
b = 9.3581 (5) Å	θ = 2.5–29.9°
c = 13.2801 (7) Å	µ = 0.11 mm⁻¹
β = 95.781 (2)°	T = 173 K
V = 1919.48 (17) Å³	Block, colourless
Z = 4	0.59 × 0.36 × 0.11 mm

Data collection top

Bruker SMART CCD diffractometer	3864 independent reflections
Radiation source: fine-focus sealed tube	2989 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.018
ω scans	θ_max = 26.3°, θ_min = 3.4°
Absorption correction: multi-scan (SADABS; Bruker, 2007)	h = −18→19
T_min = 0.939, T_max = 0.988	k = −11→8
14003 measured reflections	l = −15→16

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.057	H-atom parameters constrained
wR(F²) = 0.169	w = 1/[σ²(F_o²) + (0.0785P)² + 1.390P] where P = (F_o² + 2F_c²)/3
S = 1.12	(Δ/σ)_max = 0.001
3864 reflections	Δρ_max = 0.56 e Å⁻³
310 parameters	Δρ_min = −0.71 e Å⁻³
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0057 (18)

Crystal data top

C₂₂H₂₃NO₇	V = 1919.48 (17) Å³
M_r = 413.41	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 15.5242 (8) Å	µ = 0.11 mm⁻¹
b = 9.3581 (5) Å	T = 173 K
c = 13.2801 (7) Å	0.59 × 0.36 × 0.11 mm
β = 95.781 (2)°

Data collection top

Bruker SMART CCD diffractometer	3864 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2007)	2989 reflections with I > 2σ(I)
T_min = 0.939, T_max = 0.988	R_int = 0.018
14003 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.057	0 restraints
wR(F²) = 0.169	H-atom parameters constrained
S = 1.12	Δρ_max = 0.56 e Å⁻³
3864 reflections	Δρ_min = −0.71 e Å⁻³
310 parameters

Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq	Occ. (<1)
N1	0.73446 (12)	0.3640 (2)	0.27455 (14)	0.0344 (5)
O1	1.04337 (10)	0.66824 (18)	0.09956 (12)	0.0386 (4)
O2	0.95148 (11)	0.68699 (18)	−0.04776 (12)	0.0404 (4)
O3	0.98826 (10)	0.53115 (19)	0.28872 (11)	0.0374 (4)
O4	0.79757 (10)	0.49937 (17)	0.46248 (11)	0.0342 (4)
O5	0.69655 (18)	0.5011 (2)	0.56862 (18)	0.0843 (9)
C1	1.03115 (17)	0.7361 (3)	0.00278 (19)	0.0428 (6)
H1A	1.0296	0.8412	0.0111	0.051*
H1B	1.0796	0.7120	−0.0373	0.051*
C2	0.90820 (15)	0.6242 (2)	0.02642 (16)	0.0324 (5)
C3	0.96312 (14)	0.6128 (2)	0.11444 (17)	0.0305 (5)
C4	0.93703 (14)	0.5473 (2)	0.19924 (16)	0.0287 (5)
C5	0.85049 (13)	0.4988 (2)	0.19361 (15)	0.0284 (5)
C6	0.81858 (13)	0.4371 (2)	0.28879 (16)	0.0293 (5)
H6A	0.8627	0.3669	0.3183	0.035*
C7	0.70645 (16)	0.3236 (3)	0.16978 (19)	0.0412 (6)
H7A	0.6475	0.2824	0.1660	0.049*
H7B	0.7459	0.2496	0.1473	0.049*
C8	0.70633 (15)	0.4513 (3)	0.10059 (18)	0.0412 (6)
H8A	0.6858	0.4225	0.0305	0.049*
H8B	0.6664	0.5251	0.1224	0.049*
C9	0.79610 (14)	0.5116 (2)	0.10352 (16)	0.0323 (5)
C10	0.82522 (14)	0.5736 (2)	0.01770 (16)	0.0343 (5)
H10A	0.7889	0.5805	−0.0441	0.041*
C11A	1.07435 (17)	0.4888 (4)	0.2848 (2)	0.0634 (9)
H11A	1.1034	0.4824	0.3537	0.095*
H11B	1.1042	0.5592	0.2461	0.095*
H11C	1.0757	0.3953	0.2518	0.095*
C13	0.81365 (13)	0.5602 (2)	0.36560 (15)	0.0279 (5)
H13A	0.8699	0.6132	0.3730	0.033*
C14	0.72208 (18)	0.5464 (3)	0.4926 (2)	0.0451 (6)
C15	0.68646 (15)	0.6537 (2)	0.41869 (19)	0.0379 (6)
C16	0.61460 (19)	0.7398 (3)	0.4222 (3)	0.0668 (10)
C17	0.59567 (16)	0.8363 (3)	0.3418 (2)	0.0511 (7)
C18	0.64984 (15)	0.8462 (2)	0.26480 (17)	0.0358 (5)
H18A	0.6367	0.9123	0.2111	0.043*
C19	0.72308 (15)	0.7602 (2)	0.26562 (16)	0.0348 (5)
H19A	0.7604	0.7682	0.2134	0.042*
C20	0.74082 (13)	0.6636 (2)	0.34276 (15)	0.0266 (5)
C12	0.73227 (19)	0.2382 (3)	0.3401 (2)	0.0483 (7)
H12A	0.6754	0.1924	0.3286	0.073*
H12B	0.7428	0.2677	0.4110	0.073*
H12C	0.7772	0.1705	0.3244	0.073*
O6A	0.57726 (16)	0.7471 (3)	0.51826 (17)	0.0462 (9)	0.688 (5)
C22A	0.4909 (3)	0.7090 (9)	0.5089 (4)	0.0661 (17)	0.688 (5)
H22A	0.4731	0.6860	0.5758	0.099*	0.688 (5)
H22B	0.4822	0.6252	0.4647	0.099*	0.688 (5)
H22C	0.4559	0.7886	0.4795	0.099*	0.688 (5)
O6B	0.5332 (3)	0.6839 (5)	0.4441 (4)	0.0319 (17)	0.312 (5)
C22B	0.5107 (6)	0.7879 (10)	0.5178 (7)	0.033 (2)	0.312 (5)
H22D	0.4482	0.8054	0.5088	0.050*	0.312 (5)
H22E	0.5417	0.8774	0.5083	0.050*	0.312 (5)
H22F	0.5271	0.7513	0.5862	0.050*	0.312 (5)
C21A	0.4969 (5)	1.0087 (11)	0.2733 (6)	0.0490 (17)	0.672 (15)
H21A	0.4501	1.0716	0.2903	0.074*	0.672 (15)
H21B	0.4749	0.9430	0.2193	0.074*	0.672 (15)
H21C	0.5439	1.0664	0.2504	0.074*	0.672 (15)
O7A	0.5288 (3)	0.9287 (5)	0.3606 (5)	0.0431 (15)	0.672 (15)
