OH), 3.79 (m, 1H), 3.63 (m, 1H), 3.58 (s, 3H, COOMe), 2.58
(t, 2H, J 6.5), 2.29 (t, 2H, J 7), 1.58 (m), 1.29 (m, 10H); δC (75
MHz, CDCl3) 188.6, 174.3, 156.7, 142.1, 139.3, 137.3, 129.9,
128.2, 125.6, 80.4, 75.3, 74.8, 69.8, 51.5, 35.7, 33.3, 31.4, 31.0,
29.5, 25.9, 21.0; m/z (Cl/NH3) 530 and 528 [M ϩ NH4]ϩ.
COOMe), 2.56 (t, 2H, J 7.3), 1.65 (s, 3H, isopr.), 1.55–1.44
(m, 6H), 1.53 (s, 3H, isopr.); δC (62.5 MHz, CDCl3) 185.4,
166.2, 153.9, 141.8, 137.9, 137.0, 134.3, 131.4, 131.3,
130.7,129.0, 128.0, 128.0, 125.4, 109.2, 86.5, 81.2, 51.9, 35.4,
30.8, 30, 26.1, 26.8, 25.1; m/z (Cl/NH3) 544 and 542 [M ϩ
NH4]ϩ, 527 and 525 [M ϩ H]ϩ.
20
Compound 34. [α]D Ϫ42 (c 1, CHCl3), Ϫ54 (c 1, MeOH);
νmax (cmϪ1, CDCl ) 3398 (OH), 1712 (C᎐O); δ (250 MHz,
(Z ) and (E )-[4-Bromo-2(S )-hydroxy-2-(1(R)-hydroxy-5-phenyl-
pentyl)-5-oxo-cyclopent-3-enylidenemethyl]-benzoic acid methyl
ester (39) and (40)
᎐
3
H
CDCl3) 7.40 (s, 1H), 7.29–7.13 (m, 5H, arom-H), 6.42 (d, 1H,
J 7.8), 5.36 (dd, 1H, J 7.8 and 3.6), 4.65 (br s, 2H, OH), 4.48
(m 1H), 3.80 (dd, 1H, J 2 and 10), 3.22 (br s, 1H, OH), 2.58 (t,
2H, J 6.5), 2.41 (m, 2H), 1.96–1.48 (m, 10H); δC (62,5 MHz,
CDCl3) 188.6, 172.2, 156.9, 142.0, 138.1, 137.3, 129.6, 128.1,
128.0, 125.4, 82.7, 80.2, 75.0, 68.0, 35.5, 33.4, 31.4, 30.9, 29.4,
25.6, 22.8, 17.7; m/z (Cl/NH3) 498 and 496 [M ϩ NH4]ϩ.
Treatment of a mixture of compounds 37 ϩ 38 (70 mg, 0.16
mmol) following the same procedure as for compounds 30 ϩ 31
furnished the major compound (Z) 39 (18 mg, 23%) and
compound (E) 40 (46 mg, 60%).
Major compound (Z ) 39. [α]D20 Ϫ28 (c 0.5, CHCl3); Found C,
62.03; H, 5.43. Calc. for C25H25BrO5 (484.09) C, 61.86; H,
5.19%; νmax (cmϪ1, CDCl ) 3589 (OH), 1718 (C᎐O), 1627 (C᎐O
ester); δH (250 MHz, CDCl3) 8.06 (br d, 2H, J 3), 8.00 (br d, 2H,
J 3), 7.41 (s, 1H), 7.34–7.14 (m, 6H, arom-H), 3.93 (s, 3H,
COOMe), 3.91 (m, 1H), 2.79 (s, 1H, OH), 2.62 (t, 2H, J 6.5),
2.30 (d, 1H, J 4.4, OH), 1.61–1.25 (m, 6H); δC (62.5 MHz,
CDCl3) 186.0, 166.4, 154.3, 142.1, 137.5, 137.2, 136.4, 132,1,
131.0, 129.2, 128.2, 125.6, 81.1, 75.9, 52.2, 35.7, 31.3, 31.0, 25.8;
m/z (Cl/NH3) 504 and 502 [M ϩ NH4]ϩ, 487 and 485 [M ϩ H]ϩ.
