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Di­hydro­berberine (systematic name: 9,10-dimeth­oxy-6,8-dihydro-5H-1,3-dioxolo[4,5-g]iso­quinolino­[3,2-a]iso­quinoline), C20H19NO4, a reduced form of pharmacologically important berberine, crystallizes from ethanol without inter­stitial solvent. The mol­ecule shows a dihedral angle of 27.94 (5)° between the two arene rings at the ends of the mol­ecule, owing to the partial saturation of the inner quinolizine ring system. Although lacking classical O—H or N—H donors, the packing in the crystalline state is clearly governed by C—H...N and C—H...O hydrogen bonds involving the two acetal-type C—H bonds of the 1,3-dioxole ring. Each di­hydro­berberine mol­ecule is engaged in four hydrogen bonds with neighbouring mol­ecules, twice as donor and twice as acceptor, thus forming a two-dimensional sheet network that lies parallel to the (100) plane.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S2053229614003751/fn3163sup1.cif
Contains datablocks I, global

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S2053229614003751/fn3163Isup2.hkl
Contains datablock I

cml

Chemical Markup Language (CML) file https://doi.org/10.1107/S2053229614003751/fn3163Isup3.cml
Supplementary material

CCDC reference: 987722

Introduction top

Di­hydro­berberine (see Scheme 1, parts a and b) is a reduced form of berberine (see Scheme 1, part c), an iso­quinoline alkaloid isolated from shrubs of the genus berberis. It is a very important pharmacological compound with a diverse range of biological activities (Amin et al., 1969; Akhter et al., 1979; Swabb et al. 1981; Sack & Froehlich, 1982; Sun et al., 1988; Yuan et al. 1994; Birdsall & Kelly, 1997; Gibbs & Seddon, 2000). With a change of only one degree of unsaturation in its chemical structure, di­hydro­berberine does not show diminished biological activity but rather has improved results in some cases. Due to its enhanced bioavailability, di­hydro­berberine improves in vivo efficacy in terms of counteracting increased adiposity and insulin resistance in high-fat rodents (Turner et al., 2008). It has also been found to be effective in site-specific sustained release of drugs to the brain by undergoing in vivo transformation into berberine (Bodor et al., 1981; Brewster & Bodor, 1983; Bodor & Brewster, 1983). Further derivatization of di­hydro­berberine by the introduction of hy­droxy and cyano groups onto the reduced ring leads to active anti­malarials (Vennerstrom & Klayman, 1988), avian myeblastosis virus inhibitors (AMV–RT) (Kusumoto et al., 1991), anti­tumour agents (Kim et al., 1997), anti­fungals (Dostál et al., 1999), mitogen-activated protein kinase inhibitors (MAPKK) (Jang et al., 2002), promoters of glucose metabolism and insulin secretion (Xu et al., 2011) and CD36 antagonists (Li et al., 2010). Di­hydro­berberine has found use as an inter­mediate in the synthesis of substituted berberine analogues which were found to act as anti­cancer agents (Zhang et al., 2012), pancreatic lipase inhibitory agents (Mohammad et al., 2013), anti­fungal agents (Li et al., 2013), Toxoplasma gondii inhibitors (Krivogorsky et al., 2012) and mitochondria-targeted anti­oxidants (Lyamzaev et al., 2011), and which have shown activity as anti­babesial (Subeki et al., 2005) and anti­leishmania agents (Marquis et al., 2003) and as HIV-1 RT inhibitors (Vennerstrom et al., 1990).

With such varied and important biological activity obtained through a minor change in the unsaturation of the compound, we were motivated to characterize di­hydro­berberine structurally by X-ray crystallography. Surprisingly, while the structure of berberine crystallized with a variety of counter-anions has been reported (Moniot & Shamma, 1979; Abadi et al., 1984; Kariuki & Jones, 1995; Marek, Sečkářová et al., 2003; Tong et al., 2010; Chahine et al., 2011), as have the structures of an assortment of 8-substituted derivatives of di­hydro­berberine (Man et al., 2001; Marek, Hulová et al., 2003; Dostál et al., 2004; Maier et al., 2010; Man et al., 2011), a determination of the crystal structure of di­hydro­berberine itself has not been undertaken. Herein, we report its crystal structure from X-ray diffraction data at 150 K.

