Carboxylic analogs of tocopherols
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 2, February, 2006
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(1899). 1H NMR, δ: 1.30 (s, 3 H, C(2)Me); 1.70—2.15 (m, 4 H,
H(3), H(1´)); 2.18, 2.24, 2.30 (all s, 9 H, MeCarom); 2.50—2.78
(m, 4 H, H(4), H(2´)); 4.75 (s, 2 H, OCH2Ph); 7.35—7.70 (m,
5 H, HPh); 9.83 (t, 1 H, HCO, J = 1.0 Hz). 13C NMR, δ: 11.73,
11.84, 12.70 (MeCarom); 20.34 (C(4)); 23.34 (MeC(2)); 31.28,
31.74 (C(3), C(2´)); 38.38 (C(1´)); 73.51 (OCH2Ph); 74.52
(C(2)); 117.10, 122.75, 125.96, 127.98 (C(4а), C(5), C(7), C(8));
127.53, 127.63 (C(2)Ph—C(6)Ph); 137.71 (C(1)Ph); 147.16
(C(8a)); 148.26 (C(6)); 202.38 (CHO).
(OH). UV (MeOH), λmax/nm (ε): 242 (19048), 278 (2196), 295
(923), 328 (554). 1H NMR, δ: 1.32 (s, 3 H, MeC(2)); 1.82—2.05
(m, 4 H, H(3), H(1´)); 2.11 (s, 3 H, MeC(5)); 2.42 (s, 3 H,
MeCO2); 2.58—2.80 (m, 4 H, H(4), H(2´)); 7.40 (m, 2 H, H(8),
H(9)); 7.55, 8.15 (both d, 2 H, H(7), H(10), J = 7.7 Hz).
13C NMR (δ: 12.69 (MeC(5)); 20.55 (MeCO2); 21.51 (C(4));
23.81 (MeC(2)); 32.23 (C(3)); 33.04 (C(2´)); 37.01 (C(1´));
76.63 (C(2)); 115.74, 126.08, 127.17, 127.48 (C(4а), C(5), C(6а),
C(10а)); 121.44, 122.82, 125.64, 127.14 (C(7)—C(10)); 138.32
(C(10b); 147.59 (C(6)); 171.75 (MeCO); 179.80 (CO2H).
(2RS, 2´EZ )ꢀ6ꢀAcetoxyꢀ2ꢀ(3´ꢀacetoxypropꢀ2´ꢀenꢀ1´ꢀyl)ꢀ
2,5,7,8ꢀtetramethylchromane (18). A mixture of aldehyde 12
(2.6 g, 8.5 mmol), Ac2O (20 mL), and AcOK (0.13 g, 1.3 mmol)
was refluxed for 4 h and then concentrated in vacuo to ~2 mL,
and EtOAc (50 mL) was added. The solution was washed sucꢀ
cessively with NaHCO3 and H2O, dried with MgSO4, and conꢀ
centrated. The residue was chromatographed on SiO2 (30 g),
using a 5 : 1 nꢀhexane—EtOAc mixture as the eluent to give 1.9 g
(65%) of a mixture of enol acetates 18 (E/Z ≈ 2 : 1). Found (%):
C, 69.67; H, 7.74. C20H26O5. Calculated (%): C, 69.34; H, 7.56.
(2RS)ꢀ6ꢀAcetoxyꢀ2ꢀ(2ꢀcarboxyethyl)ꢀ2,5,7,8ꢀtetramethylꢀ
chromane (15). Jones reagent (1.2 mL, 3.36 mmol) (prepared
from 1.33 g of CrO3, 3.8 mL of H2O, and 1.2 mL of conc. H2SO4)
was added dropwise with vigorous stirring at 0 °C to a solution of
aldehyde 12 (0.86 g, 2.83 mmol) in acetone (20 mL), and the
mixture was stirred for 2 h at ~20 °C and extracted with EtOAc.
The extract was washed with brine, dried with MgSO4, and
concentrated. The residue was chromatographed on a column
with SiO2 (14 g) using methanol as the eluent to give 0.62 g
(68%) of acid 15, m.p. 149—150 °C (cf. Ref. 24). Found (%):
C, 67.71; H, 7.45. C18H24O5. Calculated (%): C, 67.48; H, 7.55.
