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The title compounds, C22H31NO3 and C20H27NO2, have similar conformations except in the molecular geometry and the bonding of two of the rings. These differences lead to marked differences in the biological activities of these compounds. Molecules of both compounds are linked by weak C—H...O hydrogen bonds in the crystal structures.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270104017457/ga1054sup1.cif
Contains datablocks global, II, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270104017457/ga1054Isup2.hkl
Contains datablock I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270104017457/ga1054IIsup3.hkl
Contains datablock II

CCDC references: 251326; 251327

Comment top

With the aim of studying anti-aromatase activity of some D-modified steroidal compounds, we have synthesized several new androstane derivatives (Penov-Gaši et al., 2001). Potent steroid aromatase inhibitors are mainly the A– and B-modified steroids, whereas the D-modified steroids (with the exception of testololactone) have received little research attention. Aromatase is a cytochrome P450 enzyme that catalyzes the conversion of androgens into estrogens at the last step of estrogen biosythesis (Thomson, 1974). Compounds that inhibit aromatase have potential applications in the treatment of advanced estrogen-dependent tumors, such as breast cancer, dometrial cancer, prostatic hyperplasia and prostate cancer. Within the framework of this project, we performed the structure analysis of the title compound, (I) and (II), respectively. The original basic crystallographic data have been deposited in the Cambridge Structural Database [CSD refcodes WULGAL, (I), and CCDC WULGEP, (II); Allen, 2002].

The structures of both compounds, deduced from chemical spectroscopic evidence, were confirmed by X-ray difraction analyses. Molecular-mechanics calculations (MMC) using PCMODEL (Serena Software, 1989) were also performed in order to define the conformation of the molecules in terms of energy minima. Since the starting materials were synthesized from the natural androstene derivative, the absolute stereochemistry of which is known (Fieser & Fieser, 1967), the X-ray structures are described for the appropriate enantiomer.

Perspective views of the molecules of (I) and (II) are shown in Figs. 1 and 2, respectively. The puckering (Cremer & Pople, 1975) and asymmetry parameters (Duax et al., 1976) reveal the following conformations. In (I), ring A has a 1α,4β-chair conformation, ring B has a 9α,8β-half-chair conformation and ring C adopts a 8β,12α-chair conformation. In (II), ring A exhibits a form intermediate between 1α-envelope and 1α,2β-half-chair, while rings B and C have 5α,8β- and 8β,12α-chair conformation, respectively.

The different conformations of rings A and B in (I) and (II), caused by the shifting of the double bond from C4=C5 in (I) to C5=C6 in (II), lead to significant differences in the steroid skeleton geometry in the region of rings A and B (Tables 1 and 3, and Fig. 3). Introducing the 4- and 5-double bonds into ring A of (I) and ring B of (II), respectively, also causes the twisting of the steroidal skeleton of each compound along the molecular principal axis, characterized by the values of the non-bonded C19—C10···C13—C18 torsion angles [5.7 (2) and 10.3 (2)° for (I) and (II), respectively]. The steroid geometries in the region of the C15 and C17 substituents (Fig.3) are similar. In the energy minimized models, this similarity is even more pronounced: ring A in (II) adopts an almost ideal 1E form, while the conformations of the other rings in (I) and (II) are not altered.

In the crystal packing of both compounds, molecules related by the screw axes are linked by weak hydrogen bonds, forming coils. In (I), C20—H20B···O2 bonds form coils along the c axis (Table 2); in (II), the C2—H2A···O2 and C20—H29B ···O1 bonds, in a `head-to-tail' and `tail-to-head' relationship, form coils along the b axis (Table 4).

The compounds were tested for possible anti-aromatase activity in the denucleated ovarian fractions from PMSG-pretreated female rats. For screening purposes, the compounds were tested in a single concentration (50 µM). The results showed that (I) exibited very low potency, while (II) completely inhibited aromatase activity in the presence of a subsaturated dose of testosterone, as well as in the presence of a saturated concentration (Penov-Gaši et al., 2001). The markedly greater biological activity of (II) can be interpreted as being due to the different molecular geometry in the region of rings A and B of the compounds, i.e. the presence of the 4-en-3-keto system instead of 5-en-3-acetoxy.

Experimental top

The preparation of (1) and (2) was described by Miljković at al. (1997). Treatment of (2) with acetic anhydride in pyridine (b) afforded the fragmentation product (I). By further treatment with sodium ethoxide in ethanol (c), compound (I) was transformed into 3β-hydroxy-17-methyl-17-oxo-16,17-seco-5-androstene-16-carbonitrile. Oppenauer oxidation of this compound using aluminium(III) tert-butoxide in cyclohexanone (d) gave (II) (Penov-Gaši et al., 2001). M.p. 398–401 K for (I) and 406–409 K for (II).

Refinement top

H atoms were placed in idealized positions? and treatd as riding, with Uiso(H) values fixed at 1.3Ueq of the parent atoms, or 1.5 Ueq for methyl H atoms.

Computing details top

For both compounds, data collection: CAD-4 Software (Enraf–Nonius, 1989); cell refinement: CAD-4 Software; data reduction: CAD-4 Software; program(s) used to solve structure: SHELXS86 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows, Version 1.074 (Farrugia, 1997); software used to prepare material for publication: CSU (Vicković, 1988).

