P. S. Vraka et al. / Bioorg. Med. Chem. 14 (2006) 2684–2696
2693
00
00
(s, 3H, H3CO(O)C4 –), 3.04 (dd, 1H, C3 HAHB), 2.81 (dd,
1.90 (s, 3H, C13H3), 1.86 (s, 3H, C14H3), 1.70 (m, 2H,
00
1H, C3 HAHB). 13C{1H} NMR d (CDCl3) (ppm): 178.40
C H2), 1.38 (m, 3H, C H, C H, C 0H), 1.16 (s, 3H,
C11H3), 1.35–0.9 (m, 18H, –C0H2-phytyl), 0.78(m,
12H, H3C-phytyl). 13C{1H} NMR d (CDCl3) (ppm):
3
4
8
12
0
0
00
00
00
00
100
800
(C ), 171.50 (C4 ), 136.62 (C6 , C10 ), 1020 9.69 (C7 , C ,
00
00
00
C9 ), 126.79 (C5 ), 52.54 (H3CO(O)C4 ), 37.21 (C2 ),
00
00
100
36.95 (C3 ). 77Se NMR d (CDCl3) (ppm): 646.95 (d).
The numbering is according to Scheme 4.
(7b) 177.93 (C ), 170.16 (C4 ), 149.93 (C9), 140.75
00 00 00 00
900
(C6), 136.66 (C6 ,C10 ), 129.78 (C7 , C ), 129.40 (C8 ),
00
127.65 (C7), 127.03 (C5), 125.33 (C5 ), 123.50 (C10),
117.87 (C8), 75.48 (C2), (39.81, 37.81, 37.72, 33.19,
4.1.3. Synthesis of phenylselenyl succinic acid (5). HCl
12 N (10 mL) was added to 4 (0.70 g, 2.40 mmol) and
the mixture was refluxed overnight at 75 ꢁC. The solution
was cooled at room temperature and a white solid was
precipitated. The solid was filtered, washed with CH2Cl2
(2· 3 mL), and dried under vacuum. The yield was
0.55 g (82%). Found: C, 43.23; H, 3.92. C10H10O4Se
0.25H2O requires: C, 43.26; H 3.81. 1H NMR d (CD3CN)
300
33.11, 25.22, 21.45) (C0H2-phytyl), 36.89 (C ), 37.12
00
0
0
0
(C2 ), 31.46 (C3), 28.39 (C4 , C8 , C12 ), 24.86 (C11),
0
0
(23.14, 23.05) (H3CC4 , H3CC8 ), 20.98 (C4), (20.10)
0
((H3C)2C12 ), 13.37 (H3CC14), 12.53 (H3CC13), 12.22
00
00
(H3CC12); (7a) 176.93 (C400 ), 171.53 (C1 ), 149.93 (C900),
00
00
140.67 (C600), 135.98 (C6 , C10 ), 129.70 (C7 , C9 ),
00
129.40 (C8 ), 127.38 (C7), 126.86 (C5), 125.93 (C5 ),
123.50 (C10), 117.87 (C8), 75.48 (C2), (39.81, 37.81,
37.72, 33.19, 33.11, 25.12, 21.45) (C0H2-p0hytyl), 37.52
00
00
00
(ppm): 7.63 (d, 2H, C6 H, C10 H), 7.40 (m, 3H, C7 H,
00
00
00
C8 H, C9 H), 3.87 (dd, 1H, C2 HX), 2.77 (m, 2H,
00
00
00
0
0
C3 H2). 13C{1H} NMR d (CD3CN) (ppm): 173.20
(C3 ), 36.27 (C2 ), 31.46 (C3), 28.39 (C4 , C80 , C12 ),
00
00
00
00
00
0
700
(C1 ), 172.20 (C4 ), 136.20 (C6 , C10 ), 130.00 (C , C9 ),
24.86 (C11), (23.14, 23.05) (H3CC4 , H3CC8 ), 20.98
00
00
00
00
0
129.40 (C8 ), 127.2 (C5 ), 37.00 (C2 ), 36.60 (C3 ). 77Se
NMR d (CD3CN) (ppm): 634.80 (d). The numbering is
according to Scheme 4.