IR, ν/cm–1: 1210, 1080 (C—O), 1740, 1700 (C=O), 3200—3500
(OH). UV (MeOH), λmax/nm (ε): 278 (1415); 284 (1489).
1H NMR, δ: 1.21 (s, 3 H, MeC(2)); 1.79—2.20 (m, 4 H, H(3),
H(1´)); 1.94, 1.97, 2.06 (all s, 9 H, MeCarom); 2.28 (s, 3 H,
MeCO2); 2.50—2.75 (m, 4 H, H(4), H(2´)). 13C NMR, δ: 12.02,
12.24, 13.11 (MeCarom); 20.46 (MeCO2); 21.38 (C(4)); 23.59
(MeC(2)); 29.51 (C(2´)); 32.26 (C(3)); 35.68 (C(1´)); 75.33
(C(2)); 118.63, 123.93, 126.30, 127.92 (C(4а), C(5), C(7), C(8));
142.21 (C(8а)); 150.11 (C(6)); 171.53 (MeCO2); 177.57 (CO2H).
(2RS)ꢀ6ꢀBenzyloxyꢀ2ꢀ(2ꢀcarboxyethyl)ꢀ2,5,7,8ꢀtetramethylꢀ
chromane (16). A solution of AgNO3 (0.32 g, 1.9 mmol) in water
(3.8 mL) was added to a solution of aldehyde 13 (0.55 g,
1.6 mmol) in EtOH (25 mL). The mixture was stirred for 5 min
at ~20 °C, and a solution of NaOH (0.31 g, 7.8 mmol) in H2O
(8.9 mL) was added dropwise. The mixture was stirred for 2 h at
~20 °C and filtered, and the filtrate was concentrated in vacuo to
~5 mL. The residue was dissolved in H2O (20 mL) and washed
with EtOAc. The aqueous solution was acidified with 1 M HCl
and extracted with EtOAc, and the extract was washed with
brine, dried with MgSO4, and concentrated to give 0.43 g (73%)
of acid 16, m.p. 76—78 °C. Found (%): C, 74.63; H, 7.39.
C23H28O4. Calculated (%): C, 74.97; H, 7.66. IR, ν/cm–1: 1700
(C=O), 3300—3600 (OH). UV (EtOH), λmax/nm (ε): 203
(62191); 287 (1974). 1H NMR, δ: 1.33 (s, 3 H, MeC(2));
1.81—2.15 (m, 4 H, H(3), H(1´)); 2.14, 2.23, 2.28 (all s, 9 H,
MeCarom); 2.50—2.80 (m, 4 H, H(4), H(2´)); 4.76 (s, 2 H,
OCH2Ph); 7.37—7.57 (m, 5 H, HPh). 13C NMR, δ: 11.73, 11.92,
12.78 (MeCarom); 20.42 (C(4)); 23.31 (MeC(2)); 28.54 (C(2´));
31.37 (C(3)); 34.31 (C(1´)); 73.53 (OCH2Ph); 74.67 (C(2));
117.20, 122.83, 126.01, 127.95, (C(4а), (C(5), C(7) C(8));
127.66, 128.38 (C(2)Ph—C(6)Ph); 137.87 (C(1)Ph); 147.34
(C(8a)); 148.36 (C(6)); 180.12 (CO2H).
IR, ν/cm–1: 1760, 1740 (OC=O), 1650 (C=C). UV (CHCl3),
1
λ
max/nm (ε): 263 (1951), 286 (2123). H NMR, δ: 1.30 (s, 3 H,
MeC(2)); 1.72—1.90 (m, 2 H, H(3)); 2.00, 2.05, 2.13 (all s,
12 H, MeCarom, MeCO2C(3´)); 2.20—2.47 (m, 2 H, H(1´));
2.31 (s, 3 H, MeCO2Ar); 2.50—2.72 (m, 2 H, H(4)); 5.05 (dt,
~0.3 H, H(2´) in the Zꢀisomer, J = 7.2, 6.5 Hz); 5.52 (dt, ~0.7 H,
H(2´) in the Eꢀisomer, J = 12.5, 8.0 Hz); 7.16 (m, 1 H, (H(3´)).
