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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)
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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
-
1a
Kobayashi S.Tsuchiya K.Harada T.Nishide M.Kurokawa T.Nakagawa T.Shimada N.Kobayashi K.
J. Antibiot. 1994, 47: 697 -
1b
Kobayashi S.Tsuchiya K.Kurokawa T.Nakagawa T.Shimada N.Iitaka Y.
J. Antibiot. 1994, 47: 703 -
1c
Tsuchiya K.Kobayashi S.Harada T.Nishikiori T.Nakagawa T.Tatsuta K.
J. Antibiot. 1997, 50: 259 - 2
Konodoh M.Usui T.Kobayashi S.Tsuchiya K.Nishikawa K.Nishikiori T.Mayumi T.Osada H. Cancer Lett. 1998, 126: 29 - 3 For a paper about chemical modifications
of pironetin to reduce its toxicity, see:
Yasui K.Tamura Y.Nakatani T.Horibe I.Kawada K.Koizumi K.Suzuki R.Ohtani M. J. Antibiot. 1996, 49: 173 - For examples of the Prins cyclisation, see:
-
4a
Barry CStJ.Crosby SR.Harding JR.Hughes RA.King CD.Parker GD.Willis CL. Org. Lett. 2003, 5: 2429 -
4b
Yang X.-F.Mague JT.Li C.-J. J. Org. Chem. 2001, 66: 739 -
4c
Aubele DL.Wan S.Floreancig PE. Angew. Chem. Int. Ed. 2005, 44: 3485 -
4d
Barry CS.Bushby N.Harding JR.Willis CS. Org. Lett. 2005, 7: 2683 -
4e
Cossey KN.Funk RL. J. Am. Chem. Soc. 2004, 126: 12216 -
4f
Crosby SR.Harding JR.King CD.Parker GD.Willis CL. Org. Lett. 2002, 4: 3407 -
4g
Marumoto S.Jaber JJ.Vitale JP.Rychnovsky SD. Org. Lett. 2002, 4: 3919 -
4h
Kozmin SA. Org. Lett. 2001, 3: 755 -
4i
Jaber JJ.Mitsui K.Rychnovsky SD. J. Org. Chem. 2001, 66: 4679 -
4j
Kopecky DJ.Rychnovsky SD.
J. Am. Chem. Soc. 2001, 123: 8420 -
4k
Rychnovsky SD.Thomas CR. Org. Lett. 2000, 2: 1217 -
4l
Rychnovsky SD.Yang G.Hu Y.Khire UR. J. Org. Chem. 1997, 62: 3022 -
4m
Su Q.Panek JS. J. Am. Chem. Soc. 2004, 126: 2425 -
4n
Yadav JS.Reddy BVS.Sekhar KC.Gunasekar D. Synthesis 2001, 885 -
4o
Yadav JS.Reddy BVS.Reddy MS.Niranjan N. J. Mol. Catal. A: Chem. 2004, 210: 99 -
4p
Yadav JS.Reddy BVS.Reddy MS.Niranjan N.Prasad AR. Eur. J. Org. Chem. 2003, 1779 - For our previous applications of Prins cyclisation, see:
-
5a
Yadav JS.Reddy MS.Rao PP.Prasad AR. Tetrahedron Lett. 2006, 47: 4397 -
5b
Yadav JS.Reddy MS.Prasad AR. Tetrahedron Lett. 2006, 47: 4937 -
5c
Yadav JS.Reddy MS.Prasad AR. Tetrahedron Lett. 2005, 46: 2133 -
5d
Yadav JS.Reddy MS.Prasad AR. Tetrahedron Lett. 2006, 47: 4995 -
5e
Yadav JS.Reddy MS.Rao PP.Prasad AR. Synlett 2007, 2049 -
5f
Yadav JS.Rao PP.Reddy MS.Rao NV.Prasad AR. Tetrahedron Lett. 2007, 48: 1469 -
5g
Yadav JS.Kumar NN.Reddy MS.Prasad AR. Tetrahedron 2006, 63: 2689 -
5h
Yadav JS.Kumar Rao PP.Reddy MS.Prasad AR. Tetrahedron Lett. 2008, 49: 5427 - As shown below, compound 10 was subjected to TBS ether cleavage and then transformed to the corresponding acetonide to confirm the anti relationship of hydroxyl groups by examination of the ¹³C NMR spectrum. See:
-
6a
Rychnovsky SD.Skalitzky DJ. Tetrahedron Lett. 1990, 31: 945 -
6b
Evans DA.Rieger DL.Gage JR. Tetrahedron Lett. 1990, 39: 7099 ; One broad coupling (J = 9.0 Hz) of 3-H of the acetonide in Scheme 3 in its ¹H NMR supported the stereochemistry of the 4-α-methyl group - 7
Nicolaou KC.Koftis TV.Vyskocil S.Petrovic G.Ling T.Yamada YMA.Tang W.Frederick MO. Angew. Chem. Int. Ed. 2004, 43: 4318 -
8a
Toshima K.Jyojima T.Miyamoto N.Katohno M.Nakata M.Mastumura S. J. Org. Chem. 2001, 66: 1708 -
8b
Moune S.Niel G.Busquet M.Eggleston I.Jouin P. J. Org. Chem. 1997, 62: 3332 - 9
Imoto H.Matsumoto M.Odaka H.Sakamoto J.Kimura H.Nonaka M.Kiyota Y.Momose Y. Chem. Pharm. Bull. 2004, 52: 120 -
10a
Scholl S.Ding S.Lee CW.Grubbs RH. Org. Lett. 1999, 1: 953 -
10b
Sanford MS.Love JA.Grubbs RH. J. Am. Chem. Soc. 2001, 123: 6543 -
10c
Shibahara S.Fujino M.Tashiro Y.Takahashi K.Ishihara J.Hatakeyama S. Org. Lett. 2008, 10: 2139 -
10d
Schwab P.France MB.Ziller JW.Grubbs RH. Angew. Chem., Int. Ed. Engl. 1995, 34: 2039 ; Angew. Chem. 1995, 107, 2179
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.