M. Daoubi et al. / Tetrahedron 65 (2009) 4834–4840
4839
(s, C-6), 142.1 (d, C-4), 136.1, 135.4, 129.1, 128.7, 128.7, 128.5, 127.4,
127.1 (8d, Benzyl-MPA), 115.4 (d, C-3), 102.7 (d, C-5), 82.5, 81.9 (2d,
CH-MPA), 72.3 (d, C-10), 72.1 (d, C-20), 57.3 (s, OMe), 57.2 (s, OMe),
32.1 (t, C-30), 17.8 (t, C-40), 13.4 (q, C-50) ppm. MS: m/z¼494 (5), 404
(33), 292 (87), 268 (41), 218 (35), 230 (52), 130 (100), 95 (14), 71
(45). HRMS calcd. for C28H30O8: 494.1940; found: 494.1947 [M]þ.
126.8 (8d, Benzyl-MPA), 115.7 (d, C-3), 104.3 (d, C-5), 82.1, 81.9 (2d,
CH-MPA), 72.2 (d, C-10), 71.7 (d, C-20), 57.3 (s, OMe), 57.2 (s, OMe),
30.8 (t, C-30), 17.2 (t, C-40), 13.1 (q, C-50) ppm. HRMS calcd. for
C28H30O8: 494.1940; found: 494.1950 [M]þ.
4.11.6. Bis-(R)-MPA ester of 6-[(10R,20R)-dihydroxypentyl]-2H-
pyran-2-one (15a)
25
4.11.2. Bis-(R)-MPA ester of 6-[(10S,20R)-dihydroxypentyl]-2H-
pyran-2-one (13a)
[a
]
þ14.8 (c 0.26, MeOH). IR (film): nmax¼1744, 1638, 1560,
D
1168, 1104, 805 cmꢀ1. 1H NMR (400 MHz, CDCl3):
d
¼7.25–7.36 (m,
25
[
a]
ꢀ117.6 (c 0.28, MeOH). IR (film): nmax¼1751, 1639, 1560,
10H, ArH), 6.76 (dd, J¼6.4, 9.2 Hz, 1H, 4-H), 6.00 (d, J¼9.2 Hz, 1H,
3-H), 5.41 (d, J¼4.6 Hz, 1H, 10-H), 5.36 (dt, J¼4.6, 6.4 Hz, 1H, 20-H),
5.04 (d, J¼6.4 Hz, 1H, 5-H), 4.67 (s, 1H, MPA-H), 4.62 (s, 1H, MPA-H),
3.37 (s, 3H, OMe), 3.33 (s, 3H, OMe), 1.56 (m, J¼7.4, 6.4 Hz, 2H, 30-H),
1.22–1.33 (m, 2H, H-40), 0.86 (t, J¼7.3 Hz, 3H, 50-H) ppm. 13C NMR
D
1165, 1112, 804 cmꢀ1. 1H NMR (400 MHz, CDCl3):
d
¼7.34–7.46 (m,
10H, ArH), 6.70 (dd, J¼6.7, 9.2 Hz, 1H, 4-H), 5.97 (d, J¼9.2 Hz, 1H,
3-H), 5.39 (d, J¼2.6 Hz, 1H, 10-H), 5.24 (ddd, J¼2.6, 4.6, 8.7 Hz,
1H, 20-H), 5.12 (d, J¼6.7 Hz, 1H, 5-H), 4.78 (s, 1H, MPA-H), 4.62
(s, 1H, MPA-H), 3.38 (s, 3H, OMe), 3.29 (s, 3H, OMe), 1.08–1.26
(m, 2H, 30-H), 1.10 (m, 2H, 40-H), 0.69 (t, J¼7.0 Hz, 3H, 50-H) ppm. 13C
(100 MHz, CDCl3):
d
¼169.6 (s, CO-MPA), 168.7 (s, CO-MPA), 160.4 (s,
C-2), 157.6 (s, C-6), 142.3 (d, C-4), 136.0, 135.3, 128.8, 128.7, 128.6,
127.3, 127.1 (8d, Benzyl-MPA), 115.2 (d, C-3), 103.7 (d, C-5), 82.1, 81.8
(2d, CH-MPA), 72.4 (d, C-10), 72.1 (d, C-20), 57.4 (s, OMe), 57.2 (s,
OMe), 31.9 (t, C-30), 18.3 (t, C-40), 13.5 (q, C-50) ppm. HRMS calcd. for
C28H30O8: 494.1940; found: 494.1923 [M]þ.
