delineate the role of structural requirements and their corre-
lation with the HO competition.
(t, 3H, J = 7.6), 1.97 (s, 3H), 2.39 (s, 3H), 4.28 (q, 2H, J = 7.6),
6.15 (s, 1H), 6.83 (d, 1H, J = 8.3), 7.15 (d, 1H, J = 8.3); δC 13.9,
19.1, 21.9, 62.7, 78.4, 105.1, 112.7, 113.1, 118.6, 134.9, 150.6,
152.6, 154.2, 160.3, 178.5; ESIMS: m/z 291 (M ϩ H)ϩ, 313 (M
ϩ Na)ϩ. From the next band compound 8 (16 mg, 8%) was
isolated, mp 236–238 ЊC (from ethanol) (lit.17 mp 236–238 ЊC).
ؒ
We also determined the inhibition of Fe2ϩ–stimulated oxid-
ation of linoleic acid by compounds 4b, 12a–c and 18 in order
to find out if the tested compounds act as antioxidants in a
nonbiological system. All compounds (except 4b) inhibited this
type of lipid peroxidation (22–50.7%). Compound 12a showed
the highest inhibition. No attempt was made to find the concen-
tration of compound which produces maximal inhibition.
Our attempt to correlate our biological results with some
physicochemical parameters was unsuccessful. However our
preliminary results seem to correlate with the literature values
for potency of the 7,8 disubstituted coumarinic derivatives.
Certain similarities in the biological screening exist between the
ayapin structure and 4b. It could be possible that no specificity
exists in the presence of a 6–7 or a 7–8 fused ring. Furthermore
lipophilicity in our case does not seem to affect predominantly
the biological activity. On the contrary sterimol parameters
(expressing steric requirements) are more important.
Reactions of quinone 1 with ylide 2b. Synthesis of ethyl
2-ethyl-6-methyl-8-oxo-8H-[1,3]dioxolo[4,5-h]chromene-2-carb-
oxylate 4b and ethyl 2-(7-hydroxy-4-methyl-2-oxo-2H-chromen-
8-yloxy)butanoate 9. A. A mixture of quinone 1 (0.38 g, 2
mmol) and ylide 2b (0.752 g, 2 mmol) in DCM (10 cm3) was
stirred at room temperature for 30 min (consumption of quin-
one) and the mixture was then concentrated. Column chrom-
atography [hexane–ethyl acetate (4 : 1 to 1 : 1)] gave after the
elution of triphenylphosphine (52 mg, 10%) compound 4b
(71 mg, 12%), mp 60–61 ЊC (hexane–ether) (Found: C, 63.3; H,
5.4. C16H16O6 requires C, 63.15; H, 5.3%); νmax/cmϪ1 3050, 1740,
1715, 1630; δH 1.08 (t, 3H, J = 7.4), 1.31 (t, 3H, J = 7.1), 2.30 (q,
2H, J = 7.4), 2.39 (s, 3H), 4.28 (q, 2H, J = 7.1), 6.15 (s, 1H), 6.84
(d, 1H, J = 8.4), 7.14 (d, 1H, J = 8.4); δC 6.2, 14.0, 19.1, 28.3,
62.6, 77.9, 105.0, 112.6, 112.8, 118.7, 133.9, 146.4, 152.8, 156.6,
162.0, 177.2; EIMS: m/z 304 (48%, Mϩ), 258 (19), 231 (94), 230
(58), 203 (93), 201 (46), 91 (98), 57 (100). Coumarin 817 (39 mg,
10%) was eluted next.