Experimental top

Synthesis and crystallization top

To a stirred solution of berberine chloride (3.71 g, 10 mmol) and K2CO3 (3.6 g, 30 mmol) in MeOH (125 ml), a 5% NaOH solution (5 ml) containing NaBH4 (0.3 g, 7.5 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 1 h, and the precipitated product was filtered and washed with 30% EtOH (20 ml) followed by 80% EtOH (20 ml). It was then recrystallized from absolute EtOH (400 ml) to afford 2.8 g (83%) of (I) as green–brown needles [Pale-yellow prisms given in CIF tables - please clarify]. MS m/z: 340. 1H NMR (CDCl3, δ, p.p.m.): 7.19 (s, 1H), 6.76 (s, 2H), 6.59 (s, 1H), 5.97 (s, 1H), 5.96 (s, 2H), 4.34 (s, 2H), 3.86 (s, 6H), 3.15 (t, 2H), 2.89 (t, 2H).

Refinement top

Crystal data, data collection and structure refinement details are summarized in Table 1. H atoms were identified in the final difference map, and their positions were refined with isotropic displacement parameters that were approximately 1.2–1.5 times the equivalent displacement parameters of the C atoms to which they were attached.

Results and discussion top

The structure of di­hydro­berberine is derived from berberine (Fig. 1) by reduction of the N7—C8 bond. The partial saturation of the quinolizine ring system at the C5—C6 and N7—C8 positions induces a bending of the fused-ring system (see Scheme 1, part b and Fig. 2), with the fully unsaturated arene rings at the ends of the molecule disposed at a dihedral angle of 27.9°. The corresponding angle in berberine is approximately 12.5° (Kariuki & Jones, 1995), owing to the unsaturation at the N7—C8 bond. Atoms C6 and C8 are both folded up towards the top side of the di­hydro­quinolizine ring system, as presented in the figure, such that the angle between the C5/C4a/C13b/C13a/N7 and C5/C6/N7 mean planes is 37.0°, and that between the N7/C13a/C13/C12a/C8a and N7/C8/C8a mean planes is 41.3°. The tertiary N atom is slightly pyramidal, displaced by 0.315 Å from the plane of the three surrounding C atoms. As such, it constitutes a chiral centre. The molecule depicted in Fig. 2 shows the S configuration; the opposite enanti­omer necessarily occurs in the unit cell as well, related by an inversion centre to the molecule shown, as the space group is centric.

Importantly, the unit-cell packing arrangement for di­hydro­berberine occurs as two-dimensional sheets, the formation of which is governed by a network of hydrogen bonds, despite the absence of a typical O—H or N—H donor in the molecule. Here, the acetal-type –CH2– group of the 1,3-dioxole ring is sufficiently activated by the geminal O atoms that both of its H atoms function as hydrogen-bond donors. One pair of hydrogen-bond inter­actions occurs between this –CH2– group and the tertiary amine N atom of a neighbouring molecule, the two molecules being disposed about a centre of symmetry as a pair of enanti­omers. Such pairs of molecules are easily seen (Fig. 3 [Should this be Fig. 2?]) situated along the a edges of the unit cell, the mid-point of which is coincident with the inversion centre. A second set of hydrogen bonds is formed between the other H atom of the acetal-type –CH2– group and the meth­oxy O atom of another molecule further along the c axis and related to the first molecule by a 21 screw axis. Each enanti­omeric pair of di­hydro­berberine molecules, typified by the one at the very centre of the unit-cell diagram in Fig. 3 [Fig. 2?], enjoys four hydrogen bonds of this second type, one at each corner of the diad, such that the network is extended above and below in the direction of the b axis.