Figures top
[Figure 1] Fig. 1. A perspective view of the molecule of (I), with the atomic labeling. Displacement ellipsoids are shown at the 30% probability level and H atoms are drawn as spheres of arbitrary radii.
[Figure 2] Fig. 2. A perspective view of the molecule of (II), with the atomic labeling. Displacement ellipsoids are shown at the 30% probability level and H atoms are drawn as spheres of arbitrary radii.
[Figure 3] Fig. 3. A superimposed fit for molecules of (I) (solid) and (II) (dashed) in the crystalline state, viewed perpendicular to the C8—C14 bond.
(I) 3β-acetoxy-17-methyl-17-oxo-16,17-seco-5-androstene-16-carbonitrile top
Crystal data top
C22H31NO3F(000) = 776
Mr = 357.48Dx = 1.194 Mg m3
Orthorhombic, P212121Cu Kα radiation, λ = 1.54180 Å
Hall symbol: P 2ac 2abCell parameters from 25 reflections
a = 5.946 (2) Åθ = 15.0–23.9°
b = 16.120 (2) ŵ = 0.62 mm1
c = 20.746 (3) ÅT = 293 K
V = 1988.5 (8) Å3Plate, colourless
Z = 40.20 × 0.18 × 0.04 mm
Data collection top
Enraf–Nonius CAD-4
diffractometer
Rint = 0.037
Radiation source: fine-focus sealed tubeθmax = 74.7°, θmin = 3.5°
Graphite monochromatorh = 67
ω/2θ scansk = 2020
6350 measured reflectionsl = 2525
2354 independent reflections3 standard reflections every 120 min
1621 reflections with I > 2σ(I) intensity decay: none
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.040H-atom parameters constrained
wR(F2) = 0.136 w = 1/[σ2(Fo2) + (0.0734P)2 + 0.1452P]
where P = (Fo2 + 2Fc2)/3
S = 0.99(Δ/σ)max = 0.035
2354 reflectionsΔρmax = 0.21 e Å3
240 parametersΔρmin = 0.17 e Å3
12 restraintsExtinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0015 (4)
Crystal data top
C22H31NO3V = 1988.5 (8) Å3
Mr = 357.48Z = 4
Orthorhombic, P212121Cu Kα radiation
a = 5.946 (2) ŵ = 0.62 mm1
b = 16.120 (2) ÅT = 293 K
c = 20.746 (3) Å0.20 × 0.18 × 0.04 mm
Data collection top
Enraf–Nonius CAD-4
diffractometer
Rint = 0.037
6350 measured reflections3 standard reflections every 120 min
2354 independent reflections intensity decay: none
1621 reflections with I > 2σ(I)
Refinement top
R[F2 > 2σ(F2)] = 0.04012 restraints
wR(F2) = 0.136H-atom parameters constrained
S = 0.99Δρmax = 0.21 e Å3
2354 reflectionsΔρmin = 0.17 e Å3
240 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
xyzUiso*/Ueq
C10.0163 (6)0.06363 (17)0.86123 (14)0.0554 (8)
H1A0.08820.01530.84240.072*
H1B0.14190.06150.84990.072*
C20.0379 (8)0.0586 (2)0.93461 (15)0.0635 (9)
H2A0.19540.05410.94630.082*
H2B0.03870.00930.95010.082*
C30.0619 (6)0.1341 (2)0.96606 (14)0.0573 (8)
H30.22450.13570.95840.075*
C40.0466 (7)0.2127 (2)0.94081 (14)0.0562 (8)
H4A0.20290.21430.95410.073*
H4B0.02870.26050.95920.073*
C50.0337 (6)0.21722 (17)0.86811 (13)0.0467 (7)
C60.0463 (6)0.28373 (19)0.83919 (15)0.0539 (7)
H60.10300.32570.86530.070*
C70.0538 (6)0.29735 (17)0.76779 (14)0.0547 (8)
H7A0.20840.29370.75320.071*
H7B0.00040.35270.75820.071*
C80.0883 (5)0.23420 (16)0.73111 (12)0.0417 (6)
H80.24700.24790.73800.054*
C90.0446 (5)0.14728 (16)0.75956 (12)0.0420 (6)
H90.11860.13900.75920.055*
C100.1206 (5)0.14242 (18)0.83103 (13)0.0436 (6)
C110.1461 (6)0.07858 (17)0.71803 (14)0.0550 (8)
H11A0.10020.02500.73480.072*
H11B0.30890.08160.72010.072*
C120.0703 (6)0.08662 (18)0.64824 (14)0.0525 (8)
H12A0.13290.04110.62340.068*
