New Bioactive 2,3-Epoxycyclohexenes and Isocoumarins
7.5, 3.5 Hz, 1 H, 5-H), 3.50 (ddd, J = 3.5, 1.5, 1.0 Hz, 1 H, 7a-H),
botryum violaceum and the alga Chlorella fusca (both on MPY me-
3.44 (dd, J = 3.5, 1.5 Hz, 1 H, 1a-H), 1.63 (m, 1 H, 8a-H), 1.55 dium). The radius of zone of inhibition was measured in mm.
(m, 1 H, 8b-H), 1.40 (m, 2 H, 9-H), 0.97 (t, J = 7.3 Hz, 3 H, 10-
Computational Section: DFT calculations were performed with
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 133.4 (C-6a), 132.0 (C-
Spartan’06 (Wavefunction Inc., Irvine CA) by using standard pa-
2a), 89.3 (C-6), 75.2 (C-3), 73.3 (C-5), 63.0 (C-2), 60.3 (C-7), 54.9
rameters and convergence criteria. Geometry optimizations were
(C-7a), 54.3 (C-1a), 33.5 (C-8), 18.7 (C-9), 13.0 (C-10) ppm. IR
run at B3LYP/6-31G(d) level. Lowest-energy DFT structures for 1a
(CHCl ): ν
= 3460, 2940, 1250, 1130 cm–1. CI-MS (CH4): m/z
˜
3
max
and for its cis isomer were used for J-coupling estimations executed
with the Mestre-J program (MestreLab Research, Santiago de
Compostela) by using the Haasnoot-de Leeuw-Altona equation for
= 243.1 [M + 1]. EI-MS: m/z (%) = 242, (5), 224 (5), 204 (8), 187.1
(20), 170 (100), 170 (90), 151 (85), 123 (90), 124 (80), 109 (46), 81
(55).
chemical groups.[33] Predicted J1a-H/2-H and J7-aH/7-H values were
ca. 1 Hz for 1a, and ca. 3.5 Hz for its cis,cis isomer. TDDFT-CD
calculations were performed with Gaussian’03W, Revision D.01
(Gaussian, Inc., Pittsburgh PA) by using various functionals
(B3LYP, BH&HLYP) and basis sets (TZVP, ADZP)[34] for 1a (all
the functionals/basis sets combinations giving consistent results),
and B3LYP/TZVP for other compounds. CD spectra were gener-
ated as sums of Gaussians with 1500 or 2000 cm–1 half-height
widths by using dipole-velocity-computed rotational strengths. Di-
pole-length-computed values differed from dipole-velocity-com-
puted ones by less than 10% for all relevant bands for all com-
pounds. The latter ones always had energies well below the esti-
mated ionizations potentials and involved virtual orbitals with
negative eigenvalues.[35]
3
3
Phomolactone A (4): White solid; m.p. 187 °C. [α]2D0 = –58.1 (c =
0.92, CHCl3). CD {MeCN, λ [nm] (∆ε), c = 3.89ϫ10–4}: 262
(–5.84), 235 (–2.35), 214 (1.78), 196 (–4.61). H NMR (500 MHz,
1
CDCl3): δ = 10.66 (s, 1 H, OH), 6.49 (s, 1 H, 7-H), 4.55 (m, 1 H,
3-H), 3.20 (dd, J = 17.0, 3.5 Hz, 1 H, 4a-H), 2.73 (dd, J = 17.0,
11.0 Hz, 1 H, 4b-H), 1.90 (m, 1 H, 9a-H), 1.75 (m, 1 H, 9b-H),
1.60 (m, 2 H, 10-H), 0.98 (t, J = 7.3 Hz, 3 H, 11-H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 169.3 (C-1), 155.7 (C-8), 140.2 (C-
5), 128.0 (C-4a), 125.2 (C-6), 115.6 (C-7), 107.8 (C-8a), 79.2 (C-3),
36.8 (C-9), 27.2 (C-4), 18.1 (C-10), 13.7 (C-11) ppm. IR (CHCl3):
ν
= 3460, 2940, 1657 (C=O), 1624 (Ar), 1250, 1130 cm–1. UV
˜
max
(CHCl3): λmax = 260 (3.21), 315 (3.11) nm. EI-MS: m/z (%) = 256
(43) [M+ (35Cl)]+, 258 (13) [M (37Cl)]+, 215 (10), 212 (36) [M+
–
CO2], 172 (75), 171 (100), 69 (15). HREIMS: m/z = 256.0511
(calcd. 256.0502 for C12H13ClO4).
Supporting Information (see footnote on the first page of this arti-
cle): Supporting Information with 1H and 13C NMR spectra of
compounds 1a, 2–5.
Phomolactone B (5): White solid; m.p. 181–182 °C. [α]2D0 = –51.1 (c
= 0.85, CHCl3 + CD3OD). CD {MeCN, λ [nm] (∆ε), c =
8.99ϫ10–4}: 258 (–2.08), 236 (–0.53), 223 (0.31), 198 (–2.21). 1H
NMR (500 MHz, CDCl3 + CD3OD): δ = 6.93 (d, J = 8.5 Hz, 1 H,
6-H), 6.65 (d, J = 8.5 Hz, 1 H, 7-H), 4.48 (m, 1 H, 3-H), 3.06 (dd,
J = 17.0, 3.5 Hz, 1 H, 4a-H), 2.58 (dd, J = 17.0, 11.0 Hz, 1 H, 4b-
H), 1.80 (m, 1 H, 9a-H), 1.65 (m, 1 H, 9b-H), 1.45 (m, 2 H, 10-H),
0.90 (t, J = 7.3 Hz, 3 H, 11-H) ppm. 13C NMR (125 MHz, CDCl3
+ CD3OD): δ = 170.3 (C-1), 155.0 (C-8), 145.2 (C-5), 124.3 (C-4a),
123.9 (C-6), 115.4 (C-7), 108.2 (C-8a), 79.6 (C-3), 36.8 (C-9), 26.6
Acknowledgments
K. K., H. H., B. S. and S. D. thank the BASF AG and the Bundes-
ministerium für Bildung und Forschung (BMBF) (project no.