The donor–acceptor distance in the first type of hydrogen bond noted above (C2···N7) is 3.5326 (17) Å, and the D—H···A angle is 152.5 (11)°. For the second set of hydrogen bonds involving a meth­oxy O atom as acceptor, the corresponding values are 3.3031 (15) Å and 156.2 (11)°. These distances and angles are typical of a `weak hydrogen bond', as defined by Desiraju & Steiner (1999). The occurrence of acetal-type C—H···O hydrogen bonds has been shown to be important in governing the properties of polymethyl­ene glycol and related oligomeric and small molecules. In di­methyl­ene glycol, HOCH2OCH2OH, two inter­nal hydrogen bonds of this type occur in the energy-minimized structure and have been computationally assessed as conferring approximately 2.65 kcal mol-1 (1 kcal mol-1 = 4.184 kJ mol-1) of stabilization per hydrogen bond (Martin & Miller, 2009). Although individually weak as hydrogen bonds, the collective effect of multiple C—H···X bonds of this type becomes important. It has been assumed that the therapeutic efficacy of berberine arises from a capacity to function as an inter­calator into DNA. The foregoing observation of C—H···X (X = O or N) hydrogen bonds in the crystal packing of di­hydro­berberine suggests the possibility that analogous hydrogen bonds may exert themselves in the inter­action of berberine (and variants thereof) with DNA, in addition to the ππ stacking that occurs upon inter­calation.

Related literature top

For related literature, see: Abadi et al. (1984); Akhter et al. (1979); Amin et al. (1969); Birdsall & Kelly (1997); Bodor & Brewster (1983); Bodor et al. (1981); Brewster & Bodor (1983); Chahine et al. (2011); Desiraju & Steiner (1999); Dostál et al. (1999, 2004); Gibbs & Seddon (2000); Jang et al. (2002); Kariuki & Jones (1995); Kim et al. (1997); Krivogorsky et al. (2012); Kusumoto et al. (1991); Li et al. (2010, 2013); Lyamzaev (2011); Maier et al. (2010); Man et al. (2001, 2011); Marek, Hulová, Dostál & Marek (2003); Marquis et al. (2003); Martin & Miller (2009); Mohammad et al. (2013); Moniot & Shamma (1979); Sack & Froehlich (1982); Subeki, Matsuura, Takahashi, Yamasaki, Yamato, Maede, Katakura, Suzuki, Trimurningsih, Chairul & Yoshihara (2005); Sun et al. (1988); Swabb et al. (1981); Tong et al. (2010); Turner et al. (2008); Vennerstrom & Klayman (1988); Vennerstrom et al. (1990); Xu et al. (2011); Yuan et al. (1994); Zhang et al. (2012).