H12B0.09220.08230.64640.068*
C130.1431 (5)0.16902 (19)0.61770 (14)0.0438 (6)
C140.0400 (5)0.23978 (16)0.65810 (12)0.0423 (6)
H140.12330.23410.65360.055*
C150.0987 (6)0.32725 (18)0.63134 (14)0.0525 (8)
H15A0.02420.36470.64130.068*
H15B0.11010.32380.58480.068*
C160.3070 (7)0.3628 (2)0.65641 (16)0.0615 (9)
C170.0397 (6)0.1682 (2)0.54995 (14)0.0506 (7)
C180.4006 (5)0.1757 (2)0.61359 (18)0.0604 (9)
H18A0.46080.12530.59610.091*
H18B0.44060.22140.58620.091*
H18C0.46110.18470.65590.091*
C190.3782 (5)0.1382 (2)0.83789 (16)0.0621 (9)
H19A0.43140.08610.82140.093*
H19B0.44550.18270.81400.093*
H19C0.41850.14300.88250.093*
C200.1397 (8)0.1105 (2)0.50048 (15)0.0689 (10)
H20A0.30080.11300.50290.103*
H20B0.09040.05490.50880.103*
H20C0.09150.12710.45820.103*
C210.1570 (8)0.0878 (2)1.07213 (16)0.0669 (10)
C220.0830 (6)0.0871 (2)1.14097 (14)0.0755 (9)
H22A0.06310.06211.14410.113*
H22B0.07630.14301.15680.113*
H22C0.18850.05591.16620.113*
N0.4672 (7)0.3922 (2)0.67604 (17)0.0874 (11)
O10.0167 (4)0.13247 (15)1.03521 (10)0.0660 (7)
O20.3212 (7)0.0556 (2)1.05156 (14)0.1108 (13)
O30.1237 (4)0.20963 (15)0.53627 (11)0.0646 (6)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.066 (2)0.0453 (16)0.0547 (17)0.0029 (16)0.0003 (16)0.0098 (13)
C20.077 (2)0.0567 (19)0.0568 (17)0.002 (2)0.0016 (19)0.0154 (15)
C30.0612 (19)0.0642 (19)0.0466 (15)0.0069 (18)0.0023 (16)0.0101 (14)
C40.066 (2)0.0562 (18)0.0468 (15)0.0043 (18)0.0012 (17)0.0032 (13)
C50.0477 (16)0.0458 (14)0.0466 (14)0.0033 (14)0.0014 (14)0.0027 (13)
C60.0611 (18)0.0501 (16)0.0505 (15)0.0094 (16)0.0035 (16)0.0021 (13)
C70.068 (2)0.0449 (15)0.0508 (16)0.0156 (16)0.0014 (17)0.0008 (13)
C80.0424 (16)0.0409 (13)0.0418 (13)0.0016 (12)0.0021 (13)0.0011 (11)
C90.0399 (14)0.0385 (13)0.0475 (14)0.0008 (13)0.0002 (12)0.0031 (12)
C100.0384 (14)0.0452 (15)0.0472 (15)0.0000 (13)0.0029 (13)0.0077 (13)
C110.068 (2)0.0419 (15)0.0549 (17)0.0068 (17)0.0006 (17)0.0010 (13)
C120.059 (2)0.0431 (15)0.0559 (17)0.0012 (15)0.0000 (15)0.0040 (13)
C130.0379 (14)0.0457 (15)0.0478 (15)0.0015 (13)0.0014 (13)0.0008 (13)
C140.0397 (13)0.0423 (14)0.0450 (13)0.0028 (13)0.0030 (13)0.0023 (12)
C150.063 (2)0.0432 (15)0.0508 (16)0.0003 (15)0.0103 (16)0.0082 (13)
C160.080 (2)0.0503 (17)0.0540 (17)0.0119 (19)0.0015 (17)0.0090 (15)
C170.0477 (17)0.0515 (16)0.0525 (16)0.0044 (16)0.0004 (16)0.0017 (14)
C180.0439 (18)0.067 (2)0.070 (2)0.0041 (16)0.0042 (16)0.0018 (17)
C190.0429 (16)0.079 (2)0.0639 (19)0.0055 (18)0.0070 (15)0.0036 (19)
C200.085 (3)0.066 (2)0.0551 (17)0.006 (2)0.0092 (19)0.0121 (16)
C210.083 (3)0.061 (2)0.0572 (19)0.007 (2)0.009 (2)0.0110 (17)
C220.089 (3)0.077 (2)0.0565 (19)0.001 (2)0.008 (2)0.0133 (17)
N0.096 (3)0.073 (2)0.092 (2)0.033 (2)0.017 (2)0.0109 (18)
O10.0691 (15)0.0801 (15)0.0489 (11)0.0117 (14)0.0002 (11)0.0144 (11)
O20.128 (3)0.130 (3)0.0742 (18)0.074 (3)0.007 (2)0.0100 (17)
O30.0553 (13)0.0822 (16)0.0565 (13)0.0091 (14)0.0087 (11)0.0002 (12)
Geometric parameters (Å, º) top
C1—C21.530 (4)C12—C131.534 (4)
C1—C101.546 (4)C12—H12A0.9700
C1—H1A0.9700C12—H12B0.9700
C1—H1B0.9700C13—C171.534 (4)
C2—C31.503 (5)C13—C181.537 (4)
C2—H2A0.9700C13—C141.542 (4)
C2—H2B0.9700C14—C151.555 (4)
C3—O11.460 (4)C14—H140.9800
C3—C41.516 (4)C15—C161.460 (5)
C3—H30.9800C15—H15A0.9700
C4—C51.512 (4)C15—H15B0.9700