C21B	0.4989 (11)	1.0049 (18)	0.2305 (13)	0.050 (4)	0.328 (15)
H21D	0.4368	1.0183	0.2108	0.075*	0.328 (15)
H21E	0.5278	0.9793	0.1708	0.075*	0.328 (15)
H21F	0.5237	1.0937	0.2597	0.075*	0.328 (15)
O7B	0.5109 (4)	0.8924 (8)	0.3042 (11)	0.039 (3)	0.328 (15)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.0349 (10)	0.0345 (10)	0.0347 (10)	−0.0060 (8)	0.0082 (8)	−0.0070 (8)
O1	0.0367 (9)	0.0398 (9)	0.0405 (9)	−0.0031 (7)	0.0103 (7)	0.0054 (7)
O2	0.0446 (10)	0.0406 (9)	0.0373 (9)	0.0050 (7)	0.0108 (7)	0.0095 (7)
O3	0.0266 (8)	0.0546 (10)	0.0311 (8)	0.0044 (7)	0.0038 (6)	−0.0008 (7)
O4	0.0374 (9)	0.0410 (9)	0.0244 (8)	0.0063 (7)	0.0044 (6)	−0.0009 (7)
O5	0.124 (2)	0.0637 (14)	0.0779 (15)	0.0484 (14)	0.0743 (15)	0.0347 (12)
C1	0.0502 (14)	0.0356 (13)	0.0443 (14)	0.0007 (11)	0.0134 (11)	0.0089 (11)
C2	0.0410 (12)	0.0273 (11)	0.0304 (11)	0.0100 (9)	0.0103 (9)	0.0017 (9)
C3	0.0299 (11)	0.0259 (10)	0.0369 (12)	0.0035 (8)	0.0092 (9)	−0.0031 (9)
C4	0.0296 (11)	0.0293 (11)	0.0279 (10)	0.0043 (8)	0.0054 (8)	−0.0046 (8)
C5	0.0284 (11)	0.0284 (10)	0.0293 (11)	0.0052 (8)	0.0067 (8)	−0.0053 (9)
C6	0.0267 (10)	0.0311 (11)	0.0309 (11)	0.0031 (8)	0.0064 (8)	−0.0033 (9)
C7	0.0352 (13)	0.0444 (14)	0.0444 (14)	−0.0069 (10)	0.0058 (10)	−0.0143 (11)
C8	0.0288 (12)	0.0584 (16)	0.0362 (13)	0.0021 (11)	0.0018 (9)	−0.0088 (11)
C9	0.0305 (11)	0.0356 (12)	0.0315 (11)	0.0082 (9)	0.0065 (9)	−0.0059 (9)
C10	0.0337 (12)	0.0395 (13)	0.0299 (11)	0.0127 (10)	0.0037 (9)	−0.0016 (9)
C11A	0.0348 (14)	0.113 (3)	0.0433 (15)	0.0206 (16)	0.0076 (11)	0.0161 (17)
C13	0.0259 (10)	0.0338 (11)	0.0244 (10)	−0.0008 (8)	0.0046 (8)	−0.0020 (8)
C14	0.0556 (16)	0.0397 (13)	0.0443 (14)	0.0146 (12)	0.0262 (12)	0.0046 (11)
C15	0.0360 (12)	0.0314 (12)	0.0492 (14)	0.0029 (9)	0.0182 (10)	0.0049 (10)
C16	0.0508 (17)	0.0533 (17)	0.105 (3)	0.0212 (14)	0.0502 (17)	0.0351 (17)
C17	0.0291 (12)	0.0369 (13)	0.090 (2)	0.0080 (10)	0.0183 (13)	0.0169 (14)
C18	0.0405 (13)	0.0312 (11)	0.0342 (12)	0.0024 (10)	−0.0038 (10)	−0.0041 (9)
C19	0.0423 (13)	0.0368 (12)	0.0265 (11)	0.0052 (10)	0.0091 (9)	−0.0039 (9)
C20	0.0249 (10)	0.0290 (11)	0.0258 (10)	−0.0035 (8)	0.0020 (8)	−0.0081 (8)
C12	0.0565 (16)	0.0399 (14)	0.0502 (15)	−0.0148 (12)	0.0127 (12)	−0.0041 (11)
O6A	0.0358 (16)	0.076 (2)	0.0288 (14)	0.0116 (13)	0.0118 (10)	0.0064 (12)
C22A	0.040 (3)	0.114 (5)	0.046 (3)	−0.010 (3)	0.013 (2)	0.017 (3)
O6B	0.027 (3)	0.031 (3)	0.042 (3)	−0.0057 (19)	0.019 (2)	−0.004 (2)
C22B	0.027 (5)	0.038 (5)	0.035 (4)	0.003 (3)	0.007 (3)	−0.002 (4)
C21A	0.037 (2)	0.059 (3)	0.053 (4)	0.012 (2)	0.014 (3)	0.028 (4)
O7A	0.0393 (17)	0.055 (2)	0.037 (3)	0.0203 (15)	0.0117 (17)	0.014 (2)
C21B	0.041 (5)	0.040 (5)	0.072 (10)	0.017 (4)	0.017 (7)	0.033 (8)
O7B	0.031 (3)	0.041 (4)	0.044 (7)	0.008 (2)	0.004 (3)	0.009 (3)