Computing details top

Data collection: APEX2 (Bruker, 2010); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); 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
[Figure 1] Fig. 1. The molecular structure of dihydroberberine, showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
[Figure 2] Fig. 2. A cell-packing diagram for dihydroberberine, with weak hydrogen bonds indicated by dashed lines.
9,10-Dimethoxy-6,8-dihydro-5H-1,3-dioxolo[4,5-g]isoquinolino[3,2-a]isoquinoline top
Crystal data top
C20H19NO4F(000) = 712
Mr = 337.36Dx = 1.377 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 6.9562 (15) ÅCell parameters from 9822 reflections
b = 8.3067 (17) Åθ = 2.5–29.5°
c = 28.343 (6) ŵ = 0.10 mm1
β = 96.458 (3)°T = 150 K
V = 1627.3 (6) Å3Needle, green–brown
Z = 40.30 × 0.26 × 0.10 mm
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
3120 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.037
ϕ and ω scansθmax = 26.4°, θmin = 2.6°
Absorption correction: multi-scan
(SADABS; Sheldrick, 2009)
h = 88
Tmin = 0.850, Tmax = 0.990k = 1010
24555 measured reflectionsl = 3335
3339 independent reflections
Refinement top
Refinement on F2Hydrogen site location: difference Fourier map
Least-squares matrix: fullAll H-atom parameters refined
R[F2 > 2σ(F2)] = 0.041 w = 1/[σ2(Fo2) + (0.0593P)2 + 0.474P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.104(Δ/σ)max < 0.001
S = 1.06Δρmax = 0.26 e Å3
3339 reflectionsΔρmin = 0.36 e Å3
303 parametersExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
72 restraintsExtinction coefficient: 0.046 (3)
Crystal data top
C20H19NO4V = 1627.3 (6) Å3
Mr = 337.36Z = 4
Monoclinic, P21/cMo Kα radiation
a = 6.9562 (15) ŵ = 0.10 mm1
b = 8.3067 (17) ÅT = 150 K
c = 28.343 (6) Å0.30 × 0.26 × 0.10 mm
β = 96.458 (3)°
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
3339 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 2009)
3120 reflections with I > 2σ(I)
Tmin = 0.850, Tmax = 0.990Rint = 0.037
24555 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.04172 restraints
wR(F2) = 0.104All H-atom parameters refined
S = 1.06Δρmax = 0.26 e Å3
3339 reflectionsΔρmin = 0.36 e Å3
303 parameters
Special details top

Experimental. The diffraction data were obtained from 3 sets of 400 frames, each of width 0.5° in ω, collected at ϕ = 0.00, 90.00 and 180.00°, and 2 sets of 800 frames, each of width 0.45° in ϕ, collected at ω = -30.00 and 210.00°. The scan time was 60 sec/frame.