B. A mixture of quinone 1 (95 mg, 0.5 mmol) and ylide 2b
(0.188 g, 0.5 mmol) in DCM (4 cm3) was stirred at Ϫ10 ЊC for 4
h. After evaporation of the solvent the residue was separated by
column chromatography [hexane–ethyl acetate (6 : 1)] to give
after the elution of triphenylphosphine (16 mg, 12%) com-
pound 9 (25 mg, 16%), mp 102–104 ЊC (DCM–hexane) (Found:
C, 63.0; H, 6.1. C16H18O6 requires C, 62.75; H, 5.9%); νmax/cmϪ1
3230, 3050, 1710, 1690, 1590; δH 1.24 (t, 3H, J = 7.2), 1.28 (t,
3H, J = 7.1), 2.05–2.2 (m, 1H), 2.3–2.5 (m, 1H), 2.38 (s, 3H),
4.19 (dq, 1H, J1 = 7.1, J2 = 10.7), 4.29 (dq, 1H, J1 = 7.1, J2 =
10.7), 4.76 (dd, 1H, J1 = 4.4, J2 = 6.3), 6.11 (s, 1H), 6.92 (d, 1H,
J = 8.8), 7.27 (d, 1H, J = 8.8), 8.75 (s, 1H); δC 9.1, 14.0, 18.9,
26.7, 62.3, 82.3, 111.4, 113.2, 113.8, 120.8, 132.8, 147.5, 153.1,
153.3, 160.2, 175.2; ESIMS: m/z 307 (M ϩ H)ϩ, 329 (M ϩ
Na)ϩ. Compound 4b (19 mg, 12.5%) was eluted next.
Experimental
Mps were measured on a Kofler hot-stage apparatus and are
uncorrected. IR spectra were obtained using a Perkin-Elmer
1310 spectrophotometer as Nujol mulls except otherwise stated.
NMR spectra were recorded on a Bruker AM 300 (300 MHz
and 75 MHz for 1H and 13C respectively) or on a Bruker
AMX-400 (162 MHz for 31P NMR) spectrometers using CDCl3
as solvent and TMS as an internal standard. J values are
reported in Hz. Mass spectra were determined on a VG-250
spectrometer at 70 eV under Electron Impact (EI) conditions,
or on a Perkin-Elmer API 100 Sciex Single quadrupole under
Electronspray (ESI) conditions. High resolution mass spectra
(HRMS) were recorded on an Ionspec mass spectrometer under
matrix-assisted laser desorption/ionization Fourier transform
mass spectrometry (MALDI-FTMS) conditions with 2,5-
dihydroxybenzoic acid (DHB) as the matrix. Microanalyses
were performed on a Perkin-Elmer 2400-II Element analyzer.
THF was refluxed over sodium and benzophenone and distilled
when the mixture turned blue. Silica gel N0 60, Merck A. G. has
been used for column chromatographies. o-Quinones 134 and
1335 were prepared according to the literature method.
Reactions of quinone 1 with ylide 2c. Synthesis of ethyl 2-
benzyl-6-methyl-8-oxo-8H-[1,3]dioxolo[4,5-h]chromene-2-carb-
oxylate 4c. A. A mixture of quinone 1 (0.19 g, 1 mmol) and
ylide 2c (0.424 g, 1 mmol) in DCM (10 cm3) was stirred at room
temperature for 24 h. The reaction mixture was concentrated
and the residue was separated by column chromatography
[hexane–ethyl acetate (75 : 25 to 0 : 100)] to give compound 4c
(17 mg, 5%), mp 150–151 ЊC (DCM–hexane); νmax/cmϪ1 (KBr)
3060, 2923, 2850, 1732, 1715, 1640; δH 0.86 (t, 3H, J = 7.6), 2.34
(s, 3H), 3.55 (s, 2H), 4.24 (q, 2H, J = 7.6), 6.12 (s, 1H), 6.76 (d,
1H, J = 8.9), 7.06 (d, 1H, J = 8.9), 7.15–7.4 (m, 5H); δC 14.0,
19.0, 29.7, 62.8, 81.4, 105.0, 111.5, 112.8, 118.6, 121.0, 128.5,
130.0, 130.8, 130.9, 143.7, 150.4, 156.8, 166.0, 177.4; EIMS: m/z
366 (24%, Mϩ), 365 (22), 293 (100), 275 (32), 231 (10), 203 (36),
91 (98). MALDIHRMS (DHB): m/z 367.1190 [M ϩ H]ϩ.