(C4), (20.10) ((H3C)2C12 ), 13.37 (H3CC14), 12.53
(H3CC13), 12.22 (H3CC12). 77Se NMR d (CDCl3)
(ppm): (7b) 652.10 (d), (7a) 635.70 (d). The numbering
is according to Scheme 4.
4.1.4. Synthesis of phenylselenyl succinic anhydrite (6).
Compound 5 (0.55 g, 2.00 mmol) and excess acetic
anhydrite (10 mL) were stirred at 30 ꢁC for 2 h. Acetic
anhydrite was evaporated under vacuum resulting in
4.1.6. Synthesis of c-tocopheryl-2-phenylselenyl Succinate
(8). Compounds 1c and 6 were used in the same mole ratio
like in the synthesis of 7, and similar preparation and puri-
fication procedures were followed. The yield was 50% in
the brownish oil containing 8a and b whose ratio varied
from 40% to 60% in each component. TLC (hexane–
CHCl3, 1:5) R1c = 0.59, R8 = 0.31. Found: C, 67.79; H,
1
0.51 g (100%) of a brown solid. H NMR d (CD3CN)
00
00
00
00
00
(ppm): 7.68 (C6 H, C10 H), 7.42 (C7 H, C8 H, C9 H),
00
00
4.39 (dd, 1H, HXC2 ), 3.53 (dd, 1H, C3 HAHB), 2.94
00
(dd, 1H, C3 HAHB). 13C NMR d (CD3CN) (ppm):
00
00
00
00
173.70 (C1 ), 172.73 (C4 ), 137.0300 (C6 , C10 ), 130.56
8.25. C38H56O5Se requires: C, 67.94; H, 8.40.00 H NMR
1
00
00
00
00
(C7 , C9 ), 129.95 (C8 ), 127.65 (C5 ) 37.41 (C2 ), 36.26
d (CDCl3) (ppm): (8b) 9.70 (br, 1H, HO(O)C1 ), 7.70 (d,
00
00
00
00
00
00
(C3 ). 77Se NMR d (CD3CN) (ppm): 668.52 (d). The
numbering is according to Scheme 4.
2H, C6 H, C10 H), 7.33 (m, 3H, C7 H, C8 H, C9 H), 6.51
00
00
(s, 1H, C5H), 4.09 (dd, 1H, C2 HX), 3.12 (dd, 1H, C3
00
(HA)(HB)), 2.96 (dd, 1H, C3 (HA)(HB)), 2.69 (m, 2H,
4.1.5. Synthesis of a-tocopheryl-2-phenylselenyl succinate
(7). Compound 6 (0.58 g, 2.3 mmol) and ZnCl2 powder
(0.17 g, 1.3 mmol) were added to a dry toluene solution
(20 mL) of 1a (0.30 g, 0.70 mmol). The whole mixture
was stirred and refluxed under N2 for one day. Next
the mixture was filtered and the solvent was removed
under vacuum. The oily residue was dissolved in 1–
2 mL CHCl3 and was passed through a well-packed
chromatography column using as eluents first n-hexane,
then a mixture of chloroform–n-hexane (5:1) and finally
chloroform. The solvent was evaporated yielding 0.27 g
(55%) of brownish oil containing 7a and b, whose ratio
varied from 40% to 60% in each component. TLC (hex-
ane–CHCl3, 1:5) R1a = 0.69, R7 = 0.11. Found: C, 68.91;
H, 8.84. C39H58O5SeÆ0.3n-hexane requires: C, 68.86; H,