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
xyzUiso*/Ueq
O10.74498 (12)0.89863 (11)0.09389 (3)0.0290 (2)
O30.43038 (12)0.85112 (11)0.12696 (3)0.0282 (2)
O90.58292 (12)0.59221 (9)0.24003 (3)0.0236 (2)
O100.84226 (12)0.77577 (10)0.29163 (3)0.0266 (2)
N70.46787 (13)0.67091 (11)0.09423 (3)0.0210 (2)
C20.60588 (18)0.93356 (15)0.13430 (4)0.0270 (3)
H2A0.653 (2)0.8937 (17)0.1624 (5)0.026 (3)*
H2B0.579 (2)1.0513 (19)0.1352 (5)0.030 (4)*
C3a0.44450 (17)0.82606 (13)0.07873 (4)0.0230 (3)
C40.30567 (17)0.77169 (14)0.05198 (4)0.0248 (3)
H40.169 (2)0.7508 (19)0.0663 (5)0.036 (4)*
C4a0.36090 (16)0.74528 (13)0.00335 (4)0.0222 (2)
C50.21335 (17)0.69133 (16)0.02836 (4)0.0275 (3)
H5B0.152 (2)0.7900 (19)0.0431 (5)0.034 (4)*
H5A0.104 (2)0.6334 (19)0.0102 (5)0.034 (4)*
C60.30798 (18)0.58474 (15)0.06752 (4)0.0269 (3)
H6A0.356 (2)0.483 (2)0.0539 (5)0.034 (4)*
H6B0.215 (2)0.5542 (18)0.0906 (5)0.029 (3)*
C80.54753 (18)0.58566 (14)0.13716 (4)0.0242 (3)
H8A0.615 (2)0.4872 (19)0.1281 (5)0.030 (4)*
H8B0.438 (2)0.5517 (17)0.1536 (5)0.027 (3)*
C8a0.68522 (15)0.69326 (13)0.16752 (4)0.0199 (2)
C90.70076 (15)0.69167 (12)0.21664 (4)0.0199 (2)
C100.84150 (16)0.78621 (13)0.24334 (4)0.0207 (2)
C110.96563 (16)0.88100 (14)0.21999 (4)0.0233 (2)
H111.062 (2)0.9454 (18)0.2374 (5)0.026 (3)*
C12a0.80743 (15)0.79218 (13)0.14370 (4)0.0212 (2)
C120.94666 (16)0.88470 (14)0.17061 (4)0.0239 (3)
H121.028 (2)0.9530 (18)0.1544 (5)0.027 (3)*
C13b0.55134 (16)0.77202 (13)0.01702 (4)0.0203 (2)
C130.77269 (16)0.80068 (14)0.09234 (4)0.0222 (2)
H130.862 (2)0.8640 (17)0.0765 (5)0.026 (3)*
C13a0.60501 (16)0.74508 (13)0.06851 (4)0.0202 (2)
C140.69151 (16)0.82815 (13)0.01168 (4)0.0221 (2)
H140.830 (2)0.8455 (17)0.0012 (5)0.029 (4)*
C14a0.63324 (16)0.85395 (13)0.05881 (4)0.0224 (2)
C150.41212 (19)0.67361 (17)0.25133 (5)0.0316 (3)
H15A0.335 (2)0.703 (2)0.2222 (6)0.041 (4)*
H15B0.448 (2)0.772 (2)0.2702 (6)0.037 (4)*
H15C0.345 (2)0.5992 (19)0.2696 (5)0.034 (4)*
C160.9879 (2)0.86329 (18)0.32026 (5)0.0329 (3)
H16A1.116 (3)0.8288 (19)0.3155 (6)0.038 (4)*
H16B0.975 (2)0.979 (2)0.3140 (6)0.040 (4)*
H16C0.964 (2)0.8394 (19)0.3533 (6)0.036 (4)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0291 (5)0.0389 (5)0.0192 (4)0.0000 (4)0.0033 (3)0.0036 (3)
O30.0323 (5)0.0336 (5)0.0179 (4)0.0008 (4)0.0010 (3)0.0003 (3)
O90.0258 (4)0.0217 (4)0.0232 (4)0.0035 (3)0.0017 (3)0.0039 (3)
O100.0285 (4)0.0328 (5)0.0176 (4)0.0071 (3)0.0013 (3)0.0003 (3)
N70.0213 (5)0.0226 (5)0.0183 (5)0.0030 (4)0.0010 (4)0.0002 (3)
C20.0319 (6)0.0309 (6)0.0183 (6)0.0032 (5)0.0025 (5)0.0002 (5)
C3a0.0294 (6)0.0218 (5)0.0168 (5)0.0033 (4)0.0016 (4)0.0027 (4)
C40.0227 (6)0.0273 (6)0.0232 (6)0.0005 (4)0.0026 (4)0.0031 (4)
C4a0.0223 (5)0.0226 (5)0.0213 (5)0.0017 (4)0.0008 (4)0.0027 (4)
C50.0204 (6)0.0376 (7)0.0236 (6)0.0033 (5)0.0011 (4)0.0004 (5)
C60.0264 (6)0.0295 (6)0.0237 (6)0.0084 (5)0.0017 (5)0.0009 (5)
C80.0298 (6)0.0208 (5)0.0209 (6)0.0037 (5)0.0016 (5)0.0010 (4)
C8a0.0194 (5)0.0183 (5)0.0214 (5)0.0022 (4)0.0004 (4)0.0000 (4)
C90.0199 (5)0.0174 (5)0.0222 (5)0.0015 (4)0.0014 (4)0.0024 (4)
C100.0215 (5)0.0220 (5)0.0180 (5)0.0026 (4)0.0002 (4)0.0004 (4)
C110.0187 (5)0.0261 (5)0.0241 (6)0.0022 (4)0.0022 (4)0.0007 (4)
C12a0.0179 (5)0.0236 (5)0.0217 (6)0.0030 (4)0.0011 (4)0.0008 (4)
C120.0185 (5)0.0292 (6)0.0238 (6)0.0024 (4)0.0018 (4)0.0036 (4)
