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Stayton, M. M. Tetrahedron Lett. 1993, 34, 223–226; (b) Midland, S. L.; Keen, N.
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131–139.
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1994, 7, 148–150; (b) Keen, N.; Midland, S. L.; Boyd, C.; Yucel, I.; Tsurushima, T.;
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teractions; Daniels, M. J., Downie, J. A., Osburn, A. E., Eds.; Kluwer Academic:
Boston, MA, 1994; Vol. 3, pp 41–48.
9. Wood, J. L.; Jeong, S.; Salcedo, A.; Jenkins, J. J. Org. Chem. 1995, 60, 286–287.
10. (a) Kuwahara, S.; Moriguchi, M.; Miyagawa, K.; Konno, M.; Kodama, O. Tetra-
hedron Lett. 1995, 36, 3201–3202; (b) Kuwahara, S.; Moriguchi, M.; Miyagawa,
K.; Konno, M.; Kodama, O. Tetrahedron 1995, 51, 8809–8814; (c) Ishihara, I.;
Sugimoto, T.; Murai, A. Synlett 1996, 335–336; (d) Ishihara, I.; Sugimoto, T.;
Murai, A. Tetrahedron 1997, 53, 16029–16040; (e) Henschke, J. P.; Rickards, R. W.
Tetrahedron Lett. 1996, 37, 3557–3560; (f) Henschke, J. P.; Rickards, R. W. J.
Labelled Compd. Radiopharm. 1998, 41, 211–220; (g) Honda, T.; Mizutani, H.;
Kanai, K. J. Org. Chem. 1996, 61, 9374–9378; (h) Zeng, C.-M.; Midland, S. L.; Keen,
N. T.; Sims, J. J. J. Org. Chem. 1997, 62, 4780–4784; (i) Yu, P.; Wang, Q.-G.; Mak, T.
C. W.; Wong, H. N. C. Tetrahedron 1998, 54, 1783–1788; (j) Wong, H. N. C. Chin. J.
Chem. 2005, 23, 1106–1108; (k) Cheˆnevert, R.; Dasser, M. Can. J. Chem. 2000, 78,
275–279; (l) Cheˆnevert, R.; Dasser, M. J. Org. Chem. 2000, 65, 4529–4531; (m)
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1048–1058.
170.2,116.8, 72.1, 71.6, 69.0, 64.8, 34.2, 31.4, 24.7, 22.4,14.0; HRMS (CI,
isobutane) m/z 273.1334 [calcd for C13H21O6 (MþH) 273.1338].
4.5.2.3.2. (L)-Syributin 1 [(L)-10]. Yield: 42 mg, 58%. Ana-
20
lytical sample (yellowish oil): [
a
]
ꢀ6.44 (c 0.87, CHCl3); FTIR (thin
D
film/NaCl) 3400 (br m), 2957 (m), 2930 (m), 2871 (m), 1781 (m),
1738 (s), 1729 (s), 1639 (w), 1172 (m) cmꢀ1 1H NMR (500 MHz,
CDCl3)
;
d
6.05 (s, 1H), 4.97 (d, J¼18.5 Hz, 1H), 4.91 (d, J¼17.8 Hz, 1H),
4.63 (br s, 1H), 4.27 (dd, J¼12.0, 5.2 Hz, 1H), 4.17 (dd, J¼11.9, 6.7 Hz,
1H), 3.96 (br s, 1H), 3.74 (br s, 1H), 3.52 (br s, 1H), 2.34 (t, J¼7.6 Hz,
2H), 1.61 (quint., J¼7.4 Hz, 2H), 1.33–1.24 (m, 4H), 0.88 (t, J¼6.8 Hz,
3H); 13C NMR (125 MHz, CDCl3)
d 174.7,174.3,170.6, 116.7, 72.2, 71.5,
69.0, 64.8, 34.2, 31.4, 24.7, 22.4, 14.1; HRMS (CI, isobutane) m/z
273.1340 [calcd for C13H21O6 (MþH) 273.1338].