Geometric parameters (Å, º) top

N1—C7	1.465 (3)	C13—H13A	1.0000
N1—C12	1.466 (3)	C14—C15	1.472 (4)
N1—C6	1.469 (3)	C15—C16	1.381 (3)
O1—C3	1.382 (3)	C15—C20	1.382 (3)
O1—C1	1.429 (3)	C16—C17	1.406 (4)
O2—C2	1.379 (3)	C16—O6B	1.425 (5)
O2—C1	1.423 (3)	C16—O6A	1.455 (4)
O3—C4	1.370 (3)	C17—C18	1.391 (4)
O3—C11A	1.400 (3)	C17—O7A	1.392 (4)
O4—C14	1.350 (3)	C17—O7B	1.457 (7)
O4—C13	1.451 (2)	C18—C19	1.392 (3)
O5—C14	1.199 (3)	C18—H18A	0.9500
C1—H1A	0.9900	C19—C20	1.373 (3)
C1—H1B	0.9900	C19—H19A	0.9500
C2—C10	1.366 (3)	C12—H12A	0.9800
C2—C3	1.380 (3)	C12—H12B	0.9800
C3—C4	1.378 (3)	C12—H12C	0.9800
C4—C5	1.413 (3)	O6A—C22A	1.382 (6)
C5—C9	1.398 (3)	C22A—H22A	0.9800
C5—C6	1.517 (3)	C22A—H22B	0.9800
C6—C13	1.546 (3)	C22A—H22C	0.9800
C6—H6A	1.0000	O6B—C22B	1.447 (10)
C7—C8	1.508 (4)	C22B—H22D	0.9800
C7—H7A	0.9900	C22B—H22E	0.9800
C7—H7B	0.9900	C22B—H22F	0.9800
C8—C9	1.500 (3)	C21A—O7A	1.426 (7)
C8—H8A	0.9900	C21A—H21A	0.9800
C8—H8B	0.9900	C21A—H21B	0.9800
C9—C10	1.394 (3)	C21A—H21C	0.9800
C10—H10A	0.9500	C21B—O7B	1.436 (14)
C11A—H11A	0.9800	C21B—H21D	0.9800
C11A—H11B	0.9800	C21B—H21E	0.9800
C11A—H11C	0.9800	C21B—H21F	0.9800
C13—C20	1.496 (3)

