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Synlett 2010(8): 1205-1208  
DOI: 10.1055/s-0029-1219810
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Stereoselective Synthesis of (-)-Pironetin by an Iterative Prins Cyclisation and Reductive Cleavage Strategy

J. S. Yadav*, Hissana Ather, N. Venkateswar Rao, M. Sridhar Reddy, A. R. Prasad
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad-500 007, India
Fax: +91(40)27160512; e-Mail: yadavpub@iict.res.in;
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Publikationsverlauf

Received 17 December 2009
Publikationsdatum:
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

    References and Notes

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11

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.