NMR (100 MHz, CDCl3):
d¼169.3 (s, CO-MPA), 169.1 (s, CO-MPA),
160.5 (s, C-2), 158.0 (s, C-6), 142.2 (d, C-4), 136.3, 135.5, 129.1, 128.7,
128.6, 128.4, 127.3, 127.1 (8d, Benzyl-MPA), 114.9 (d, C-3), 102.3
(d, C-5), 82.1, 81.9 (2d, CH-MPA), 72.1 (d, C-10), 71.6 (d, C-20), 57.3
(s, OMe), 57.2 (s, OMe), 32.0 (t, C-30),18.2 (t, C-40),13.4 (q, C-50) ppm.
HRMS calcd. for C28H30O8: 494.1940; found: 494.1988 [M]þ.
4.11.7. Bis-(S)-MPA ester of 6-[(10S,20S)-dihydroxypentyl]-2H-
pyran-2-one (14b)
25
4.11.3. Bis-(S)-MPA ester of 6-[(10R,20S)-dihydroxypentyl]-2H-
pyran-2-one (12b)
[a
]
ꢀ13.4 (c 0.26, MeOH). IR (film): nmax¼1744, 1638, 1560,
D
1169, 1105, 805 cmꢀ1. 1H NMR (400 MHz, CDCl3):
d
¼7.26–7.37 (m,
25
[
a]
þ120.5 (c 0.19, MeOH). IR (film): nmax¼1748, 1643, 1560,
10H, ArH), 6.76 (dd, J¼6.7, 9.2 Hz, 1H, 4-H), 6.01 (d, J¼9.2 Hz, 1H,
3-H), 5.41 (d, J¼4.6 Hz, 1H, 10-H), 5.37 (dt, J¼4.6, 6.4 Hz, 1H, 20-H),
5.05 (d, J¼6.7 Hz, 1H, 5-H), 4.68 (s, 1H, MPA-H), 4.64 (s, 1H, MPA-H),
3.39 (s, 3H, OMe), 3.35 (s, 3H, OMe),1.58 (m, J¼7.4, 6.4 Hz, 2H, 30-H),
1.22–1.33 (m, 2H, 40-H), 0.87 (t, J¼7.3 Hz, 3H, 50-H) ppm. 13C NMR
D
1165, 1106, 803 cmꢀ1. 1H NMR (400 MHz, CDCl3):
d¼7.34–7.46 (m,
10H, ArH), 6.70 (dd, J¼6.7, 9.2 Hz, 1H, 4-H), 5.97 (d, J¼9.2 Hz, 1H,
3-H), 5.40 (d, J¼2.6 Hz, 1H, 10-H), 5.24 (ddd, J¼2.6, 4.6, 8.7 Hz,
1H, 20-H), 5.12 (d, J¼6.7 Hz, 1H, 5-H), 4.78 (s, 1H, MPA-H), 4.62
(s, 1H, MPA-H), 3.38 (s, 3H, OMe), 3.29 (s, 3H, OMe), 1.08–1.26
(m, 2H, 30-H), 1.10 (m, 2H, 40-H), 0.69 (t, J¼7.0 Hz, 3H, 50-H) ppm. 13C
(100 MHz, CDCl3):
d
¼169.4 (s, CO-MPA), 168.6 (s, CO-MPA), 160.2 (s,
C-2), 157.4 (s, C-6), 142.2 (d, C-4), 135.9, 135.1, 128.7, 128.6, 128.4,
127.2, 127.0 (8d, Benzyl-MPA), 115.0 (d, C-3), 103.6 (d, C-5), 82.0,
81.7 (2d, CH-MPA), 72.2 (d, C-10), 72.0 (d, C-20), 57.2 (s, OMe), 57.0 (s,
OMe), 31.7 (t, C-30), 18.1 (t, C-40), 13.3 (q, C-50) ppm. HRMS calcd. for
C28H30O8: 494.1940; found: 494.1953 [M]þ.