C4—H4A0.9700C16—N1.139 (5)
C4—H4B0.9700C17—O31.213 (4)
C5—C61.318 (4)C17—C201.506 (4)
C5—C101.521 (4)C18—H18A0.9600
C6—C71.498 (4)C18—H18B0.9600
C6—H60.9300C18—H18C0.9600
C7—C81.526 (4)C19—H19A0.9600
C7—H7A0.9700C19—H19B0.9600
C7—H7B0.9700C19—H19C0.9600
C8—C91.542 (4)C20—H20A0.9600
C8—C141.544 (4)C20—H20B0.9600
C8—H80.9800C20—H20C0.9600
C9—C111.527 (4)C21—O21.186 (5)
C9—C101.552 (4)C21—O11.342 (4)
C9—H90.9800C21—C221.494 (5)
C10—C191.540 (4)C22—H22A0.9600
C11—C121.522 (4)C22—H22B0.9600
C11—H11A0.9700C22—H22C0.9600
C11—H11B0.9700
C2—C1—C10114.4 (3)C9—C11—H11B109.4
C2—C1—H1A108.7H11A—C11—H11B108.0
C10—C1—H1A108.7C11—C12—C13112.5 (3)
C2—C1—H1B108.7C11—C12—H12A109.1
C10—C1—H1B108.7C13—C12—H12A109.1
H1A—C1—H1B107.6C11—C12—H12B109.1
C3—C2—C1110.8 (3)C13—C12—H12B109.1
C3—C2—H2A109.5H12A—C12—H12B107.8
C1—C2—H2A109.5C17—C13—C18110.4 (3)
C3—C2—H2B109.5C17—C13—C12104.9 (2)
C1—C2—H2B109.5C18—C13—C12111.4 (3)
H2A—C2—H2B108.1C17—C13—C14110.2 (2)
O1—C3—C2109.8 (3)C18—C13—C14112.0 (3)
O1—C3—C4106.0 (3)C12—C13—C14107.7 (2)
C2—C3—C4111.0 (3)C8—C14—C13114.6 (2)
O1—C3—H3110.0C8—C14—C15111.2 (2)
C2—C3—H3110.0C13—C14—C15112.8 (2)
C4—C3—H3110.0C8—C14—H14105.8
C5—C4—C3111.3 (3)C13—C14—H14105.8
C5—C4—H4A109.4C15—C14—H14105.8
C3—C4—H4A109.4C16—C15—C14114.8 (3)
C5—C4—H4B109.4C16—C15—H15A108.6
C3—C4—H4B109.4C14—C15—H15A108.6
H4A—C4—H4B108.0C16—C15—H15B108.6
C6—C5—C4120.8 (3)C14—C15—H15B108.6
C6—C5—C10122.5 (3)H15A—C15—H15B107.5
C4—C5—C10116.7 (3)O3—C17—C20119.8 (3)
C5—C6—C7125.5 (3)O3—C17—C13122.0 (3)
C5—C6—H6117.3C20—C17—C13118.2 (3)
C7—C6—H6117.3C13—C18—H18A109.5
C6—C7—C8112.3 (2)C13—C18—H18B109.5
C6—C7—H7A109.1H18A—C18—H18B109.5
C8—C7—H7A109.2C13—C18—H18C109.5
C6—C7—H7B109.1H18A—C18—H18C109.5
C8—C7—H7B109.1H18B—C18—H18C109.5
H7A—C7—H7B107.9C10—C19—H19A109.5
C7—C8—C9108.8 (2)C10—C19—H19B109.5
C7—C8—C14110.3 (2)H19A—C19—H19B109.5
C9—C8—C14113.4 (2)C10—C19—H19C109.5
C7—C8—H8108.1H19A—C19—H19C109.5
C9—C8—H8108.1H19B—C19—H19C109.5
C14—C8—H8108.1C17—C20—H20A109.5
C11—C9—C8112.1 (2)C17—C20—H20B109.5
C11—C9—C10112.8 (2)H20A—C20—H20B109.5
C8—C9—C10111.3 (2)C17—C20—H20C109.5
C11—C9—H9106.7H20A—C20—H20C109.5
C8—C9—H9106.7H20B—C20—H20C109.5
C10—C9—H9106.7O2—C21—O1122.8 (3)
C5—C10—C19109.1 (3)O2—C21—C22125.8 (4)
C5—C10—C1108.1 (2)O1—C21—C22111.4 (4)
C19—C10—C1109.0 (3)C21—C22—H22A109.5
C5—C10—C9110.1 (2)C21—C22—H22B109.5
C19—C10—C9112.3 (3)H22A—C22—H22B109.5
C1—C10—C9108.2 (2)C21—C22—H22C109.5
C12—C11—C9111.0 (2)H22A—C22—H22C109.5
C12—C11—H11A109.4H22B—C22—H22C109.5
C9—C11—H11A109.4C21—O1—C3117.1 (3)
C12—C11—H11B109.4
C10—C1—C2—C355.8 (4)C8—C9—C10—C1165.1 (3)
C1—C2—C3—O1173.5 (3)C8—C9—C11—C1252.5 (4)
C1—C2—C3—C456.6 (4)C10—C9—C11—C12179.0 (3)
O1—C3—C4—C5173.8 (3)C9—C11—C12—C1360.8 (4)
C2—C3—C4—C554.5 (4)C11—C12—C13—C17176.4 (3)
C2—C1—C10—C549.6 (4)C11—C12—C13—C1864.1 (4)
C3—C4—C5—C6128.5 (3)C11—C12—C13—C1459.0 (3)
C3—C4—C5—C1052.5 (4)C7—C8—C14—C13170.0 (2)
C4—C5—C6—C7175.9 (3)C9—C8—C14—C1347.7 (3)
C4—C5—C10—C148.5 (4)C7—C8—C14—C1560.7 (3)
C10—C5—C6—C73.1 (6)C9—C8—C14—C15177.0 (3)
C5—C6—C7—C812.6 (5)C17—C13—C14—C8166.2 (2)
C6—C7—C8—C944.1 (4)C18—C13—C14—C870.4 (3)
C6—C7—C8—C14169.1 (3)C12—C13—C14—C852.3 (3)
C7—C8—C9—C11169.5 (3)C17—C13—C14—C1565.2 (3)
C14—C8—C9—C1146.3 (3)C18—C13—C14—C1558.1 (4)
C7—C8—C9—C1063.2 (3)C12—C13—C14—C15179.1 (3)