C4H2), 2.17 (s, 3H, C13H3), 2.11 (s, 3H C14H3), 1.73 (m,
3
4
8
12
2H, C H2), 1.51 (m, 3H, C H, C H, C 0H), 1.29 (s,
0
0
3H, C11H3), 1.45–1.00 (m, 18H, C0H2-phytyl), 0.86 (m,
00
12H, H3C-phytyl); (8a) 9.70 (br, 1H, 00HO(O0)0 C4 ), 7.70
00
00
00
(d, 2H, C6 H, C10 H), 7.33 (m, 3H, C7 H, C8 H, C9 H),
00
6.55 (s, 1H, C5H), 4.16 (dd, 1H, C2 HX), 3.09 (dd, 1H,
00
00
C3 (HA)(HB)), 2.94 (dd, 1H, C3 (HA)(HB)), 2.69 (m, 2H,
C4H2), 2.17 (s, 3H, C13H3), 2.11 (s, 3H, C14H3), 1.73 (m,
0
0
0
2H, C3H2), 1.51 (m, 3H, C4 H, C8 H, C12 H), 1.29 (s,
3H, C11H3), 1.45–1.00 (m, 18H, C0H2-phytyl), 0.86 (m,
12H, H3C-phytyl). 13C{1H} NMR d (CDCl3) (ppm):
00
00
(8b) 178.74 (C1 ), 170.49 (C4 ), 150.12 (C9), 141.82 (C6),
00
00
00
00
700
136.80 (C6 , C10 ), 129.79 (C , C9 ), 127.86 (C8 ), 127.41
00
(C7), 119.13 (C5), 126.35 (C5 ), 118.90 (C10), 118.84 (C8),
76.46 (C2), (40.69, 39.82, 37.89, 37.73, 29.83, 28.43,
1
300
8.81. H NMR d (CDCl3) (ppm): (7b) 11.10 (br, 1H,
25.64, 24.66, 22.68) (C0H2-phytyl), 37.09 (C ), 37.25
00
00
00
00
0
0
0
HO(O)C1 ), 7.71 (d, 2H, C6 H, C10 H), 7.36 (m, 3H,
(C2 ), 31.44 (C3), 33.18 (C4 , C80 , C12 ), 24.66 (C11),
00
00
00
00
0
C7 H, C8 H, C9 H), 4.02 (dd, 1H, C2 HX), 3.12 (dd,
(23.20, 22.86) (H3CC4 , H3CC8 ), 21.45 (C4), 20.17
00
00
0
1H, C3 (HA)(HB)), 3.02 (dd, 1H, C3 (HA)(HB)), 2.47
(m, 2H, C4H2), 1.99 (s, 3H, C12H3), 1.90 (s, 3H,
C13H3), 1.86 (s, 3H C14H3), 1.70 (m, 2H, C3H2), 1.38
((H3C)2C12 ), 13.06 (H3C14), 12.39 (H3C13); (8a) 177.73
00
00
00
(C4 ), 171.80 (C1 ), 150.12 (C9), 141.73 (C6), 136.47 (C6 ,
00
00
00
700
C10 ), 129.57 (C , C9 ), 127.86 (C8 ), 127.05 (C7), 118.93
0
0
0
00
(m, 3H, C4 H, C8 H, C12 H), 1.16 (s, 3H, C11H3), 1.35–
(C5), 126.71 (C5 ), 118.90 (C10), 118.84 (C8), 76.46 (C2),
(40.69, 39.82, 37.89, 37.73, 29.83, 28.43, 25.64, 24.66,
0.9 (m, 18H, C0H2-phytyl), 0.78 (m, 12H, H3C-phyt0y0 l);
00
300
200
(7a) 11.1 (br, 1H, HO(O)C4 ), 7.71 (d, 2H, C6 H,
22.68) (C0H2-phytyl), 37.37 (C ), 36.63 (C ), 31.44
0 0 0
00
00
00
00
C10 H), 7.36 (m, 3H, C7 H, C8 H, C9 H), 4.15 (dd, 1H0,0
(C3), 33.18 (C4 ,0 C8 , C12 ), 24.66 (C11), (23.200, 22.86)
00
00
0
C2 HX), 3.05 (dd, 1H, C3 (HA)(HB)), 2.85 (dd, 1H, C3
(HA)(HB)), 2.47 (m, 2H, C4H2), 2.01 (s, 3H, C12H3),
(H3CC4 , H3CC8 ), 21.45 (C4), 20.17 ((H3C)2C12 ), 13.06
(H3C14), 12.39 (H3C13). 77Se NMR d (CDCl3) (ppm):