9 A orange crystal (0.086 × 0.150 × 0.240)
mm³ of compound 9 was
selected for X-ray diffraction. Intensity data were collected at
r.t. (T = 298K) using a diffractometer
Kappa CCD of Enraf Nonius with MoKα monochromatic radiation (λ = 0.71073 Å)
and using the Collect¹0a software, as well as Scalepack¹0b for
cell refinement. The compound 9 was measured
a total of 4349 reflections to a maximum 2θ of 27.42˚.
No significant absorption effect (µ = 0.088
mm-¹) for compound 9 was
revealed, so no absorption correction was applied. The crystal structure
for compound 9 was solved by direct methods
and refined anisotropically with full matrix least square on F² using
SHELXL-97 program.¹0c H atoms attached to C
atoms were located on stereochemical grounds placed (C-H = 0.93-0.98 Å)
and refined as riding with Uiso(H) = 1.5
Ueq (C-methyl) or 1.2 Ueq(other) times the value
of the equivalent isotropic displacement parameter of atoms to which
they are bonded. The software used were: data collection: COLLECT;¹0a cell
refinement: HKL SCALEPACK;¹0b data reduction:
HKL DENZO and SCALEPACK.¹0b The program (s)used
to solve structure: SHELXS-97.¹0d The program
(s)used to refine structure: SHELXL-97.¹0c molecular
graphics: ORTEP-3, software used to prepare material for publication:
WinGX.¹0e Crystallographic data for compounds 9 have been deposited with the Cambridge
Crystallographic Data Center as Supplementary Publication No. CCDC
739857. Copies of the data can be obtained, free of charge, on application
to CCDC, 12 Union Road, Cambridge CH21EZ, UK (fax:+44 1223
336 033 or e-mail: deposit@ccdc.cam.ac.uk).
11
Crystal Data and
Structure Refinement for Compound 9
Empirical formula:
C28H24N2O3; formula
weight: 436.49; temperature: 295 (2) K; wavelength: 0.71073 Å;
crystal system: monoclinic; space group: Pn; unit cell dimensions: a = 5.32360
(10) Å, b = 9.9426
(3) Å, β = 95.6930
(10)˚, c = 20.1385
(7) Å; volume: 1060.68 (5) ų; Z: 2; density(calcd): 1.367 mg/m³;
absorption coefficient: 0.088 mm-¹; F(000): 460; crystal size: (0.086 × 0.150 × 0.240) mm³; θ range
for data collection: 2.29-27.42˚; index ranges: -6 £ h £ 6, -12 £ k £ 11, -26£ l £ 25;
reflections collected: 4349; independent reflections: 4219 [R(int) = 0.060]; completeness
to θ = 27.42˚: 98.7%;
absorption correction: none; refinement method: full-matrix least-squares
on F²; data/restraints/parameters:
4219/2/365; goodness-of-fit on F²:
1.077; final R indices [I > 2σ(I)]: R1 = 0.0562, wR2 = 0.1403; R indices (all data): R1 = 0.0803, wR2 = 0.1662;
largest diff. peak and hole: 0.305 and -0.343 e Å-³.
12 Melting points were obtained on Thomas
Hoover and are uncorrected. Analytical grade solvents were used.
Column chromatography was performed on silica gel (Acros Organics
0.035-0.070 mm, pore diameter ca 6 nm). Infrared spectra
were recorded on a Perkin-Elmer FT-IR spectrometer. ¹H
and ¹³C NMR were recorded at r.t. using
a Varian Gemini 200, in the solvents indicated, with TMS as internal
standard. Chemical shifts (δ) are given in ppm. Electron-impact
mass spectra (70 eV) were obtained using a VG Autospec apparatus
(Micromass, Manchester, UK). The main fragments were described as
a relation between atomic mass units and the charge (m/e) and the relative abundance in
percentage of the base peak intensity. Lapachol(1)
was extracted from the hardwood Tabebuia sp. (Tecoma) and purified by a series of recrystallizations
with the appropriate solvent.¹³a β-lapachone
(2) was obtained by acid cyclization from
lapachol (1) by Hooker’s methodology.¹³b
General Procedure for the Synthesis of
the Compounds 8-10
To 1.0 mmol of β-lapachone
(2) or nor-β-lapachone (3) in a solution of glacial AcOH (10.0
mL), was added NH4OAc (14.4 mmol), followed by reflux
for 2.5 h. After cooling, the reaction medium was poured in H2O,
and the solid residue was filtered under vacuum, washed with water
for neutralization and soon after the solid was chromatographed in
a silica gel column starting with hexane as eluent. In preparing 8, the compound was found in a polarity corresponding
to 2.5% of the EtOAc-hexane gradient. In obtention
of 9, the compound was chromatographed
in the EtOAc-hexane gradient corresponding to 3.5%.