C14—C8—C9—C10173.7 (2)C8—C14—C15—C1641.4 (4)
C6—C5—C10—C19109.2 (4)C13—C14—C15—C1688.9 (3)
C4—C5—C10—C1969.8 (4)C18—C13—C17—O3134.9 (3)
C6—C5—C10—C1132.5 (3)C12—C13—C17—O3104.9 (3)
C6—C5—C10—C914.5 (4)C14—C13—C17—O310.7 (4)
C4—C5—C10—C9166.5 (3)C18—C13—C17—C2048.1 (4)
C2—C1—C10—C1968.7 (4)C12—C13—C17—C2072.0 (3)
C2—C1—C10—C9168.9 (3)C14—C13—C17—C20172.3 (3)
C11—C9—C10—C5174.2 (2)O2—C21—O1—C35.5 (6)
C8—C9—C10—C547.2 (3)C22—C21—O1—C3176.4 (3)
C11—C9—C10—C1952.4 (4)C2—C3—O1—C2183.4 (4)
C8—C9—C10—C1974.6 (3)C4—C3—O1—C21156.5 (3)
C11—C9—C10—C167.9 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C20—H20B···O2i0.962.553.447 (5)155 (1)
Symmetry code: (i) x+1/2, y, z1/2.
(II) 17-methyl-3,17-dioxo-16,17-seco-4-androstene-16-carbonitrile top
Crystal data top
C20H27NO2F(000) = 680
Mr = 313.43Dx = 1.184 Mg m3
Orthorhombic, P212121Cu Kα radiation, λ = 1.54180 Å
Hall symbol: P 2ac 2abCell parameters from 25 reflections
a = 8.929 (2) Åθ = 25.0–29.6°
b = 10.022 (3) ŵ = 0.59 mm1
c = 19.651 (9) ÅT = 293 K
V = 1758.5 (10) Å3Plate, colourless
Z = 40.45 × 0.40 × 0.06 mm
Data collection top
Enraf–Nonius CAD-4
diffractometer
Rint = 0.054
Radiation source: fine-focus sealed tubeθmax = 74.6°, θmin = 4.5°
Graphite monochromatorh = 1111
ω/2θ scansk = 1212
4254 measured reflectionsl = 2424
2073 independent reflections3 standard reflections every 120 min
1723 reflections with I > 2σ(I) intensity decay: none
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.036H-atom parameters constrained
wR(F2) = 0.119 w = 1/[σ2(Fo2) + (0.0788P)2 + 0.1175P]
where P = (Fo2 + 2Fc2)/3
S = 0.91(Δ/σ)max = 0.001
2073 reflectionsΔρmax = 0.19 e Å3
212 parametersΔρmin = 0.14 e Å3
0 restraintsExtinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0033 (7)
Crystal data top
C20H27NO2V = 1758.5 (10) Å3
Mr = 313.43Z = 4
Orthorhombic, P212121Cu Kα radiation
a = 8.929 (2) ŵ = 0.59 mm1
b = 10.022 (3) ÅT = 293 K
c = 19.651 (9) Å0.45 × 0.40 × 0.06 mm
Data collection top
Enraf–Nonius CAD-4
diffractometer
Rint = 0.054
4254 measured reflections3 standard reflections every 120 min
2073 independent reflections intensity decay: none
1723 reflections with I > 2σ(I)
Refinement top
R[F2 > 2σ(F2)] = 0.0360 restraints
wR(F2) = 0.119H-atom parameters constrained
S = 0.91Δρmax = 0.19 e Å3
2073 reflectionsΔρmin = 0.14 e Å3
212 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
xyzUiso*/Ueq
C10.0812 (3)0.2346 (3)0.64725 (12)0.0667 (6)
H1A0.12760.15710.66800.087*
H1B0.12030.31320.66980.087*
C20.1252 (4)0.2395 (3)0.57196 (13)0.0856 (8)
H2A0.09920.15560.55040.111*
H2B0.23270.25130.56820.111*
C30.0476 (4)0.3511 (3)0.53601 (13)0.0821 (8)
C40.1013 (4)0.3845 (2)0.55939 (11)0.0714 (6)
H40.15470.44860.53530.093*
C50.1666 (3)0.3291 (2)0.61330 (10)0.0595 (5)
C60.3255 (3)0.3620 (3)0.63036 (12)0.0718 (7)
H6A0.36030.43320.60090.093*
H6B0.38800.28440.62240.093*
C70.3405 (3)0.4051 (2)0.70404 (11)0.0637 (5)
H7A0.28390.48650.71120.083*
H7B0.44480.42370.71400.083*
C80.2834 (2)0.29753 (18)0.75210 (9)0.0476 (4)
H80.34500.21750.74590.062*
C90.1199 (2)0.26172 (18)0.73536 (9)0.0448 (4)
H90.06070.34170.74540.058*
C100.0892 (2)0.22770 (19)0.65891 (9)0.0527 (5)
C110.0638 (2)0.1535 (2)0.78385 (10)0.0531 (5)
H11A0.04050.13420.77400.069*
H11B0.12090.07240.77660.069*
C120.0786 (2)0.1964 (2)0.85772 (10)0.0536 (5)
