7286
O. Geiseler, J. Podlech / Tetrahedron 68 (2012) 7280e7287
dehydroxylarone (8) and Z-8 [42.2 mg, 192
mmol, 70%, (2E,4E)/
CH), 6.24 (s, 1H, CH), 7.00 (s, 1H, CH). 13C NMR (100 MHz, CDCl3):
(2E,4Z)¼7:3] as a yellow solid. Separation of the isomers was ach-
ieved by column chromatography (silica gel, hexanes/EtOAc, 10:1)
yielding the pure natural product 8 and a mixture of isomers.
d
¼8.8 (CH3), 14.2 (CH3), 19.0 (CH3), 28.3 [C(CH3)3], 56.2 (OCH3), 80.4
(C), 93.9 (CH), 103.5 (C), 122.3 (CH), 128.1 (C), 134.7 (CH), 150.5 (C),
159.1 (C), 164.6 (C), 165.4 (C), 165.9 (C). MS (EI): m/z (%)¼320 (16)
Compound 8: IR (ATR): v 2923 cmꢂ1, 2854, 1678, 1622, 1585, 1546,
[Mþ], 253 (40), 219 (51), 208 (90),149 (38),125 (69), 57 (100). HRMS
~
1H2416O5þꢁ, EI): calcd 320.1624 amu, found 320.1621 amu.
12
1439, 1383, 1357, 1244, 1176, 1155, 1133, 1038, 1009, 974, 955, 914,
(½
C
18
883, 806, 745, 722, 694, 621, 540, 519, 464, 423. 1H NMR (400 MHz,
(E,Z)-35: IR (ATR): v 2976 cmꢂ1, 2927, 2865, 1689, 1630, 1551, 1458,
1381, 1335, 1294, 1248, 1161, 1135, 1012, 969, 940, 903, 855, 800,
773, 750, 682, 645, 559, 469, 405. 1H NMR (400 MHz, CDCl3):
~
CDCl3):
d
¼1.88 (d, J¼6.8 Hz, 3H, CH3), 1.94 (s, 3H, CH3), 1.96 (s, 3H,
CH3), 3.90 (s, 3H, OCH3), 6.04e6.14 (m, 1H, CH), 6.12 (s, 1H, CH), 6.41
(dq, J¼1.7, 11.3 Hz, 1H, CH), 7.12 (d, J¼11.3 Hz, 1H, CH). 13C NMR
d
¼1.42 (s, 9H, C(CH3)3), 1.89 (d, J¼1.1 Hz, 3H, CH3), 1.95 (s, 3H, CH3),
1.98 (s, 3H, CH3), 3.91 (s, 3H, OCH3), 5.78 (q, J¼1.1 Hz, 1H, CH), 6.23
(s, 1H, CH), 7.26 (s, 1H, CH). 13C NMR (100 MHz, CDCl3):
(100 MHz, CDCl3):
d
¼8.7 (CH3), 12.5 (CH3), 19.0 (CH3), 56.0 (CH3),
92.1 (CH), 102.1 (C), 123.2 (C), 127.4 (CH), 132.1 (CH), 136.6 (CH),
d
¼8.7 (CH3),
160.0 (C), 165.0 (C), 165.9 (C). MS (EI): m/z (%)¼220 (100) [Mþ], 205
13.9 (CH3), 24.4 (CH3), 28.1 (3ꢃ CH3), 56.1 (CH3), 80.0 (C), 93.1 (CH),
12
(24), 177 (22), 149 (19), 133 (33), 93 (29). HRMS (½
C
1H1616O3þꢁ,
103.0 (C), 121.8 (CH), 127.3 (C), 132.1 (CH), 149.5 (C), 159.3 (C), 164.7
13
EI): calcd 220.1099 amu, found 220.1102 amu. The spectroscopic
(C), 164.9 (C), 165.5 (C). MS (EI): m/z (%)¼320 (5) [Mþ], 264 (100),
data are in full agreement with published data.11
219 (43), 182 (10), 139 (23). HRMS (½
C
18
1H2416O5þꢁ, EI): calcd
12
320.1624 amu, found 320.1623 amu.