C7—N1—C12	109.51 (19)	C6—C13—H13A	109.5
C7—N1—C6	114.66 (17)	O5—C14—O4	120.3 (2)
C12—N1—C6	111.77 (19)	O5—C14—C15	132.0 (2)
C3—O1—C1	104.81 (18)	O4—C14—C15	107.71 (19)
C2—O2—C1	105.30 (18)	C16—C15—C20	122.7 (2)
C4—O3—C11A	118.17 (18)	C16—C15—C14	128.8 (2)
C14—O4—C13	111.50 (17)	C20—C15—C14	108.4 (2)
O2—C1—O1	108.11 (18)	C15—C16—C17	117.2 (2)
O2—C1—H1A	110.1	C15—C16—O6B	121.9 (3)
O1—C1—H1A	110.1	C17—C16—O6B	105.6 (3)
O2—C1—H1B	110.1	C15—C16—O6A	116.8 (3)
O1—C1—H1B	110.1	C17—C16—O6A	124.3 (2)
H1A—C1—H1B	108.4	C18—C17—O7A	127.4 (3)
C10—C2—O2	127.6 (2)	C18—C17—C16	120.3 (2)
C10—C2—C3	122.8 (2)	O7A—C17—C16	111.4 (3)
O2—C2—C3	109.5 (2)	C18—C17—O7B	108.4 (5)
C4—C3—C2	121.3 (2)	C16—C17—O7B	127.2 (4)
C4—C3—O1	128.8 (2)	C17—C18—C19	120.6 (2)
C2—C3—O1	109.82 (19)	C17—C18—H18A	119.7
O3—C4—C3	124.4 (2)	C19—C18—H18A	119.7
O3—C4—C5	118.44 (19)	C20—C19—C18	119.3 (2)
C3—C4—C5	117.1 (2)	C20—C19—H19A	120.4
C9—C5—C4	120.45 (19)	C18—C19—H19A	120.4
C9—C5—C6	121.71 (19)	C19—C20—C15	119.8 (2)
C4—C5—C6	117.82 (19)	C19—C20—C13	131.89 (18)
N1—C6—C5	115.49 (18)	C15—C20—C13	108.27 (19)
N1—C6—C13	109.24 (16)	N1—C12—H12A	109.5
C5—C6—C13	107.95 (17)	N1—C12—H12B	109.5
N1—C6—H6A	108.0	H12A—C12—H12B	109.5
C5—C6—H6A	108.0	N1—C12—H12C	109.5
C13—C6—H6A	108.0	H12A—C12—H12C	109.5
N1—C7—C8	110.9 (2)	H12B—C12—H12C	109.5
N1—C7—H7A	109.5	C22A—O6A—C16	112.2 (3)
C8—C7—H7A	109.5	O6A—C22A—H22A	109.5
N1—C7—H7B	109.5	O6A—C22A—H22B	109.5
C8—C7—H7B	109.5	H22A—C22A—H22B	109.5
H7A—C7—H7B	108.1	O6A—C22A—H22C	109.5
C9—C8—C7	109.8 (2)	H22A—C22A—H22C	109.5
C9—C8—H8A	109.7	H22B—C22A—H22C	109.5
C7—C8—H8A	109.7	C16—O6B—C22B	99.8 (5)
C9—C8—H8B	109.7	O6B—C22B—H22D	109.5
C7—C8—H8B	109.7	O6B—C22B—H22E	109.5
H8A—C8—H8B	108.2	H22D—C22B—H22E	109.5
C10—C9—C5	121.2 (2)	O6B—C22B—H22F	109.5
C10—C9—C8	120.8 (2)	H22D—C22B—H22F	109.5
C5—C9—C8	118.0 (2)	H22E—C22B—H22F	109.5
C2—C10—C9	117.1 (2)	O7A—C21A—H21A	109.5
C2—C10—H10A	121.5	O7A—C21A—H21B	109.5
C9—C10—H10A	121.5	H21A—C21A—H21B	109.5
O3—C11A—H11A	109.5	O7A—C21A—H21C	109.5
O3—C11A—H11B	109.5	H21A—C21A—H21C	109.5
H11A—C11A—H11B	109.5	H21B—C21A—H21C	109.5
O3—C11A—H11C	109.5	C17—O7A—C21A	112.6 (4)
H11A—C11A—H11C	109.5	O7B—C21B—H21D	109.5
H11B—C11A—H11C	109.5	O7B—C21B—H21E	109.5
O4—C13—C20	103.85 (15)	H21D—C21B—H21E	109.5
O4—C13—C6	108.49 (17)	O7B—C21B—H21F	109.5
C20—C13—C6	115.78 (17)	H21D—C21B—H21F	109.5
O4—C13—H13A	109.5	H21E—C21B—H21F	109.5
C20—C13—H13A	109.5	C21B—O7B—C17	123.3 (8)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C6—H6A···O1ⁱ	1.00	2.54	3.533 (3)	172
C13—H13A···O2ⁱⁱ	1.00	2.44	3.317 (3)	146
C18—H18A···O5ⁱⁱⁱ	0.95	2.34	3.120 (3)	140

Symmetry codes: (i) −x+2, y−1/2, −z+1/2; (ii) x, −y+3/2, z+1/2; (iii) x, −y+3/2, z−1/2.

