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DOI: 10.1055/s-0029-1219810
Stereoselective Synthesis of (-)-Pironetin by an Iterative Prins Cyclisation and Reductive Cleavage Strategy
Publication History
Publication Date:
09 April 2010 (online)
Abstract
A stereoselective synthesis of pironetin, a natural product which is highly immunosuppressive and shows remarkable plant growth regulatory and antitumoral activities, is described. The approach avails successfully the high stereoselection of Prins cyclisation. The route relies, in addition, on the reductive opening of cyclic ethers, olefin metathesis, and lithium acetylide displacement of tosylate.
Key words
natural products - Prins cyclisation - stereoselective synthesis - reductive cleavage - olefin metathesis
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References and Notes
Spectroscopic
and Physical Data of Selected Compounds(2
R
,3
S
,4
R
,6
R
)-2-[(
S
)-1-(Benzyloxy)propan-2-yl]-tetra-hydro-6-hydroxymethyl)-3-methyl-2
H
-pyran-4-ol
(5)
[α]D
²5 +18.5
(c 1.0, CHCl3); R
f
= 0.3
(SiO2, 60% EtOAc in hexane). IR (neat): 3390,
2926, 2859, 1359, 1158, cm-¹. ¹H NMR
(300 MHz, CDCl3): δ = 7.23-7.30
(m, 5 H), 4.39-4.55 (m, 2 H), 3.21-3.56 (m, 7
H), 2.02-2.11 (m, 1 H), 1.77-1.86 (m, 1 H), 1.22-1.44
(m, 2 H), 0.96 (d, 3 H, J = 6.64
Hz), 0.85 (d, 3 H, J = 6.64
Hz). ¹³C NMR (75 MHz, CDCl3): δ = 138.53,
128.30, 127.48, 79.47, 75.50, 73.33, 73.12, 72.97, 65.83, 40.40,
36.77, 34.10, 12.04, 9.54. ESI-HRMS: m/z
[M + Na]+ calcd
for C17H26NaO4: 317.1728; found: 317.1719.
(2
S
,3
R
,4
R
,5
R
)-1-(Benzyloxy)-5-(
tert
-butyldimethyl-silyloxy)-2,4-dimethyloct-7-en-3-ol
(10)
[α]D
²5 +13.9
(c 0.65, CHCl3); R
f
= 0.6
(SiO2, 10% EtOAc in hexane). IR (neat): 3500,
2930, 2855, 1461, 1063, 911 cm-¹. ¹H
NMR (300 MHz, CDCl3): δ = 7.30-7.27
(m, 5 H), 5.81-5.67 (m, 1 H), 5.08-4.49 (m, 2
H), 4.45-4.56 (m, 2 H), 3.97-3.92 (m, 1 H), 3.75
(d, 1 H, J = 9.82
Hz), 3.53-3.39 (m, 2 H), 2.37-2.20 (m, 2 H), 1.85-1.70
(m, 2 H), 1.46 (br, OH), 0.89-0.87 (m, 12 H), 0.75 (d,
3 H, J = 6.8
Hz), 0.06 (s, 3 H), 0.09 (s, 3 H). ¹³C
NMR (75 MHz, CDCl3): δ = 138.60, 135.13, 128.24,
127.47, 127.36, 116.90, 116.67, 81.09, 73.86, 72.82, 71.15, 60.70,
40.55, 39.38, 35.30, 26.02, 18.2, 9.7, 9.1,
-3.17, -4.37.
ESI-HRMS: m/z [M + Na]+calcd
for C23H40NaO3Si: 415.2644; found:
415.4635.
(3
E
,6
R
,7
S
,8
R
,9
S
,11
E
)-8-Methoxy-7,9-dimethyltridec-3,11-dien-6-ol
(4)
[α]D
²5 +4.0
(c 1.3, CHCl3); R
f
= 0.5
(SiO2, 20% EtOAc in hexane); IR (neat): 3420,
2966, 2931, 1715, 1457, 1083, 971 cm-¹; ¹H
NMR (300 MHz, CDCl3): δ = 5.62-5.29
(m, 4 H), 3.90-3.83 (m, 1 H), 3.48 (s, 3 H), 2.98 (m, 1
H), 2.57 (br, 1 H, OH), 2.27-1.75 (m, 8 H), 1.67 (d, 3
H, J = 6.40
Hz), 0.98 (t, 3 H, J = 7.34
Hz), 0.92 (d, 3 H, J = 7.9
Hz), 0.89 (d, 3 H, J = 7.8
Hz). ¹³C NMR (75 MHz, CDCl3): δ = 134.69,
129.18, 126.58, 125.63, 89.80, 70.6, 61.63, 38.10, 37.8, 37.2, 36.05, 25.63,
17.93, 14.57, 13.8, 10.91. ESI-HRMS: m/z [M + Na]+calcd
for C16H30NaO2: 277.1987; found:
277.1977.