NMR (100 MHz, CDCl3):
d¼169.3 (s, CO-MPA), 169.1 (s, CO-MPA),
160.5 (s, C-2), 158.0 (s, C-6), 142.2 (d, C-4), 136.3, 135.5, 129.1, 128.7,
128.6, 128.4, 127.3, 127.1 (8d, Benzyl-MPA), 114.9 (d, C-3), 102.3
(d, C-5), 82.1, 81.9 (2d, CH-MPA), 72.1 (d, C-10), 71.6 (d, C-20), 57.3
(s, OMe), 57.2 (s, OMe), 32.0 (t, C-30),18.2 (t, C-40),13.4 (q, C-50) ppm.
HRMS calcd. for C28H30O8: 494.1940; found: 494.1956 [M]þ.
4.11.8. Bis-(S)-MPA ester of 6-[(10R,20R)-dihydroxypentyl]-2H-
pyran-2-one (15b)
25
4.11.4. Bis-(S)-MPA ester of 6-[(10S,20R)-dihydroxypentyl]-2H-
pyran-2-one (13b)
[a
]
þ96.1 (c 0.22, MeOH). IR (film): nmax¼1748, 1644, 1562,
D
1166, 1113, 806 cmꢀ1. 1H NMR (400 MHz, CDCl3):
d
¼7.28–7.44 (m,
25
[
a]
ꢀ12.4 (c 0.24, MeOH). IR (film): nmax¼1747, 1642, 1560,
10H, ArH), 7.10 (dd, J¼6.5, 9.3 Hz, 1H, H-4), 6.17 (d, J¼9.3 Hz, 1H,
H-3), 5.98 (d, J¼6.5 Hz, 1H, H-5), 5.52 (d, J¼6.4 Hz, 1H, H-10), 5.15
(ddd, J¼3.6, 6.4, 9.5 Hz, 1H, H-20), 4.80 (s, 1H, H-MPA), 4.53 (s, 1H,
H-MPA), 3.38 (s, 3H, OMe), 3.34 (s, 3H, OMe), 1.02–1.17 (m, 2H,
H-30), 0.74 (m, 2H, H-40), 0.49 (t, J¼7.3 Hz, 3H, H-50) ppm. 13C NMR
D
1167, 1113, 805 cmꢀ1
.
1H NMR (400 MHz, CDCl3):
d¼7.30–7.42 (m,
10H, ArH), 6.76 (dd, J¼6.5, 9.5 Hz, 1H, 4-H), 6.02 (d, J¼9.5 Hz, 1H,
3-H), 5.49 (d, J¼4.6 Hz, 1H, 10-H), 5.30 (dt, J¼4.6, 9.0 Hz, 1H, 20-H),
5.17 (d, J¼6.5 Hz, 1H, 5-H), 4.76 (s, 1H, MPA-H), 4.66 (s, 1H, MPA-H),
3.39 (s, 3H, OMe), 3.35 (s, 3H, OMe), 1.28–1.49 (m, 2H, 30-H), 0.94–
1.04 (m, 2H, 40-H), 0.69 (t, J¼7.3 Hz, 3H, 50-H) ppm. 13C NMR
(100 MHz, CDCl3):
d
¼169.4 (s, CO-MPA), 169.0 (s, CO-MPA), 160.5 (s,
C-2), 158.0 (s, C-6), 142.4 (d, C-4), 135.8, 135.4, 128.9, 128.6, 128.5,
128.3, 127.1, 126.8 (8d, Benzyl-MPA), 115.7 (d, C-3), 104.3 (d, C-5),
82.1, 81.9 (2d, CH-MPA), 72.2 (d, C-10), 71.7 (d, C-20), 57.3 (s, OMe),
57.2 (s, OMe), 30.8 (t, C-30), 17.2 (t, C-40), 13.1 (q, C-50) ppm. HRMS
calcd. for C28H30O8: 494.1940; found: 494.1950 [M]þ.