6(E )-[4-Bromo-2(S )-hydroxy-2-(1(R)-hydroxy-5(S )-phenyl-
pentyl)-5-oxo-cyclopent-3-enylidene]-(5R),(6R)-dihydroxy-hep-
tanoic acid methyl ester (33) and 6(S )-{2(Z )-[4-bromo-2(S )-
hydroxy-2-(1(R)-hydroxy-5-phenyl-pentyl)-5-oxo-cyclopent-3-
enylidene]-1(R)-hydroxy-ethyl}-tetrahydro-pyran-2-one) (35)
᎐
᎐
3
Treatment of compound 31 (130 mg, 0.22 mmol) following the
same protocol as for compound 30, furnished compound
33 (21 mg, 19%) and lactone 35 (561 mg, 58%). Similarly,
treatment of lactone (E) 35 (31 mg, 0.06 mmol) in the same
conditions as for lactone 34 afforded compound 33 (33 mg,
100%).
20
Minor compound (E ) 40. [α]D ϩ32 (c 0.23, CHCl3); Found
C, 61.98; H, 5.37. Calc. for C25H25BrO5 (484.09) C, 61.86; H,
20
5.19%; νmax (cmϪ1, CDCl ) 3582 (OH), 1718 (C᎐O), 1635 (C᎐O
Compound 33. [α]D Ϫ43 (c 1, MeOH); Found C, 56.13; H,
᎐
᎐
3
5.97. Calc. for C24H31O7Br (511.41) C, 56.37; H, 6.11%; νmax
ester); δH (300 MHz, CDCl3) 8.07 (br d, 2H, J 8.3), 8.00 (br d,
2H), 7.61 (s, 1H), 7.59 (s, 1H), 7.29–7.12 (m, 5H, arom-H), 4.08
(m, 1H), 3.94 (s, 3H, COOMe), 2.68 (s, 1H, OH), 2.59 (t, 2H,
J 7.4), 1.97 (br s, 1H, OH), 1.60–1.25 (m, 6H); δC (75 MHz,
CDCl3) 188.1, 166.1, 155.6, 141.9, 137.0, 135.8, 134.4, 131.4,
131.1, 129.9 and 129.5, 128.1 and 128.0, 125.4, 81.8, 72.4, 52.8,
35.4, 30.9, 29.4, 25.6; m/z (Cl/NH3) 504 and 502 [M ϩ NH4]ϩ,
487 and 485 [M ϩ H]ϩ.
(cmϪ1, CDCl ) 3406 (OH), 1718 (C᎐O); δ (250 MHz, CDCl3)
᎐
3
H
7.41 (s, 1H), 7.30–7.14 (m, 5H, arom-H), 6.75 (d, 1H, J 7.8),
5.40 (br s, 1H, OH), 4.73 (dd, 1H, J 7.8 and 4.3), 3.93 (dd, 1H,
J 2 and 10), 3.81 (dt, 1H, J 4.3 and 6.5), 3.63 (s, 3H, COOMe),
2.59 (t, 2H, J 6), 2.35 (m, 2H), 1.72–1.16 (m, 10H); δC (62.5
MHz, CDCl3) 188.7, 175.1, 157.75, 142.3, 138.3, 134.8, 128.7,
128.3, 128.2, 125.6, 81.5, 75.3, 73.3, 70.4, 51.8, 35.7, 33.3, 32.0,
31.2, 31.1, 26.1, 20.3; m/z (Cl/NH3) 530 and 528 [M ϩ NH4]ϩ.
(Z ) and (E )-4-[8-Bromo-2,2-dimethyl-7-oxo-4(R)-(4-phenyl-
butyl)-1,3-dioxa-spiro[4.4]-5(S )non-8-en-6-(Z )-ylidenemethyl]-
benzoic acid methyl ester (41) and (42)
20
Compound 35. [α]D ϩ6 (c 1, CHCl3); νmax (cmϪ1, CDCl3)
3445 (OH), 1723 (C᎐O); δ (250 MHz, CDCl3) 7.41 (s, 1H),
᎐
H
7.30–7.15 (m, 5H, arom-H), 6.64 (d, 1H, J 7.1), 4.77 (dd, 1H,
J 7.1 and 6.9), 4.73 (br s, 1H, OH), 4.52 (br s, 1H, OH), 4.44 (m,
1H), 3.96 (dd, 1H, J 2, J 10), 3.40 (br s, 1H, OH), 2.60 (m, 2H),
2.53 (m, 2H), 2.11–1.51 (m, 10H); δC (62.5 MHz, CDCl3) 188.1,
171.5, 156.8, 142, 138.7, 132.8, 128.9, 128.0, 125.4, 82.2, 81.4,
75.0, 69.2, 35.4, 30.7, 30.1, 29.4, 25.6, 22.9, 17.7; m/z (Cl/NH3)
498 and 496 [M ϩ NH4]ϩ. HRMS. Calc for M- C11H14O:
315.99463, found 315.99442.