13C NMR, δ: 11.58, 11.81, 12.67 (MeCarom); 13.88 (MeC(2));
20.22, 20.28, 20.33 (MeCO2C(3´), MeCO2Ar); 22.41 (C(4));
27.24 (C(1´) in the Zꢀisomer); 30.46 (C(1´) in the Eꢀisomer);
31.36 (C(3)); 74.34, 74.52 (C(2)); 108.47 (C(2´) in the Zꢀisoꢀ
mer); 109.52 (C(2´) in the Eꢀisomer); 116.86, 116.92, 122.78,
122.69, 124.77, 126.57, 126.62 (C(4a), C(5), C(7), C(8)); 135.64
(C(3´) in the Zꢀisomer); 137.11 (C(3´) in the Eꢀisomer); 140.46,
140.58 (C(8a)); 148.78 and 148.72 (C(6)); 167.67 (MeCO2(3´)
in the Eꢀisomer); 168.67 (MeCO2(3´) in the Zꢀisomer); 169.31
(MeCO2Ar).
(2RS, 2´EZ )ꢀ2ꢀ(3´ꢀAcetoxypropꢀ2´ꢀenꢀ1´ꢀyl)ꢀ6ꢀbenzyloxyꢀ
2,5,7,8ꢀtetramethylchromanes (19). A mixture of aldehyde 13
(0.91 g, 2.6 mmol), Ac2O (5 mL), and AcOK (0.04 g, 0.41 mmol)
was refluxed for 4 h and concentrated in vacuo to 1 mL, and
EtOAc (20 mL) was added. The solution was washed succesꢀ
sively with NaHCO3 and H2O, dried with MgSO4, and concenꢀ
trated. The residue was chromatographed on SiO2 (20 g) using a
5 : 1 nꢀhexane—EtOAc mixture as the eluent to give 0.76 g
(74%) of enol acetates 19 (E/Z ≈ 2 : 1). Found (%): C, 75.82;
H, 7.81. C25H30O4. Calculated (%): C, 76.11; H, 7.66. IR,
ν/cm–1: 1760 (C=O), 1680 (C=C). UV (EtOH), λmax/nm (ε):
287 (3120). 1H NMR, δ: 1.30, 1.34 (both s, 3 H, MeC(2));
1.75—2.00 (m, 2 H, H(3)); 2.11, 2.19, 2.24 (all s, 9 H, MeCarom);
2.29 (s, 3 H, MeCO2); 2.40—2.60 (m, 2 H, H(1´)); 2.60—2.95
(m, 2 H, H(4)); 4.75 (s, 2 H, OCH2Ph); 5.14 (dt, ~0.3 H, H(2´)
in the Zꢀisomer, J = 7.0, 6.5 Hz); 5.60 (dt, ~0.7 H, H(2´) in the
Eꢀisomer, J = 12, 8.0 Hz); 7.20 (m, 1 H, H(3´)); 7.25—7.60 (m,
5 H, HPh). 13C NMR, δ: 11.50, 11.62, 12.50 (MeCarom); 20.10;
20.49 (MeCO2); 20.26 (C(4)); 23.54, 23.75 (MeC(2)); 30.63,
30.79 (C(3)); 34.02 (C(1´) in the Zꢀisomer); 37.22 (C(1´) in the
Eꢀisomer); 73.97, 74.17, 74.31 (C(2), OCH2Ph); 108.47 (C(2´)
in the Zꢀisomer)); 109.48 (C(2´) in the Eꢀisomer); 116.97,
117.03, 122.58, 125.62, 127.85 (C(4а), C(5), C(7), C(8)); 127.32,
127.39, 128.08, 128.15 (C(2)PhꢀC(6)Ph); 135.68, 136.97
(2RS)ꢀ6ꢀAcetoxyꢀ2ꢀ(2ꢀcarboxyethyl)ꢀ2,5ꢀdimethylꢀ3,4ꢀdiꢀ
hydroꢀ2Hꢀnaphtho[1,2ꢀb]pyran (17). Jones reagent (1.0 mL,
2.8 mmol) was added at 0 °C with vigorous stirring to a solution
of aldehyde 14 (0.66 g, 2.0 mmol, prepared as described previꢀ
ously22) in acetone (10 mL). The mixture was stirred for 2 h at
~20 °C and then workedꢀup as described above (see the preparaꢀ
tion of acid 15) to give 0.44 g (64%) of acid 17, m.p. 150—152 °C.
Found (%): C, 69.85; H, 6.63. C20H22O5. Calculated (%):
C, 70.16; H, 6.48. IR, ν/cm–1: 1760, 1710 (C=O), 2800—3600