C13b0.0220 (5)0.0189 (5)0.0196 (5)0.0024 (4)0.0004 (4)0.0021 (4)
C130.0194 (5)0.0271 (6)0.0201 (5)0.0000 (4)0.0028 (4)0.0007 (4)
C13a0.0206 (5)0.0203 (5)0.0196 (5)0.0032 (4)0.0022 (4)0.0012 (4)
C140.0212 (5)0.0239 (5)0.0205 (5)0.0018 (4)0.0002 (4)0.0016 (4)
C14a0.0251 (6)0.0207 (5)0.0217 (6)0.0026 (4)0.0045 (4)0.0012 (4)
C150.0261 (6)0.0363 (7)0.0332 (7)0.0043 (5)0.0073 (5)0.0021 (6)
C160.0314 (7)0.0443 (8)0.0217 (6)0.0082 (6)0.0026 (5)0.0043 (5)
Geometric parameters (Å, º) top
O1—C14a1.3800 (14)C8—C8a1.5071 (15)
O1—C21.4433 (14)C8—H8A0.990 (15)
O3—C3a1.3752 (14)C8—H8B0.976 (15)
O3—C21.4352 (15)C8a—C91.3842 (16)
O9—C91.3843 (13)C8a—C12a1.4082 (16)
O9—C151.4342 (15)C9—C101.4075 (15)
O10—C101.3710 (13)C10—C111.3900 (16)
O10—C161.4240 (15)C11—C121.3911 (17)
N7—C13a1.4062 (14)C11—H110.952 (15)
N7—C61.4605 (14)C12a—C121.3944 (16)
N7—C81.4621 (14)C12a—C131.4501 (15)
C2—H2A0.955 (15)C12—H120.953 (15)
C2—H2B0.995 (15)C13b—C141.4171 (16)
C3a—C41.3698 (17)C13b—C13a1.4821 (15)
C3a—C14a1.3891 (16)C13—C13a1.3613 (16)
C4—C4a1.4058 (16)C13—H130.966 (15)
C4—H41.008 (16)C14—C14a1.3683 (16)
C4a—C13b1.4020 (16)C14—H141.004 (15)
C4a—C51.5065 (16)C15—H15A0.966 (17)
C5—C61.5116 (17)C15—H15B0.991 (17)
C5—H5B1.034 (16)C15—H15C0.959 (16)
C5—H5A0.994 (16)C16—H16A0.959 (18)
C6—H6A1.004 (16)C16—H16B0.976 (18)
C6—H6B1.000 (15)C16—H16C0.990 (16)
C14a—O1—C2104.13 (9)O9—C9—C8a120.26 (10)
C3a—O3—C2104.44 (9)O9—C9—C10119.27 (10)
C9—O9—C15112.06 (9)C8a—C9—C10120.42 (10)
C10—O10—C16117.34 (9)O10—C10—C11125.34 (10)
C13a—N7—C6117.87 (9)O10—C10—C9115.20 (10)
C13a—N7—C8115.34 (9)C11—C10—C9119.46 (10)
C6—N7—C8112.91 (9)C10—C11—C12119.85 (10)
O3—C2—O1107.12 (9)C10—C11—H11120.7 (8)
O3—C2—H2A109.5 (8)C12—C11—H11119.5 (8)
O1—C2—H2A109.3 (8)C12—C12a—C8a118.61 (10)
O3—C2—H2B108.2 (8)C12—C12a—C13123.32 (10)
O1—C2—H2B108.9 (8)C8a—C12a—C13117.92 (10)
H2A—C2—H2B113.7 (12)C11—C12—C12a121.30 (11)
C4—C3a—O3128.62 (10)C11—C12—H12120.3 (8)
C4—C3a—C14a121.52 (10)C12a—C12—H12118.4 (8)
O3—C3a—C14a109.72 (10)C4a—C13b—C14119.68 (10)
C3a—C4—C4a117.53 (10)C4a—C13b—C13a120.21 (10)
C3a—C4—H4121.8 (9)C14—C13b—C13a120.10 (10)
C4a—C4—H4120.7 (9)C13a—C13—C12a121.22 (10)
C13b—C4a—C4121.35 (11)C13a—C13—H13121.1 (8)
C13b—C4a—C5118.50 (10)C12a—C13—H13116.8 (8)
C4—C4a—C5120.13 (10)C13—C13a—N7119.00 (10)
C4a—C5—C6110.04 (10)C13—C13a—C13b122.97 (10)
C4a—C5—H5B110.2 (9)N7—C13a—C13b117.79 (10)
C6—C5—H5B109.5 (8)C14a—C14—C13b117.67 (10)
C4a—C5—H5A111.6 (9)C14a—C14—H14119.9 (8)
C6—C5—H5A110.0 (9)C13b—C14—H14122.4 (8)
H5B—C5—H5A105.5 (12)C14—C14a—O1128.05 (11)
N7—C6—C5109.69 (10)C14—C14a—C3a122.24 (11)
N7—C6—H6A110.2 (9)O1—C14a—C3a109.58 (10)
C5—C6—H6A110.4 (9)O9—C15—H15A109.0 (10)
N7—C6—H6B107.1 (8)O9—C15—H15B110.1 (9)
C5—C6—H6B111.7 (9)H15A—C15—H15B109.5 (13)
H6A—C6—H6B107.7 (12)O9—C15—H15C106.3 (9)
N7—C8—C8a110.18 (9)H15A—C15—H15C111.7 (13)
N7—C8—H8A109.2 (8)H15B—C15—H15C110.3 (13)
C8a—C8—H8A110.5 (8)O10—C16—H16A112.3 (10)
N7—C8—H8B107.1 (8)O10—C16—H16B110.7 (10)
C8a—C8—H8B112.3 (8)H16A—C16—H16B109.6 (14)
H8A—C8—H8B107.5 (12)O10—C16—H16C104.6 (9)
C9—C8a—C12a120.31 (10)H16A—C16—H16C109.3 (13)
C9—C8a—C8122.77 (10)H16B—C16—H16C110.3 (13)
C12a—C8a—C8116.84 (10)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C2—H2A···O10i0.955 (15)2.407 (15)3.3031 (15)156.2 (11)
C2—H2B···N7ii0.995 (15)2.620 (15)3.5326 (17)152.5 (11)
Symmetry codes: (i) x, y+3/2, z1/2; (ii) x+1, y+2, z.