6.7. Infectoyprone (1)
6.7.3. (E,E)-5-(4-Methoxy-3-methyl-2-oxo-2H-pyran-6-yl)-3-
6.7.1. Ethyl (E,E)-5-(4-methoxy-3-methyl-2-oxo-2H-pyran-6-yl)-3-
methylhexa-2,4-dienoic acid (1, infectopyrone). Infectopyrone tert-
methylhexa-2,4-dienoate (33, infectopyrone ethyl ester). A soln of
butyl ester [(E,E)-35, 12.2 mg, 38
mmol] was treated for 30 min with
triethyl phosphonoacetate (32, 21.0 mg, 94
mmol) in anhydrous
F3CCO2H (500 L) in CH2Cl2 (2 mL). The solvent was removed under
m
dimethoxy ethane (DME, 1 mL) was added dropwise to an ice-
cooled suspension of NaH (60% dispersion in mineral oil, 4.0 mg,
reduced pressure and the residue was co-evaporated with CH2Cl2
(3ꢃ5 mL) yielding infectopyrone (1) as a yellow solid (9.9 mg,
mol, 98%). IR (ATR): v 2921 cmꢂ1, 2852, 1679, 1622, 1600, 1552,
~
100
mmol) in anhydrous DME (2 mL) under Ar atmosphere and
37
m
stirred for 30 min. A soln of phomapyrone D (20.4 mg, 92
m
mol) in
1459, 1406, 1377, 1353, 1301, 1248, 1223, 1190, 1160, 1084, 1012, 913,
anhydrous DME (4 mL) was added dropwise to the ice-cooled re-
action mixture. The ice bath was removed after complete addition
and the mixture was stirred overnight at rt before quenching by
889, 865, 811, 747, 720, 702, 665, 582, 528, 510, 467, 434. 1H NMR
(400 MHz, DMSO-d6):
3H, CH3), 3.97 (s, 3H, OCH3), 5.78 (s, 1H, CH), 6.70 (s, 1H, CH), 6.85 (s,
1H, CH), 12.27 (br, 1H, COOH). 13C NMR (100 MHz, DMSO-d6):
d¼1.82 (s, 3H, CH3), 2.08 (s, 3H, CH3), 2.25 (s,
addition of satd aq NH4Cl soln (500
mL). After filtration over Na2SO4
d
¼8.6
and Celite, the solvent was removed and the residue purified by
column chromatography (silica gel, hexanes/EtOAc, 7:3) yielding
(CH3), 13.9 (CH3), 18.6 (CH3), 56.8 (OCH3), 95.3 (CH), 101.2 (C), 121.1
(CH), 129.5 (C), 133.0 (CH), 150.6 (C), 158.2 (C), 163.1 (C), 165.7 (C),
the pure (E,E)-isomer 33 (6.1 mg, 21
mmol, 23%) and a mixture of
167.0 (C). MS (EI): m/z (%)¼264 (69) [Mþ], 219 (100), 191 (19), 97
1H1616O5þꢁ, EI): calcd 264.0998 amu, found
12
isomers [(E,E)-33/(E,Z)-33¼6:4, 12.1 mg, 41
mmol, 45%] as yellow
(18). HRMS (½
C
14
oils. (E,E)-33: IR (KBr): v 3487 cmꢂ1, 3091, 2981, 2926, 2866, 2247,
1694, 1634, 1555, 1464, 1382, 1357, 1327, 1250, 1166, 1095, 1036,
1016, 910, 867, 804, 768, 752, 732, 646, 562, 521, 405. 1H NMR
264.1000 amu.5
~
6.7.4. (2Z,4E)-5-(4-Methoxy-3-methyl-2-oxo-2H-pyran-6-yl)-3-
(300 MHz, CDCl3):
2.07 (s, 3H, CH3), 2.30 (s, 3H, CH3), 3.93 (s, 3H, OCH3), 4.20 (q,
d
¼1.31 (t, J¼7.1 Hz, 3H, CH3), 1.96 (s, 3H, CH3),
methylhexa-2,4-dienoic acid [Z-1, (Z)-infectopyrone]. Infectopyrone
tert-butyl ester [(Z,E)-35, 3.4 mg, 10.6
mmol] was treated for 30 min
J¼7.1 Hz, 2H, CH2), 5.77 (s, 1H, CH), 6.25 (s, 1H, CH), 7.02 (s, 1H, CH).