03F0360A); S. A. and T. K. thank the Hungarian Scientific Re-
search Fund (OTKA) and the National Office for Research and
Technology (NKTH) for financial support (T-049436, NI-61336
and K-68429). We are grateful to Qunxiu Hu for excellent technical
assistance.
(C-4), 18.0 (C-10), 13.6 (C-11) ppm. IR (CDCl + CD OD): ν
˜
max
3
3
= 3450, 2935, 1660 (C=O), 1620 (Ar), 1250, 1125 cm–1. UV (CDCl3
+ CD3OD): λmax = 260 (3.00), 315 (3.32) nm. EI-MS: m/z (%) =
222.1 (45), 204 (31) [M+ – H2O]+, 178 (33) [M+ – CO2], 171 (100), [1] K. Krohn, M. H. Sohrab, T. van Ree, S. Draeger, B. Schulz, S.
Antus, T. Kurtán, Eur. J. Org. Chem. 2008, accepted.
[2] V. Rukachaisirikul, U. Sommart, S. Phongpaichit, J. Sakayaroj,
K. Kirtikara, Phytochemistry 2008, 69, 783–787.
[3] M. Isaka, A. Jaturapat, K. Rukseree, K. Danwisetkanjana, M.
Tantichareon, Y. Thebtaranonth, J. Nat. Prod. 2001, 64, 1015–
1018.
[4] K. Krohn, A. Michel, E. Roemer, U. Flörke, H.-J. Aust, S.
Draeger, B. Schulz, V. Wray, Nat. Prod. Lett. 1995, 9, 309–314.
[5] J. Dai, K. Krohn, U. Flörke, D. Gehle, H.-J. Aust, S. Draeger,
B. Schulz, K. Rheinheimer, Eur. J. Org. Chem. 2005, 5100–
5105.
69 (12). HREIMS: m/z = 222.0881 (calcd. 222.0892 for C12H14O4).
Phomolactone C (6): White solid; m.p. 172 °C. [α]2D0 = –47.1 (c =
0.76, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 10.66 (s, 1 H, OH),
6.98 (d, J = 8.5 Hz, 1 H, 5-H), 6.79 (dd, J = 8.5, 0.5 Hz, 1 H, 6-
H), 4.56 (m, 1 H, 3-H), 3.13 (dd, J = 17.0, 3.5 Hz, 1 H, 4a-H), 2.70
(ddd, J = 17.0, 11.0, 0.5 Hz, 1 H, 4b-H), 1.90 (m, 1 H, 9a-H), 1.72
(m, 1 H, 9b-H), 1.60 (m, 2 H, 10-H), 0.98 (t, J = 7.3 Hz, 3 H, 11-
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 169.3 (C-1), 146.2 (C-
8), 143.5 (C-7), 124.5 (C-4a), 124.0 (C-6), 116.0 (C-5), 107.2 (C-
8a), 79.3 (C-3), 36.9 (C-9), 26.7 (C-4), 18.1 (C-10), 13.7 (C-11) ppm.
[6] W. S. Horn, M. S. J. Simmonds, R. E. Schwartz, W. M. Blaney,
Tetrahedron 1995, 51, 3969–3978.
IR (CDCl ): ν
= 3480, 2950, 1655 (C=O), 1620 (Ar), 1250,
˜
3
max
1125 cm–1. UV (CDCl3): λmax = 260 (2.90), 315 (3.22) nm. EI-MS:
m/z (%) = 222.1 (43), 204 (32) [M+ – H2O]+, 178 (30) [M+ – CO2],
171 (100), 69 (14). HREIMS: m/z = 222.0881 (calcd. 222.0892 for
C12H14O4).
[7] Y. Izawa, T. Shimizu, K. Koyama, S. Natori, Tetrahedron 1989,
45, 2323–2335.
[8] Y. S. Tsantrizos, K. K. Ogilvie, A. K. Watson, Can. J. Chem.
1992, 70, 2276–2284.
[9] C. C. J. Culvenor, J. A. Edgar, W. F. O. Marasa, M. F. Mackay,
C. P. Gorst-Allman, P. S. Steyn, R. Vleggaar, P. L. Wessela, Tet-
rahedron 1989, 45, 2351–2372.
Bioactivity Tests. Agar Diffusion Test: The tested compounds were
dissolved in acetone at a concentration of 1 mg/mL. 50 µL of the
solution was pipetted onto a sterile filter disc (50 µg/disc), which
was placed onto an appropriate agar growth medium for the respec-
tive test organism and subsequently sprayed with a suspension of
the test organism.[32] The test organisms were the Gram-positive
bacterium Bacillus megaterium (NB medium), the fungus Micro-
[10] G. A. Strobel, B. Daisy, U. Castillo, J. Harper, J. Nat. Prod.
2004, 67, 257–268.
[11] F. Koizumi, Y. Matsuda, S. Nakanishi, J. Antibiot. 2003, 56,
464–469.
[12] F. Koizumi, H. Ishiguro, K. Ando, H. Kondo, M. Yoshida, Y.
Matsuda, S. Nakanishi, J. Antibiot. 2003, 56, 603–609.
Eur. J. Org. Chem. 2009, 749–756
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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