C21H19O6 requires m/z 367.1176. Coumarin 817 (30 mg, 16%)
was then eluted.
B. Quinone 1 (0.19 g, 1 mmol) was added at once to a solu-
tion of ylide 2c (0.424 g, 1 mmol) in dry DCM (10 cm3) at Ϫ10
ЊC and the reaction mixture was stirred at this temperature for 6
h (consumption of quinone). The solvent was then evaporated
and the residue was separated by column chromatography
[hexane–ethyl acetate (80 : 20 to 0 : 100)] to give triphenylphos-
phine (16 mg, 6%), compound 4c (8 mg, 2%) and coumarin 817
(80 mg, 42%).
Synthesis
Reaction of quinone 1 with ylide 2a. Synthesis of ethyl 2,6-
dimethyl-8-oxo-8H-[1,3]dioxolo[4,5-h]chromene-2-carboxylate
4a and 8-[1-carboxy-1-(triphenylphosphonio)ethoxy]-4-methyl-
2-oxo-2H-chromen-7-olate 6. A mixture of quinone 1 (0.19 g, 1
mmol) and ylide 2a (0.362 g, 1 mmol) in DCM (10 cm3) was
stirred at Ϫ10 ЊC for 4 h. After the consumption of quinone the
mixture was concentrated and treated with DCM–hexane to
give pure 6 as white crystals (0.147 g, 28%), mp 126–128 ЊC
(methanol–ethyl acetate) (Found: C, 70.9; H, 4.8. C31H25O6P
requires C, 71.0; H 4.8%); νmax/cmϪ1 3040, 2710, 2660, 2590,
1710, 1690, 1630, 1580; νmax/cmϪ1 (KBr) 3056, 2988, 2920, 2850,
2750, 2670, 2560, 1724, 1710, 1642, 1618, 1590; δH 2.32 (d, 3H,
J = 19.1), 2.35 (s, 3H), 5.99 (s, 1H), 6.94 (d, 1H, J = 8.9), 7.27 (d,
1H, J = 8.9), 7.57–7.68 (m, 6H), 7.70–7.76 (m, 3H), 8.01–8.09
(m, 6H), 14.68 (br s, 1H); δC 19.0, 21.3 (d, J = 2.4), 91.9 (d, J =
47.2), 110.0, 112.4, 116.3, 118.9 (d, J = 83.1), 122.1, 129.5 (d, J =
12.8), 130.4 (d, J = 4.9), 134.3 (d, J = 2.9), 135.6 (d, J = 9.4),
149.3, 153.7, 158.4 (d, J = 2.4), 160.5, 170.9 (d, J = 7.3); δP 36.8;
ESIMS: m/z 525 (M ϩ H)ϩ, 547 (M ϩ Na)ϩ; MALDIHRMS
(DHB): m/z 507.1355 [MHϩ Ϫ H2O]ϩ. C31H24O5P requires m/z
507.1356.
The filtrate was separated by column chromatography
[hexane–ethyl acetate (5 : 2)] to give after elution of triphenyl-
phosphine (8 mg, 3%) compound 4a (20 mg, 7%) mp 117–119
ЊC (DCM–hexane) (Found: C, 62.0; H, 5.1. C15H14O6 requires
C, 62.05; H 4.85%); νmax/cmϪ1 3050, 1740, 1720, 1635; δH 1.30
Reaction of quinone 1 with ylide 11a. Synthesis of 2,6-
dimethyl-2-phenyl-8H-[1,3]dioxolo[4,5-h]chromene-8-one 12a. A
1.6 M solution of BuLi in hexane (0.204 g, 3.2 mmol, 2 cm3)
3076
J. Chem. Soc., Perkin Trans. 1, 2001, 3073–3079