with F3CCO2H (500 L) in CH2Cl2 (2 mL). The solvent was removed
under reduced pressure and the residue was co-evaporated with
m
13C NMR (100 MHz, CDCl3):
d
¼8.8 (CH3), 14.1 (CH3), 14.3 (CH3), 19.2
(CH3), 56.2 (CH3), 60.0 (CH2), 94.1 (CH), 103.6 (C), 120.4 (CH), 128.4
(C), 134.5 (CH), 152.0 (C), 159.0 (C), 164.5 (C), 165.4 (C), 166.3 (C). MS
CH2Cl2 (3ꢃ5 mL) yielding Z-infectopyrone (Z-1) as a yellow solid
~
(2.8 mg, 10.6
m
mol, quant.). IR (ATR): v 2922 cmꢂ1, 1681, 1624, 1602,
(EI): m/z (%)¼292 (61) [Mþ], 219 (85),195 (33),139 (48), 107 (43), 84
1551, 1440, 1406, 1379, 1353, 1301, 1248, 1224, 1190, 1162, 1084,
1009, 974, 913, 888, 858, 813, 746, 720, 684, 569, 528, 510, 468, 434.
12
(100) 77 (71). HRMS (½
C
1H2016O5þꢁ, EI): calcd 292.1311 amu,
16
found 292.1312 amu.
1H NMR (300 MHz, DMSO-d6):
d
¼1.82 (s, 3H, CH3), 1.91 (s, 3H, CH3),
2.03 (s, 3H, CH3), 3.96 (s, 3H, OCH3), 5.86 (s,1H, CH), 6.61 (s, 1H, CH),
6.7.2. (E,E)- and (E,Z)-tert-butyl 5-(4-methoxy-3-methyl-2-oxo-2H-
7.27 (s,1H, CH),12.18 (br,1H, COOH). 13C NMR (100 MHz, DMSO-d6):
pyran-6-yl)-3-methylhexa-2,4-dienoate [35, (E,E)- and (E,Z)-in-
d
¼8.6 (CH3),13.7 (CH3), 23.9 (CH3), 56.7 (OCH3), 94.3 (CH),100.8 (C),
fectopyrone tert-butyl ester]. nBuLi (95
m
L, 2.2 M in cyclohexane,
mol) was added under Ar atmosphere to an ice-cooled soln of
tert-butyl diethyl phosphonoacetate (34, 55.7 mg, 210 mol) in
anhydrous THF (2 mL) and stirred for 30 min. A soln of phoma-
pyrone D (12, 31.1 mg, 140 mol) in anhydrous THF (5 mL) was
120.7 (CH), 127.8 (C), 131.0 (CH), 150.3 (C), 158.3 (C), 163.2 (C), 165.8
210
m
(C), 166.2 (C). MS (EI): m/z (%)¼264 (71) [Mþ], 219 (100), 139 (26).
m
HRMS (½
C
14
1H1616O5þꢁ, EI): calcd 264.0998 amu, found 264.0995
12
amu.
m
added dropwise to the ice-cooled mixture. The ice bath was re-
moved after complete addition and the mixture was stirred over-
night at rt before quenching by addition of satd aq NH4Cl soln
Acknowledgements
(500
m
L), filtered (Na2SO4/Celite), and concentrated and the residue
We gratefully acknowledge Nils Jasinski for his help with the
laboratory work.
was purified by column chromatography (silica gel, hexanes/EtOAc,
7:3) yielding a mixture of isomers [(E,E)/(E,Z)¼2:1, 24.2 mg,
76 mmol, 54%] as a yellow oil. Separation of the isomers was ach-
~
ieved by MPLC (hexanes/EtOAc, 10:1). (E,E)-35: IR (KBr):
v
Supplementary data
2976 cmꢂ1, 2929, 1696, 1638, 1554, 1458, 1365, 1245, 1164, 1138,
1110, 1014, 897, 848, 769, 751, 598, 520, 409. 1H NMR (400 MHz,
Spectra for compounds 1, Z-1, 2e9, 12, 20, 21, 33, (E,E)-35, and
(E,Z)-35. Supplementary data related to this article can be found
CDCl3):
d
¼1.50 (s, 9H, C(CH3)3), 1.95 (s, 3H, CH3), 2.06 (d, J¼1.3 Hz,
3H, CH3), 2.25 (s, 3H, CH3), 3.92 (s, 3H, OCH3), 5.69 (q, J¼1.3 Hz, 1H,