Total synthesis of (+)-conagenin

Tetrahedron Letters

Volumn 37, Issue 23, 1996, Pages 4047-4050

  Hatakeyama, Susumi ^a   Fukuyama, Hiroko ^a   Mukugi, Yasuko ^a   Irie, Hiroshi ^a  

^a NAGASAKI UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

CONAGENIN; IMMUNOMODULATING AGENT; UNCLASSIFIED DRUG;

ARTICLE; CHIRALITY; DRUG SYNTHESIS; STEREOCHEMISTRY;

STREPTOMYCES ROSEOSPORUS;

EID: 0030003944     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)00758-7     Document Type: Article

References (30)

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2. (a) Kawatsu, M.; Yamashita, T.; Osono, M.; Ishizuka, M.; Takeuchi, T. J. Antibiot. 1993, 46, 1687-1691.
3. (b) Kawatsu, M.; Yamashita, T.; Osono, M.; Masuda, T.; Ishizuka, M.; Takeuchi, T. J. Antibiot. 1993, 46, 1692-1698.
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5. Kawatsu, M.; Yamashita, T.; Ishizuka, M.; Takeuchi, T. J. Antibiot. 1995, 48, 222-225.
6. Recently, the synthesis of two diastereoisomers of conagenin was reported, see: Kovács-Kulyassa, Å.; Herczegh, P.; Sztaricskai, F. J. Tetrahedron Lett. 1996, 37, 2499-2502.
7. For reviews, see: (a) Heathcock, C. H. Comprehensive Organic Synthesis, Trost, B. M., Fleming, I., Heathcock, C. H., Eds.; Pergamon Press: Oxford, 1991; Vol. 2, pp 181-238.
8. (b) Kim, M.; Williams, S. F.; Masamune, S. Comprehensive Organic Synthesis, Trost, B. M., Fleming, I., Heathcock, C. H., Eds.; Pergamon Press: Oxford, 1991; Vol. 2, pp 239-275.
9. For a review, see: Nicholas, G. Comprehensive Organic Synthesis, Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 8, pp 1-24.
10. Paterson, I.; Goodman, J. M.; Lister, M. A.; Schumann, R. C.; McClure, C. K.; Norcross, R. D. Tetrahedron 1990, 46, 4663-4684.
11. 4 reduction was conducted without addition of MeOH.
12. For related one-pot aldol-reduction procedures, see: Bonini, C.; Racioppi, R.; Righi, G.; Rossi, L. Tetrahedron: Asymmetry 1994, 5, 173-176.
13. 13C resonances of the acetonide carbons to the empirical rule: Cf.: Rychnovsky, S. D.; Skalitzky, D. J. Tetrahedron Lett. 1990, 31, 945-948; Evans, D. A.; Rieger, D. L.; Gage, J. R. Tetrahedron Lett. 1990, 31, 7099-7100.
14. 13C resonances of the acetonide carbons to the empirical rule: Cf.: Rychnovsky, S. D.; Skalitzky, D. J. Tetrahedron Lett. 1990, 31, 945-948; Evans, D. A.; Rieger, D. L.; Gage, J. R. Tetrahedron Lett. 1990, 31, 7099-7100.
15. These results suggests that the reduction of 2 occurred with syn-selectivity of ca 89% de whereas the chelated enantiomeric aldol was reduced with complete syn-selectivity giving only the enantiomer of 3.
16. Kusumi, T. J. Synth. Org. Chem. Jpn. 1993, 50, 462-470.
17. Prepared by monoacetylation, chromatographic separation, and esterification using (R)-or (S)-α.-methoxy-α-trifluoromethylphenylacetyl chloride.
18. Carlsen, P. H. J.; Katsuki, T.; Martin, V. S.; Sharpless, K. B. J. Org. Chem. 1981, 46, 3936-3938.
19. α-Substituted-α-amino acids such as a-methylserine have received a great deal of recent attention, see: (a) Moon, S.-H.; Ohfune, Y. J. Am. Chem. Soc. 1994, 116, 7405-7406.
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26. 1H NMR analysis of the corresponding (R)- and (S)-MTPA esters.
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29. Both natural and synthetic specimens were purified by HPLC (ODS column, 5% aq. MeCN) under the same conditions before spectroscopic comparisons.
30. 3) data are following. 5: δ 8.23 (br, 1H), 5.14 (d, 1H, J = 3.7 Hz), 4.96 (quint, 1H, J = 6.4 Hz), 2.29 (J = 3.7, 6.4, 7.1 Hz, 1H,), 2.15 (s, 3H), 2.04 (s, 3H), 1.24 (d, 3H, J = 6.4 Hz), 1.08 (d, 3H, J = 7.0 Hz); δ 174.1, 170.9, 170.5, 72.5, 71.3, 39.4, 21.0, 20.5, 17.3, 10.4. 12: δ 7.35 (m, 5H), 5.28 (s, 1H), 5.23 (d, 1H, J = 12.2 Hz), 5.18 (d, 1H, J = 12.2 Hz), 4.00 (dd, 1H, J = 5.8, 11.3 Hz), 3.80 (dd, 1H, J = 7.8, 11.3 Hz), 3.20 (br s, 1H), 1.48 (s, 3H), 1.42 (s, 9H); δ 173.3, 155.4, 135.4, 128.6, 128.3, 128.1, 80.3, 67.4, 67.0, 61.0, 28.3, 20.8. 13: δ 7.35 (m, 5H), 5.24 (d, 1H, J = 12.4 Hz), 5.18 (d, 1H, J = 12.4 Hz), 5.01 (d, 1H, J = 5.3 Hz), 4.97 (dq, 1H, J = 5.0, 6.4 Hz), 4.14 (br d, 1H, J = 11.3 Hz), 3.86 (br d, 1H, J = 11.3 Hz), 3.27 (br s, 1H), 2.50 (m, 1H), 2.15 (s, 3H), 2.05 (s, 3H), 1.56 (s, 3H), 1.20 (d, 3H, J = 6.4 Hz), 0.99 (d, 3H, J = 7.1 Hz); δ 172.7, 170.9, 170.4, 168.9, 135.1, 128.6, 128.4, 128.0, 75.0, 71.1, 67.7, 65.3, 62.3, 39.7, 21.2, 20.7, 19.6, 17.9, 9.6. Conagenin methyl ester: δ 7.56 (br s, 1H), 4.50 (br s, 1H), 4.32 (d, 1H, J = 2.1 Hz), 4.22 (dq, 1H, J = 2.1, 6.4 Hz), 4.07 (d, 1H, J = 11.4 Hz), 3.83 (d, 1H, J = 11.4 Hz), 3.80 (s, 3H), 2.40 (br s, 1H), 2.06 (tq, 1H, J = 2.1, 7.1 Hz), 1.82 (br s, 1H), 1.55 (s, 3H), 1.24 (d, 3H, J = 6.4 Hz), 0.92 (d, 3H, J = 7.1 Hz); δ 173.4, 173.2, 76.8, 72.0, 66.6, 62.1, 53.1, 40.6, 21.8, 20.4, 5.2.