Obtained in 43% overall yield from compound (4R, 5S) 22 (130
mg, 0.34 mmol) by the aldolisation/elimination sequence with
aldehyde 36, following the same procedure as for compound 20.
Compounds 41 (Z ) ؉ 42 (E ). δH (300 MHz, CDCl3) 8.10 and
8.00 (2m, 4H, arom-H), 7.78 (s, 0.5H), 7.64 (s, 0.5H, 7.46 (s,
0.5H), 7.28–7.06 (m, 5H, arom-H), 7.00 (s, 1H), 4.14 (dd, 1H),
3.97 (dd, 1H), 3.95 (s, 1.5H, COOMe), 3.94 (s, 1.5H, COOMe),
2.57 (t, 2H), 2.49 (t, 1H), 1.59, 1.58, 1.54, 1.30 (4s, 6H, 1.64–
1.18 (m, 6H); δC (75 MHz, CDCl3) 187.5, 185.6, 166.3, 155.3,
152.4, 141.9, 141.9, 138.1, 137.7, 137.4, 137.0, 132.4, 131.4,
131.0, 130.9, 130.7, 129.8, 129.4, 129.2, 128.5, 128,2, 125.7,
109.7, 109.2, 87.4, 86.9, 82.9, 78.8, 52.2, 35.6, 35.4, 31.0, 30.8,
29.6, 29.3, 29.2, 28.6, 27.1, 26.5, 25.9, 25.5; m/z (DCI/NH3) 542
and 544 [M ϩ NH4]ϩ, 527 and 525 [M ϩ H]ϩ.
4-[8-Bromo-2,2-dimethyl-7-oxo-4(R)-(4-phenyl-butyl)-1,3-
dioxa-spiro[4.4]-5(S )non-8-en-6-(Z )-ylidenemethyl]-benzoic
acid methyl ester (37)
Treatment of compound 20 (120 mg, 0.32 mmol) following the
same procedure as for compound 29, with the aldehyde 36
furnished the intermediary, not characterized aldol (12 mg,
70%). The latter compound was treated with Ac2O (2.5 mL)
and pyridine (10 mL) and 4-DMAP for 1.5 h at 80 ЊC. After
evaporation and purification of the residue by flash column
chromatography, a Z/E mixture of compounds 37 ϩ 38 was
obtained (10/1 ratio, 70 mg, 61%). A second purification
allowed isolation of pure compound 37.
4(Z ) and 4(E )-[4-Bromo-2(R)-hydroxy-2-(1(R)-hydroxy-5-
phenyl-pentyl)-5-oxo-cyclopent-3-enylidenemethyl]-benzoic acid
methyl ester (43) and (44)
Obtained by hydrolysis of the mixture 41 ϩ 42 (50 mg, 0.95
mmol) using the same condition as for compounds 37 ϩ 38 and
furnished 43 (Z) (22 mg, 48%) and 44 (E) (21 mg, 46%).
20
Major compound (Z ) 37. [α]D Ϫ38 (c 0.66, CHCl3); Found
C, 64.21; H, 5.89. Calc. for C28H29O5 Br M 525.44 C24H31O7Br
(511.41) C, 64.01; H, 5.56%; νmax (cmϪ1, CDCl ) 1718 (C᎐O
Compound (Z ) 43. [α]D20 ϩ5 (c 1, CHCl3); Found C, 61.74; H,
5.27. Calc. for C25H25O5Br (485.38): C, 61.86; H, 5.19%; νmax
(cmϪ1, CDCl ) 3850 (OH), 1718 (C᎐O conj.), 1627 (C᎐O ester);
᎐
3
conjugate), 1631 (C᎐O ester); δH (250 MHz, CDCl3) 8.05 (br d,
᎐
2H, J 8.4), 7.98 (br d, 2H, J 8.4), 7.35 (s, 1H), 7.26–7.10 (m, 5H,
arom-H), 6.96 (s, 1H), 4.22 (dd, 1H, J 2.4 and J 9), 3.93 (s, 3H,
᎐
᎐
3
δH (300 MHz, CDCl3) 8.10 (br d, 2H, J 8.5), 8.00 (br d, 2H,
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 2 0 2 8 – 2 0 3 9
2035