4.5.2.3.3. (D)-Syributin 2 [(D)-11]. Yield: 74 mg, 69%. Ana-
20
lytical sample (yellowish oil): [
a
]
D
þ7.05 (c 0.78, CHCl3); FTIR (thin
film/NaCl) 3388 (br m), 2954 (m), 2926 (m), 2855 (m), 1780 (m),
1740 (s), 1731 (s), 1721 (s), 1639 (m) cmꢀ1 1H NMR (500 MHz,
CDCl3)
;
d
6.08 (s, 1H), 4.97 (dd, J¼18.0, 1.7 Hz, 1H), 4.91 (d, J¼17.4 Hz,
1H), 4.61 (d, J¼3.0 Hz, 1H), 4.35 (dd, J¼11.7, 4.9 Hz, 1H), 4.18 (dd,
J¼11.8, 6.4 Hz, 1H), 3.95 (ddd, J¼6.3, 5.1, 3.3 Hz, 1H), 2.37 (t,
J¼7.4 Hz, 2H),1.66–1.60 (m, 2H),1.30–1.27 (m, 8H), 0.88 (t, J¼6.9 Hz,
3H); 13C NMR (125 MHz, CDCl3)
d 174.7, 174.5, 170.9, 116.6, 72.3,
71.5, 69.0, 64.7, 34.3, 31.8, 29.2, 29.0, 25.0, 22.7, 14.2; HRMS (CI,
isobutane) m/z 301.1651 [calcd for C15H25O6 (MþH) 301.1651].
4.5.2.3.4. (L)-Syributin 2 [(L)-11]. Yield: 17.4 mg, 65%. Ana-
20
lytical sample (colorless oil): [
a
]
D
ꢀ6.75 (c 0.59, CHCl3); FTIR (thin
film/NaCl) 3388 (s), 2957 (m), 2931 (m), 2856 (w), 1779 (m), 1737
(s), 1713 (s), 1639 (s) cmꢀ1; 1H NMR (500 MHz, CDCl3)
d
6.08 (s, 1H),
4.97 (d, J¼17.9 Hz, 1H), 4.91 (d, J¼17.4 Hz, 1H), 4.62 (s, 1H), 4.35 (dd,
J¼11.8, 4.6 Hz, 1H), 4.17 (dd, J¼11.8, 6.4 Hz, 1H), 3.96–3.94 (m, 2H),
2.37 (t, J¼7.6 Hz, 2H), 1.66–1.60 (m, 2H), 1.30–1.27 (m, 8H), 0.88 (t,
11. (a) Yoda, H.; Kawauchi, M.; Takabe, K.; Hosoya, K. Heterocycles 1997, 45, 1895–
1898; (b) Di Florio, R.; Rizzacasa, M. A. Aust. J. Chem. 2000, 53, 327–331.
12. (a) Yu, P.; Yang, Y.; Zhang, Z. Y.; Mak, T. C. W.; Wong, H. N. C. J. Org. Chem. 1997,
62, 6359–6366; (b) Yoda, H.; Kawauchi, M.; Takabe, K.; Hosoya, K. Heterocycles
1997, 45, 1903–1906; (c) Krishna, P. R.; Narsingam, M.; Kannan, V. Tetrahedron
Lett. 2004, 45, 4773–4775.
J¼6.2 Hz, 3H); 13C NMR (125 MHz, CDCl3)
d 174.7, 174.4, 170.7, 116.6,
72.2, 71.5, 69.0, 64.7, 34.3, 31.8, 29.2, 29.0, 25.0, 22.7, 14.2; HRMS (CI,
13. Carda, M.; Castillo, E.; Rodrı´guez, S.; Falomir, E.; Marco, J. A. Tetrahedron Lett.
isobutane) m/z 301.1646 [calcd for C15H25O6 (MþH) 301.1651].
1998, 39, 8895–8896.
4.5.2.3.5. (L)-Syributin 3 [(L)-12]. Yield: 15.9 mg. 58%. Ana-
14. Doyle, M. P.; Dyatkin, A. B. J. Org. Chem. 1995, 60, 3035–3038.
15. Both enantiomeric forms have been readily monosilylated. For an example
using (þ)-15 see: Taunton, J.; Collins, J. L.; Schreiber, S. L. J. Am. Chem. Soc. 1996,
118, 10412–10422.