(2
R
,3
S
,4
R
,6
R
)-3-Ethyl-tetrahydro-6-[(
E
,2
S
,3
R
,4
S
)-3-methoxy-4-methyloct-6-en-2-yl]-2-vinyl-2
H
-pyran-4-ol (3a)
[α]D
²5 -27.6
(c 0.65, CHCl3). IR (neat):
3427, 2967, 2929, 1718, 1457, 1089, 759 cm-¹. ¹H
NMR (300 MHz, CDCl3):
δ = 5.88-5.71
(m, 1 H), 5.49-5.36 (m, 2 H), 5.26-5.11 (m, 2 H),
3.69-3.45 (m, 3 H), 3.33 (s, 3 H), 3.05 (dd, 1 H, J = 9.55, 2.94
Hz), 2.32-2.27 (m, 1 H), 2.08-1.95 (m, 2 H), 1.76-1.41 (m,
7 H), 1.25-1.14 (m, 1 H), 1.02-0.75 (m, 11 H). ¹³C
NMR (75 MHz, CDCl3): δ = 130.65, 130.44,
128.71, 126.13, 84.8, 80.25, 74.34, 73.43, 70.67, 50.97, 49.21,
40.54, 38.99, 38.25, 35.49, 19.41, 17.96, 11.86, 10.18. ESI-HRMS: m/z [M + Na]+ calcd
for C19H34NaO3: 333.2405; found: 333.2409.
(4
R
,5
R
,7
R
,8
S
,9
R
,10
S
,12
E
)-4-Ethyl-9-methoxy-5-(methoxymethoxy)-8,10-dimethyltetradeca-2,12-dien-7-yl
acetate (17)
IR (neat): 2929, 2855, 1740, 1244, 1097,
966 cm-¹. ¹H NMR (300
MHz, CDCl3): δ = 5.51-5.03
(m, 5 H), 4.63-4.59 (m, 2 H), 3.56-3.41 (m, 1
H), 3.39 (s, 3 H), 3.37 (s, 3 H), 2.84-2.77 (m, 1 H), 2.03
(s, 3 H), 2.17-1.91 (m, 3 H), 1.66 (d, 6 H, J = 5.28 Hz),
1.75-1.50 (m, 4 H), 1.45-1.28 (m, 2 H), 0.92-0.79
(m, 9 H). ¹³C NMR (75 MHz, CDCl3): δ = 170.40, 134.51,
132.50, 125.50, 125.5, 96.30, 88.51, 66.99, 68.30, 58.0, 55.62,
49.06, 39.52, 36.42, 35.50, 33.75, 23.65, 21.20, 19.53, 19.35, 15.30,
12.42, 10.25. ESI-HRMS: m/z [M + Na]+ calcd
for C23H24NaO5: 421.2929; found:
421.2923.
(5
R
,6
R
)-5-Ethyl-5,6-dihydro-6-[(
E
,2
R
,3
S
,4
R
,5
S
)-2-hydroxy-4-methoxy-3,5-dimethylnon-7-enyl]pyran-2-one
(1)
[α]D
²5 -139.5
(c 0.35, CHCl3); R
f
= 0.3
(SiO2, 50% EtOAc in hexane); IR (neat): 3479,
2965, 2931, 1718, 1459, 1384, 1088 cm-¹. ¹H
NMR (300 MHz, CDCl3): δ = 7.04 (dd,
1 H, J = 9.82,
6.04 Hz), 6.04 (d, 1 H, J = 9.82
Hz), 5.50-5.32 (m, 2 H), 4.76 (m, 1 H), 4.23 (br d, 1 H),
3.47 (s, 3 H), 3.39 (br, OH), 2.36-2.27 (m, 1 H), 3.00-2.97
(m, 1 H), 2.13-2.06 (m, 1 H), 1.97-1.63 (m, 6
H), 1.67 (d, 3 H, J = 5.27
Hz), 1.56-1.45 (m, 1 H), 1.01 (t, 3 H, J = 7.18
Hz), 0.97 (d, 3 H, J = 7.18
Hz), 0.95 (d, 3 H, J = 6.70
Hz). ¹³C NMR (75 MHz, CDCl3): δ = 164.1,
144.8, 121.5, 96.1, 75.2, 69.7, 55.4, 41.8, 29.4, 20.1.164.75, 150.77,
130.08, 126.91, 120.72, 90.2, 77.73, 67.17, 61.55, 39.16, 39.05,
37.32, 36.73, 35.96, 20.76, 17.91, 15.1, 11.88, 10.96. ESI-HRMS: m/z [M + Na]+ calcd
for C19H32NaO4 347.2198; found:
347.2205.