H12A0.04490.12420.88680.070*
H12B0.01370.27240.86570.070*
C130.2404 (2)0.2343 (2)0.87764 (9)0.0510 (4)
C140.2953 (2)0.34169 (19)0.82709 (10)0.0493 (4)
H140.22530.41650.83190.064*
C150.4515 (2)0.3986 (3)0.84610 (13)0.0660 (6)
H15A0.45960.48850.82820.086*
H15B0.45870.40420.89530.086*
C160.5777 (3)0.3199 (3)0.82072 (14)0.0708 (6)
C170.2251 (3)0.2965 (3)0.94898 (11)0.0647 (6)
C180.3404 (3)0.1097 (2)0.87870 (12)0.0660 (6)
H18A0.43760.13290.89590.099*
H18B0.35000.07510.83340.099*
H18C0.29600.04320.90750.099*
C190.1485 (3)0.0878 (2)0.63996 (12)0.0691 (6)
H19A0.09250.02120.66410.104*
H19B0.25240.08130.65210.104*
H19C0.13750.07400.59190.104*
C200.2661 (5)0.2190 (4)1.01053 (13)0.1002 (11)
H20A0.37010.19521.00840.150*
H20B0.20630.13951.01270.150*
H20C0.24830.27221.05040.150*
N0.6758 (3)0.2605 (3)0.79980 (15)0.0993 (8)
O10.1046 (4)0.4091 (3)0.48759 (11)0.1200 (9)
O20.1757 (3)0.4077 (2)0.95542 (10)0.1046 (8)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0609 (13)0.0730 (13)0.0663 (12)0.0055 (12)0.0120 (10)0.0069 (11)
C20.0888 (18)0.0935 (18)0.0746 (14)0.0004 (16)0.0267 (14)0.0161 (14)
C30.111 (2)0.0741 (15)0.0608 (13)0.0183 (16)0.0180 (14)0.0083 (11)
C40.0961 (18)0.0626 (12)0.0556 (10)0.0053 (13)0.0015 (12)0.0051 (10)
C50.0722 (13)0.0546 (11)0.0516 (10)0.0026 (11)0.0082 (10)0.0009 (8)
C60.0699 (14)0.0768 (15)0.0688 (12)0.0093 (13)0.0183 (12)0.0162 (11)
C70.0573 (11)0.0599 (12)0.0739 (13)0.0175 (11)0.0063 (11)0.0117 (10)
C80.0421 (8)0.0451 (9)0.0556 (10)0.0031 (7)0.0035 (7)0.0021 (8)
C90.0415 (8)0.0436 (8)0.0492 (9)0.0018 (7)0.0030 (7)0.0001 (7)
C100.0579 (11)0.0493 (10)0.0510 (9)0.0012 (9)0.0010 (9)0.0020 (8)
C110.0481 (9)0.0547 (10)0.0564 (10)0.0110 (9)0.0047 (8)0.0022 (8)
C120.0487 (10)0.0574 (10)0.0546 (10)0.0023 (9)0.0085 (9)0.0066 (8)
C130.0487 (9)0.0542 (10)0.0500 (9)0.0058 (9)0.0015 (8)0.0001 (8)
C140.0409 (8)0.0459 (9)0.0611 (10)0.0007 (8)0.0002 (8)0.0034 (8)
C150.0495 (11)0.0691 (12)0.0795 (14)0.0087 (11)0.0013 (10)0.0135 (11)
C160.0449 (11)0.0808 (15)0.0867 (15)0.0100 (12)0.0043 (11)0.0052 (13)
C170.0588 (12)0.0772 (14)0.0582 (11)0.0039 (11)0.0026 (10)0.0091 (11)
C180.0626 (13)0.0619 (12)0.0734 (13)0.0143 (11)0.0015 (11)0.0086 (10)
C190.0911 (17)0.0536 (11)0.0626 (11)0.0029 (13)0.0099 (12)0.0076 (10)
C200.135 (3)0.111 (2)0.0547 (12)0.006 (2)0.0067 (16)0.0020 (14)
N0.0518 (12)0.109 (2)0.137 (2)0.0030 (14)0.0143 (13)0.0068 (18)
O10.158 (2)0.1163 (17)0.0854 (13)0.0125 (19)0.0492 (16)0.0143 (13)
O20.143 (2)0.0963 (14)0.0742 (11)0.0417 (16)0.0095 (13)0.0290 (10)
Geometric parameters (Å, º) top
C1—C21.532 (3)C11—C121.520 (3)
C1—C101.541 (3)C11—H11A0.9700
C1—H1A0.9700C11—H11B0.9700
C1—H1B0.9700C12—C131.544 (3)
C2—C31.493 (5)C12—H12A0.9700
C2—H2A0.9700C12—H12B0.9700
C2—H2B0.9700C13—C181.535 (3)
C3—O11.226 (3)C13—C171.540 (3)
C3—C41.446 (5)C13—C141.544 (3)
C4—C51.331 (3)C14—C151.553 (3)
C4—H40.9300C14—H140.9800
C5—C61.495 (4)C15—C161.463 (3)
C5—C101.521 (3)C15—H15A0.9700
C6—C71.517 (4)C15—H15B0.9700
C6—H6A0.9700C16—N1.136 (4)
C6—H6B0.9700C17—O21.205 (3)
C7—C81.521 (3)C17—C201.483 (4)
C7—H7A0.9700C18—H18A0.9600
C7—H7B0.9700C18—H18B0.9600
C8—C141.542 (3)C18—H18C0.9600
C8—C91.539 (2)C19—H19A0.9600
C8—H80.9800C19—H19B0.9600
C9—C111.528 (3)C19—H19C0.9600
C9—C101.565 (3)C20—H20A0.9600