Compound 10 was obtained in the EtOAc-hexane
gradient corresponding to 3.5%. The orange solids were recrystallized
in a mixture of hexane-acetone (1:1).
Spectroscopic Data of Compound 8
Orange
crystals; mp 244-245 ˚C; yield 11.2%.
IR (KBr): 3064, 2963, 2924, 2851, 1665, 1629, 1499, 1388, 1284, 1172,
1074, 1062, 1020, 870, 759, 703 cm-¹. ¹H
NMR (200 MHz, CDCl3): δ = 9.4
(dd, 1 H), 8.8 (dd, 1 H), 8.1 (dd, 2 H), 7.6 (m, 4 H), 3.8 (s, 2
H), 3.3 (s, 2 H), 1.6 (s, 12 H). ¹³C
NMR (50 MHz, CDCl3): δ = 160.8,
159.5, 153.6, 144.2, 133.5, 131.3, 129.0, 127.2, 126.4, 125.7, 125.3,
123.2, 122.7, 122.2, 120.1, 108.4, 107.4, 86.2, 85.7, 47.7, 45.1,
29.6, 28.4, 28.2. UV (EtOH): λmax (log ε) = 373.0
(4.09), 328.5 (4.29), 315.5 (4.27), 264.5 (4.36), 228.0 (4.49),
205.5 (4.40) nm. MS (70 eV): m/z (%) = 437
(33), 436 (100), 421 (15), 393 (8,0), 341 (8,0), 325 (20), 297 (6),
218 (5).
Spectroscopic Data of Compound
9
Orange crystals; mp 265-268 ˚C;
yield 11.2 (%). IR (KBr): 3074, 3058, 2976, 2928, 2856,
1663, 1630, 1601, 1531, 1460, 1385, 1276, 1250, 1117, 1069, 867,
752, 710 cm-¹. ¹H NMR
(200 MHz, CDCl3): δ = 9.3
(dd, 1 H), 8.4 (dd, 1 H), 8.1 (m, 2 H), 7.6 (m, 4 H), 3.6 (s, 2
H), 3.4 (s, 2 H), 1.6 (s, 12 H). ¹³C
NMR (50 MHz, CDCl3): δ = 161.3,
158.8, 154.5, 148.8, 139.7, 131.4, 131.0, 129.6, 128.2, 127.2, 126.6, 125.0,
124.0, 123.2, 122.5, 120.3, 109.7, 108.1, 88.3, 86.0, 45.3, 41.8,
28.4, 28.2. UV (EtOH): λmax (log ε) = 373.0 (3.99),
328.5 (4.19), 315.5 (1.32), 265.0 (1.62), 228.5 (2.21), 203.0 (2.03)
nm. MS (70 eV): m/z (%) = 436
(100), 421 (34), 393 (10,6), 341 (8.7), 325 (42), 297 (10), 218
(9), 140 (11), 41 (22).
Spectroscopic
Data of Compound 10
Orange crystals; mp 243-245 ˚C;
yield 10%. IR (KBr): 3094, 2973, 2920, 2850, 1667, 1611,
1597, 1584, 1529, 1459, 1446, 1365, 1348, 1316, 1282, 1255, 1158,
1117, 1087, 760, 720, 701 cm-¹. ¹H
NMR (200 MHz, CDCl3): δ = 9.0
(d, 1 H), 8.3 (d, 1 H), 8.1 (m, 2 H), 7.6 (m, 4 H), 3.3 (t, 2 H),
3.1 (t, 2 H), 2.0 (m, 4 H), 1.6 (s, 12 H). ¹³C
NMR (50 MHz, CDCl3): δ = 168.2,
155.2, 147.8, 147.2, 141.5, 130.7, 129.6, 129.6, 126.5, 125.8, 125.4,
125.0, 123.9, 123.0, 122.8, 121.7, 121.3, 109.5, 106.9, 76.8, 74.7,
32.2, 31.7, 26.6, 26.3, 22.8, 18.4. UV (EtOH): λmax (log ε) = 364
(4.01), 306 (4.62), 230 (4.67) nm. MS (70 eV): m/z (%) = 464
(5), 408 (2), 352 (2), 44 (13), 40 (100).