Experimental details

Crystal data
Chemical formula	C₂₂H₂₃NO₇
M_r	413.41
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	173
a, b, c (Å)	15.5242 (8), 9.3581 (5), 13.2801 (7)
β (°)	95.781 (2)
V (Å³)	1919.48 (17)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.11
Crystal size (mm)	0.59 × 0.36 × 0.11

Data collection
Diffractometer	Bruker SMART CCD diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2007)
T_min, T_max	0.939, 0.988
No. of measured, independent and observed [I > 2σ(I)] reflections	14003, 3864, 2989
R_int	0.018
(sin θ/λ)_max (Å⁻¹)	0.624

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.057, 0.169, 1.12
No. of reflections	3864
No. of parameters	310
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.56, −0.71

Computer programs: SMART (Bruker, 2007), SAINT (Bruker, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C6—H6A···O1ⁱ	1.00	2.54	3.533 (3)	172
C13—H13A···O2ⁱⁱ	1.00	2.44	3.317 (3)	146
C18—H18A···O5ⁱⁱⁱ	0.95	2.34	3.120 (3)	140

Symmetry codes: (i) −x+2, y−1/2, −z+1/2; (ii) x, −y+3/2, z+1/2; (iii) x, −y+3/2, z−1/2.

Acknowledgements

This work was funded by the EC Seventh Framework Programme for Research and Technological Development (FP7), Project: IntEnant (contract number: NMP2-SL-2008–214129).

References

Anderson, J., Ting, A., Boozer, S., Brunden, K., Crumrine, C., Danzig, J., Dent, T., Faga, L., Harrington, J., Hodrick, W., Murphy, S., Pawlowski, G., Perry, R., Raber, A., Rundlett, S., Stricker-Krongrad, A., Wang, J. & Bennani, Y. (2005). J. Med. Chem. 48, 7096–7098. Web of Science CrossRef PubMed CAS Google Scholar
Aneja, R., Dhiman, N., Idnani, J., Awasthi, A., Arora, S., Chandra, R. & Joshi, H. (2007). Cancer Chemother. Pharm. 60, 831–839. Web of Science CrossRef CAS Google Scholar
Aneja, R., Vangapandu, S. & Joshi, H. (2006). Bioorg. Med. Chem. 14, 8352–8358. Web of Science CrossRef PubMed CAS Google Scholar
Bergmann, M. & Stolzer, H. (1956). Wien. Med. Wochenschr. 106, 232–233. PubMed CAS Google Scholar
Bruker (2007). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Dahlstrom, B., Mellstrand, T., Lofdahl, C. & Johannsson, M. (1982). Eur. J. Clin. Pharmacol. 22, 535–539. CrossRef CAS PubMed Web of Science Google Scholar
Mahmoudian, M. & Rahimi-Moghaddam, P. (2009). Recent Patents on Anti-Cancer Drug Discovery, 4, 92–97 Google Scholar
Seetharaman, J. & Rajan, S. (1995). Z. Kristallogr. 210, 111–113. CrossRef CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 66| Part 3| March 2010| Page o570

doi:10.1107/S1600536810003958

Open

access

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Plain Text

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Plain Text

Search IUCr Journals		doi		Advanced search
Author		volume	page

organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

(3R*,5′S*)-6,7-Dimeth­­oxy-3-(4′-meth­­oxy-6′-methyl-5′,6′,7′,8′-tetra­hydro-1,3-dioxolo[4,5-g]isoquinolin-5′-yl)isobenzo­furan-1(3H)-one (racemic α-noscapine)

Related literature

Experimental

Crystal data

Data collection

Refinement

Supporting information

Acknowledgements

References

organic compounds

(3R,5′S)-6,7-Dimethoxy-3-(4′-methoxy-6′-methyl-5′,6′,7′,8′-tetrahydro-1,3-dioxolo[4,5-g]isoquinolin-5′-yl)isobenzofuran-1(3H)-one (racemic α-noscapine)