C9—H90.9800C20—H20B0.9600
C10—C191.544 (3)C20—H20C0.9600
C2—C1—C10113.5 (2)C12—C11—C9111.46 (17)
C2—C1—H1A108.9C12—C11—H11A109.3
C10—C1—H1A108.9C9—C11—H11A109.3
C2—C1—H1B108.9C12—C11—H11B109.3
C10—C1—H1B108.9C9—C11—H11B109.3
H1A—C1—H1B107.7H11A—C11—H11B108.0
C3—C2—C1111.3 (2)C11—C12—C13113.18 (16)
C3—C2—H2A109.4C11—C12—H12A108.9
C1—C2—H2A109.4C13—C12—H12A108.9
C3—C2—H2B109.4C11—C12—H12B108.9
C1—C2—H2B109.4C13—C12—H12B108.9
H2A—C2—H2B108.0H12A—C12—H12B107.8
O1—C3—C4121.2 (3)C18—C13—C17111.63 (17)
O1—C3—C2122.0 (3)C18—C13—C14113.04 (16)
C4—C3—C2116.7 (2)C17—C13—C14109.39 (17)
C5—C4—C3124.0 (3)C18—C13—C12110.30 (18)
C5—C4—H4118.0C17—C13—C12104.29 (16)
C3—C4—H4118.0C14—C13—C12107.76 (16)
C4—C5—C6120.2 (2)C8—C14—C13113.14 (15)
C4—C5—C10123.3 (2)C8—C14—C15113.38 (16)
C6—C5—C10116.50 (19)C13—C14—C15112.71 (18)
C5—C6—C7111.1 (2)C8—C14—H14105.6
C5—C6—H6A109.4C13—C14—H14105.6
C7—C6—H6A109.4C15—C14—H14105.6
C5—C6—H6B109.4C16—C15—C14114.33 (18)
C7—C6—H6B109.4C16—C15—H15A108.7
H6A—C6—H6B108.0C14—C15—H15A108.7
C6—C7—C8111.19 (18)C16—C15—H15B108.7
C6—C7—H7A109.4C14—C15—H15B108.7
C8—C7—H7A109.4H15A—C15—H15B107.6
C6—C7—H7B109.4O2—C17—C20119.3 (2)
C8—C7—H7B109.4O2—C17—C13120.2 (2)
H7A—C7—H7B108.0C20—C17—C13120.6 (2)
C7—C8—C14111.53 (16)C13—C18—H18A109.5
C7—C8—C9110.51 (16)C13—C18—H18B109.5
C14—C8—C9109.64 (14)H18A—C18—H18B109.5
C7—C8—H8108.4C13—C18—H18C109.5
C14—C8—H8108.4H18A—C18—H18C109.5
C9—C8—H8108.4H18B—C18—H18C109.5
C11—C9—C8110.08 (16)C10—C19—H19A109.5
C11—C9—C10112.75 (16)C10—C19—H19B109.5
C8—C9—C10114.96 (15)H19A—C19—H19B109.5
C11—C9—H9106.1C10—C19—H19C109.5
C8—C9—H9106.1H19A—C19—H19C109.5
C10—C9—H9106.1H19B—C19—H19C109.5
C5—C10—C1109.35 (19)C17—C20—H20A109.5
C5—C10—C19107.99 (17)C17—C20—H20B109.5
C1—C10—C19110.1 (2)H20A—C20—H20B109.5
C5—C10—C9109.92 (16)C17—C20—H20C109.5
C1—C10—C9107.81 (16)H20A—C20—H20C109.5
C19—C10—C9111.67 (17)H20B—C20—H20C109.5
C10—C1—C2—C354.3 (3)C8—C9—C10—C1163.94 (18)
C1—C2—C3—O1149.3 (3)C11—C9—C10—C1952.3 (2)
C1—C2—C3—C433.0 (4)C8—C9—C10—C1975.0 (2)
O1—C3—C4—C5177.0 (3)C8—C9—C11—C1256.8 (2)
C2—C3—C4—C55.2 (4)C10—C9—C11—C12173.38 (17)
C2—C1—C10—C545.5 (3)C9—C11—C12—C1356.9 (2)
C3—C4—C5—C6175.1 (2)C11—C12—C13—C1869.4 (2)
C3—C4—C5—C102.8 (4)C11—C12—C13—C17170.60 (17)
C4—C5—C6—C7128.2 (2)C11—C12—C13—C1454.4 (2)
C4—C5—C10—C117.6 (3)C7—C8—C14—C13179.19 (17)
C10—C5—C6—C753.8 (3)C9—C8—C14—C1358.1 (2)
C5—C6—C7—C857.7 (3)C7—C8—C14—C1549.2 (2)
C6—C7—C8—C956.6 (2)C9—C8—C14—C15171.97 (17)
C6—C7—C8—C14178.85 (19)C18—C13—C14—C866.7 (2)
C7—C8—C9—C11179.92 (17)C17—C13—C14—C8168.23 (17)
C14—C8—C9—C1156.8 (2)C12—C13—C14—C855.4 (2)
C7—C8—C9—C1051.3 (2)C18—C13—C14—C1563.6 (2)
C14—C8—C9—C10174.63 (16)C17—C13—C14—C1561.5 (2)
C6—C5—C10—C1164.4 (2)C12—C13—C14—C15174.28 (16)
C4—C5—C10—C19102.2 (3)C8—C14—C15—C1645.0 (3)
C6—C5—C10—C1975.8 (2)C13—C14—C15—C1685.1 (2)
C6—C5—C10—C946.3 (3)C18—C13—C17—O2165.6 (3)
C4—C5—C10—C9135.8 (2)C14—C13—C17—O239.7 (3)
C2—C1—C10—C1973.0 (3)C12—C13—C17—O275.3 (3)
C2—C1—C10—C9165.0 (2)C18—C13—C17—C2016.4 (3)
C11—C9—C10—C5172.11 (18)C14—C13—C17—C20142.3 (3)
C8—C9—C10—C544.8 (2)C12—C13—C17—C20102.7 (3)
C11—C9—C10—C168.8 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C2—H2A···O2i0.972.583.402 (4)142 (1)
C20—H20B···O1i0.962.493.422 (4)167 (1)
Symmetry code: (i) x, y1/2, z+3/2.