Experimental details

Crystal data
Chemical formulaC20H19NO4
Mr337.36
Crystal system, space groupMonoclinic, P21/c
Temperature (K)150
a, b, c (Å)6.9562 (15), 8.3067 (17), 28.343 (6)
β (°) 96.458 (3)
V3)1627.3 (6)
Z4
Radiation typeMo Kα
µ (mm1)0.10
Crystal size (mm)0.30 × 0.26 × 0.10
Data collection
DiffractometerBruker SMART APEX CCD area-detector
diffractometer
Absorption correctionMulti-scan
(SADABS; Sheldrick, 2009)
Tmin, Tmax0.850, 0.990
No. of measured, independent and
observed [I > 2σ(I)] reflections
24555, 3339, 3120
Rint0.037
(sin θ/λ)max1)0.625
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.041, 0.104, 1.06
No. of reflections3339
No. of parameters303
No. of restraints72
H-atom treatmentAll H-atom parameters refined
Δρmax, Δρmin (e Å3)0.26, 0.36

Computer programs: APEX2 (Bruker, 2010), SAINT (Bruker, 2009), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C2—H2A···O10i0.955 (15)2.407 (15)3.3031 (15)156.2 (11)
C2—H2B···N7ii0.995 (15)2.620 (15)3.5326 (17)152.5 (11)
Symmetry codes: (i) x, y+3/2, z1/2; (ii) x+1, y+2, z.
 

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