20
lytical sample (yellowish oil): [
a]
ꢀ6.33 (c 0.68, CHCl3); FTIR (thin
D
film/NaCl) 3400 (br m), 2965 (w), 2934 (w), 2876 (w), 1780 (w),
1737 (s), 1730 (s), 1640 (w), 1178 (m) cmꢀ1 1H NMR (500 MHz,
CDCl3)
;
16. (a) Carlsen, P. H. J.; Katsuki, T.; Martin, V. S.; Sharpless, K. B. J. Org. Chem. 1981,
46, 3936–3938; (b) Calculations based on n¼1 [RuCl3(H2O)n)].
d
6.08 (q, J¼1.5 Hz, 1H), 4.97 (dd, J¼17.8, 1.7 Hz, 1H), 4.91
17. (a) Birch, P. L.; El-Obeid, H. A.; Akhtar, M. Arch. Biochem. Biophys. 1972, 148, 447–
451; (b) Coggins, J. R.; Kray, W.; Shaw, E. Biochem. J. 1974, 137, 579–585.
18. For acylation (macrolactonization) of alkyl halides using cesium carboxylates in
DMF see: (a) Kruizinga, W. H.; Kellogg, R. M. J. Chem. Soc., Chem. Commun. 1979,
286–288; (b) Kruizinga, W. H.; Kellogg, R. M. J. Am. Chem. Soc.1981,103, 5183–5189.
19. (a) Dekhane, M.; Douglas, K. T.; Gilbert, P. Tetrahedron Lett. 1996, 37, 1883–1884;
(b) The corresponding ethyl ester of 18 is commercially available.
(ddd, J¼17.6, 2.1, 1.1 Hz, 1H), 4.62 (d, J¼2.8 Hz, 1H), 4.35 (dd, J¼11.8,
5.4 Hz,1H), 4.18 (dd, J¼11.8, 6.4 Hz,1H), 3.95 (ddd, J¼7.4, 6.3, 3.3 Hz,
1H), 2.36 (t, J¼7.4 Hz, 2H), 1.67 (sext., J¼7.5 Hz, 2H), 0.97 (t,
J¼7.3 Hz, 3H); 13C NMR (125 MHz, CDCl3)
d 174.5, 174.3, 170.5, 116.7,
72.2, 71.5, 69.0, 64.8, 36.1, 18.5, 13.8; HRMS (CI, isobutane) m/z
245.1025 [calcd for C11H17O6 (MþH) 245.1025].
20. For butenolide formation employing
a dihydroxyacetone derivative see:
Sakuda, S.; Tanaka, S.; Mizuno, K.; Sukcharoen, O.; Nihira, T.; Yamada, Y. J. Chem.
Soc., Perkin Trans. 1 1993, 2309–2315.
21. The atomic coordinates for structure 3 have been deposited with the Cam-
bridge Crystallographic Data Centre: Navarro Villalobos, Mauricio. Thesis1 de-
position to the Cambridge Structural Database, deposition number CCDC
150205.
Acknowledgements
This work was supported by Yale University and was performed
in the W6 laboratories of Professor John L. Wood under his lead-
ership. The Camille and Henry Dreyfus Foundation (NF-93-0) and
the American Cancer Society (JFRA-523) provided additional sup-
port through their Junior Faculty Award programs.
22. The two-step intramolecular Wittig olefination was performed following the
method by Yamada: Niwa, H.; Okamoto, O.; Miyachi, Y.; Uosaki, Y.; Yamada, K.
J. Org. Chem. 1987, 52, 2941–2943.
23. Alcohol 25 and esters (þ)-26a–b were previously prepared by Mukai5 using
this method.
24. Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923–2925.
25. Gottlieb, H. E.; Kotlyar, V.; Nudelman, A. J. Org. Chem. 1997, 62, 7512–7515.
26. For safety working with diazomethane see: (a) Moore, J. A.; Reed, D. E. Org. Synth.
1961, 41, 16–20; (b) Moore, J. A.; Reed, D. E. Org. Synth. 1973, Collect 5, 351–355.
27. We prepared the ethereous diazomethane solution using a DiazaldÒ kit with
Clear-sealÒ joints. For additional safety and preparation see: Black, T. H.
Aldrichimica Acta 1983, 16, 3–10.
References and notes
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