Experimental details

(I)(II)
Crystal data
Chemical formulaC22H31NO3C20H27NO2
Mr357.48313.43
Crystal system, space groupOrthorhombic, P212121Orthorhombic, P212121
Temperature (K)293293
a, b, c (Å)5.946 (2), 16.120 (2), 20.746 (3)8.929 (2), 10.022 (3), 19.651 (9)
V3)1988.5 (8)1758.5 (10)
Z44
Radiation typeCu KαCu Kα
µ (mm1)0.620.59
Crystal size (mm)0.20 × 0.18 × 0.040.45 × 0.40 × 0.06
Data collection
DiffractometerEnraf–Nonius CAD-4
diffractometer
Enraf–Nonius CAD-4
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
6350, 2354, 1621 4254, 2073, 1723
Rint0.0370.054
(sin θ/λ)max1)0.6250.625
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.040, 0.136, 0.99 0.036, 0.119, 0.91
No. of reflections23542073
No. of parameters240212
No. of restraints120
H-atom treatmentH-atom parameters constrainedH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.21, 0.170.19, 0.14

Computer programs: CAD-4 Software (Enraf–Nonius, 1989), CAD-4 Software, SHELXS86 (Sheldrick, 1990), SHELXL97 (Sheldrick, 1997), ORTEP-3 for Windows, Version 1.074 (Farrugia, 1997), CSU (Vicković, 1988).

Selected torsion angles (º) for (I) top
C10—C1—C2—C355.8 (4)C10—C5—C6—C73.1 (6)
C1—C2—C3—C456.6 (4)C5—C6—C7—C812.6 (5)
C2—C3—C4—C554.5 (4)C6—C7—C8—C944.1 (4)
C2—C1—C10—C549.6 (4)C7—C8—C9—C1063.2 (3)
C3—C4—C5—C1052.5 (4)C6—C5—C10—C914.5 (4)
C4—C5—C10—C148.5 (4)C8—C9—C10—C547.2 (3)
Hydrogen-bond geometry (Å, º) for (I) top
D—H···AD—HH···AD···AD—H···A
C20—H20B···O2i0.9602.5533.447 (5)154.9 (2)
Symmetry code: (i) x+1/2, y, z1/2.
Selected torsion angles (º) for (II) top
C10—C1—C2—C354.3 (3)C10—C5—C6—C753.8 (3)
C1—C2—C3—C433.0 (4)C5—C6—C7—C857.7 (3)
C2—C3—C4—C55.2 (4)C6—C7—C8—C956.6 (2)
C2—C1—C10—C545.5 (3)C7—C8—C9—C1051.3 (2)
C3—C4—C5—C102.8 (4)C6—C5—C10—C946.3 (3)
C4—C5—C10—C117.6 (3)C8—C9—C10—C544.8 (2)
Hydrogen-bond geometry (Å, º) for (II) top
D—H···AD—HH···AD···AD—H···A
C2—H2A···O2i0.9702.5833.402 (4)142.3 (2)
C20—H20B···O1i0.9602.4863.422 (4)167.4 (2)
Symmetry code: (i) x, y1/2, z+3/2.
 

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