(100 MHz, CDCl3)
d
¼169.7 (s, CO-MPA), 169.0 (s, CO-MPA), 160.4 (s,
C-2), 158.2 (s, C-6), 142.1 (d, C-4), 136.1, 135.4, 129.1, 128.7, 128.7,
128.5, 127.4, 127.1 (8d, Benzyl-MPA), 115.4 (d, C-5), 102.7 (d, C-3),
82.5, 81.9 (2d, CH-MPA), 72.3 (d, C-10), 72.1 (d, C-20), 57.3 (s, OMe),
57.2 (s, OMe), 32.1 (t, C-30), 17.8 (t, C-40), 13.4 (q, C-50) ppm. HRMS
calcd. for C28H30O8: 494.1940; found: 494.1946 [M]þ.
4.12. Hydrolysis of Mosher’s esters: general procedure
4.11.5. Bis-(R)-MPA ester of 6-[(10S,20S)-dihydroxypentyl]-2H-
pyran-2-one (14a)
The corresponding Mosher’s ester (10 mg, 0.02 mmol) was
dissolved in methanol (5 mL). Then three drops of an aqueous
solution of K2CO3 (6.1 mg, 0.044 mmol) were added and the mix-
ture was stirred at room temperature for 3 min. The reaction
mixture was directly chromatographed on flash chromatography
column (silica gel, hexane/ethyl acetate 2:3) to yield the desired
25
[
a]
ꢀ97.9 (c 0.24, MeOH). IR (film): nmax¼1750, 1641, 1560,
D
1165, 1107, 805 cmꢀ1. 1H NMR (400 MHz, CDCl3):
d
¼7.26–7.44 (m,
10H, ArH), 7.10 (dd, J¼6.5, 9.3 Hz, 1H, 4-H), 6.16 (d, J¼9.3 Hz, 1H, 3-
H), 5.97 (d, J¼6.5 Hz,1H, 5-H), 5.52 (d, J¼6.4 Hz,1H,10-H), 5.15 (ddd,
J¼3.6, 6.4, 9.5 Hz,1H, 20-H), 4.79 (s,1H, MPA-H), 4.51 (s,1H, MPA-H),
3.37 (s, 3H, OMe), 3.33 (s, 3H, OMe),1.01–1.18 (m, 2H, 30-H), 0.73 (m,
2H, 40-H), 0.48 (t, J¼7.3 Hz, 3H, 50-H) ppm. 13C NMR (100 MHz,
product 6-[(10R,20S)-dihydroxypentyl]-2H-pyran-2-one (12) (76%),
25
[a
]
þ120.6 (c 0.15, MeOH); 6-[(10S,20R)-dihydroxypentyl]-2H-py-
D
25
CDCl3):
d
¼169.4 (s, CO-MPA), 169.0 (s, CO-MPA),160.5 (s, C-2),158.0
ran-2-one (13) (75%), [
a
]
ꢀ123.1 (c 0.1, MeOH); 6-[(10S,20S)-
D
25
(s, C-6), 142.4 (d, C-4), 135.8, 135.4, 128.9, 128.6, 128.5, 128.3, 127.1,
dihydroxypentyl]-2H-pyran-2-one (14) (80%), [
a
]
ꢀ79.6 (c 0.5,
D