Biosynthesis of the Hypocholesterolemic Agent Mevinolin by Aspergillus terreus. Determination of the Origin of Carbon, Hydrogen, and Oxygen Atoms by 13C NMR and Mass Spectrometry

Journal of the American Chemical Society

Volumn 107, Issue 12, 1985, Pages 3694-3701

  Moore, Richard N ^a   Bigam, Glen ^a   Chan, Jean K ^a   Hogg, Alan M ^a   Nakashima, Thomas T ^a   Vederas, John C ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

MEVINOLIN; RADIOISOTOPE;

ACETIC ACID C 13; ACETIC ACID C 13 H 2; ACETIC ACID C 13 O 18; DRUG ANALYSIS; DRUG IDENTIFICATION; DRUG METABOLISM; DRUG STRUCTURE; FUNGUS; IN VITRO STUDY; MASS SPECTROMETRY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; PRIORITY JOURNAL;

EID: 0021962589     PISSN: 00027863     EISSN: 15205126     Source Type: Journal    
DOI: 10.1021/ja00298a046     Document Type: Article

References (53)

1. Mevinolin (1) from Aspergillus terreus and monacolin K from Monascus ruber (Endo, A. J. Antibiot. 1979, 32, 852–854. Endo, A. J. Antibiot. 1980, 33, 334–336) appear to be the same compound; compactin (2) is also known as ML-236B.
2. Alberts, A. W.; Chen, J.; Kuron, G.; Hunt, V.; Huff, J.; Hoffman, C.; Rothrock, J.; Lopez, M.; Joshua, H.; Harris, E.; Patchett, A.; Monaghan, R.; Currie, S.; Stapley, E.; Albers-Schonberg, G.; Hensens, O.; Hirshfield, J.; Hoogsteen, K.; Liesch, J.; Springer, J. Proc. Natl. Acad. Sci. U.S.A. 1980, 77, 3957–3961. (b) Brown, A. G.; Smale, T. C.; King, T. J.; Hasenkamp, R.; Thompson, R. H. J. Chem. Soc., Perkin Trans. 1 1976, 1165–1170. (c) Endo, A.; Kuroda, M.; Tsujita, Y. J. Antibiot. 1976, 29, 1346–1348.
3. Fears, R. Biochem. Soc. Trans. 1983, 11, 642–644. (b) Tobert, J. A.; Hitzenberger, G.; Kukovetz, W. R.; Holmes, I. B.; Jones, K. H. Atherosclerosis 1982, 41, 61–65. (c) Kroon, P. A.; Hand, K. M.; Huff, J. W.; Alberts, A. W. Biochem. Soc. Trans. 1982, 44, 41–48. (d) Tobert, J. A.; Bell, G. D.; Birtwell, J.; Kukovetz, W. R.; Pryor, J. S.; Buntinx, A.; Holmes, I. B.; Chao, Y. S.; Bolognese, J. A. J. Clin. Invest. 1982, 69, 913–919. (e) Kritchevsky, D.; Tepper, S. A.; Klurfeld, D. M. Pharmacol. Res. Commun. 1981, 13, 921–926.
4. Albers-Schönberg, G.; Joshua, H.; Lopez, M. B.; Hensens, O. D.; Springer, J. P.; Chen, J.; Ostrove, S.; Hoffman, C. H.; Alberts, A. W.; Patchett, A. A. J. Antibiot. 1981, 34, 507–512. (b) Lam, Y. K. T.; Gullo, V. P.; Goegelman, R. T.; Jorn, D.; Huang, L.; DeRiso, C.; Monaghan, R. L.; Putter, I. J. Antibiot. 1981, 34, 614–616.
5. Endo, A. Trends Biochem. Sci. 1981, 6, 10–13. (b) Endo, A. Methods Enzymol. 1981, 72D, 684–689. (c) Bach, T. J.; Lichtenthaler, H. K. Z. Naturforsch., C 1983, 38C, 212–219.
6. Krieger, M. Anal. Biochem. 1983, 135, 383–391.
7. Ranganathan, S.; Nambudiri, A. M. D.; Rudney, H. Arch. Biochem. Biophys. 1981, 210, 592–597.
8. Carson, D. D.; Lennarz, W. J. J. Biol. Chem. 1981, 256, 4679–4686.
9. Hiruma, K.; Yagi, S.; Endo, A. Appl. Entomol. Zool. 1983, 18, 111–115. (b) Edwards, J. P.; Price, N. R. Insect Biochem. 1983, 13, 185–189. (c) Monger, D. J.; Lim, W. A.; Kezdy, F. J.; Law, J. H. Biochem. Biophys. Res. Commun. 1982, 105, 1374–1380.
10. Bach, T. J.; Lichtenthaler, H. K. Physiol. Plant. 1983, 59, 50–60.
11. Shiao, M. S. Bot. Bull. Acad. Sin. 1983, 24, 135–143.
12. Sato, Y.; Masuda, A.; Ono, M.; Kuwano, M. Biochem. Biophys. Res. Commun. 1983, 117, 13–21. (b) Chao, Y. S.; Kroon, P. A.; Yamin, T. T.; Thompson, G. M.; Alberts, A. W. Biochim. Biophys. Acta 1983, 754, 134–141. (c) Maxwell, R. E.; Nawrocki, J. W.; Ualendorf, P. D. Atherosclerosis 1983, 48, 195–203. (d) Edwards, P. A.; Lan, S. F.; Fogelman, A. M. J. Biol. Chem. 1983, 258, 10219–10222. (e) Astruc, M.; Roussillon, S.; DeFay, R.; Descomps, B.; Crastes de Paulet, A. Biochim, Biophys. Acta 1983, 763, 11–18. (f) Clarke, C. F.; Edwards, P. A.; Lan, S. F.; Tanaka, R. D.; Fogelman, A. M. Proc. Natl. Acad. Sci. U.S.A. 1983, 80, 3305–3308. (g) Brown, K.; Havel, C. M.; Watson, J. A. J. Biol. Chem. 1983, 258, 8512–8518. (h) Hashizume, T.; Matsubara, S.; Endo, A. Agric. Biol. Chem. 1983, 47, 1401–1403. (i) Davis, R. A.; Highsmith, W. E.; McNeal, M. M.; Schexnayder, J. A.; Kuan, J. C. W. J. Biol. Chem. 1983, 258, 4079–4082. (j) Hardeman, E. C.; Jenke, H. S.; Simoni, R. D. Proc. Natl. Acad. Sci. U.S.A. 1983, 80, 1516–1520. (k) Kopito, R. R.; Murray, D. M.; Story, D. L.; Brunengraber, H. J. Biol. Chem. 1984, 259, 372–377.
13. Mevinolin synthesis: (a) Hirama, M.; Iwashita, M. Tetrahedron Lett. 1983, 24, 1811–1812. Compactin syntheses; (b) Hsu, C. T.; Wang, N. Y.; Latimer, L. H.; Sih, C. J. J. Am. Chem. Soc. 1983, 105, 593–601. (c) Hirama, M.; Uei, M. Tetrahedron Lett. 1982, 104, 4251–4253. (d) Girotra, N. N.; Wendler, N. L. Tetrahedron Lett. 1982, 23, 5501–5504. (e) Grieco, P. A.; Zelle, R. E.; Lis, R.; Finn, J. J. Am. Chem. Soc. 1983, 105, 1403–1404. Dihydrocompactin synthesis: (f) Yang, Y. L.; Manna, S.; Falck, J. R. J. Am. Chem. Soc. 1984, 106, 3811–3814. Dihydromevinolin Synthesis: (g) Falck, J. R.; Yang, Y. L. Tetrahedron Lett. 1984, 25, 3563–3566.
14. Lactone portion: (a) Danishefsky, S.; Kerwin, J. F., Jr.; Kobayashi, S. J. Am. Chem. Soc. 1982, 104, 358–360. (b) Prugh, J. D.; Deana, A. A. Tetrahedron Lett. 1982, 23, 281–284. (c) Yang, Y. L.; Falck, J. R. Tetrahedron Lett. 1982, 23, 4305–4308. (d) Ho, P. T.; Chung, S. Carbohydr. Res. 1984, 125, 318–322. (e) Majewski, M.; Clive, D. L. J.; Anderson, P. C. Tetrahedron Lett. 1984, 25, 2101–2104.
15. Hexahydronaphthalene portion: (a) Funk, R. L.; Zeller, W. E. J. Org. Chem. 1982, 47, 180–182. (b) Deutsch, E. A.; Snider, B. B. J. Org. Chem. 1982, 47, 2682–2684. (c) Heathcock, C. H.; Taschner, M. J.; Rosen, T.; Thomas, J. A.; Hadley, C. R.; Popjak, G. Tetrahedron Lett. 1982, 23, 4747–4750. (d) Anderson, P. C.; Clive, D. L. J.; Evans, C. J. Org. Chem. 1983, 24, 1373–1376. (e) Girotra, N. N.; Wendler, N. L. Tetrahedron Lett. 1983, 24, 3687–3688. (f) Deutsch, E. A.; Snider, B. B. J. Org. Chem. 1983, 24, 3701–3704. (g) Funk, R. L.; Mossman, C. J.; Zeller, W. E. J. Org. Chem. 1984, 25, 1655–1658. (h) Girotra, N. N.; Reamer, R. A.; Wendler, N. L. J. Org. Chem. 1984, 25, 5371–5372.
16. Lee, T. J.; Holtz, W. J.; Smith, R. L. J. Org. Chem. 1982, 47, 4750–4757. (b) Willard, A. K.; Smith, R. L. J. Labelled Compd. Radiopharm. 1982, 19, 337–344. (c) Kuo, C. H.; Patchett, A. A.; Wendler, N. L. J. Org. Chem. 1983, 48, 1991–1998.
17. Okazaki, T.; Serizawa, N.; Enokita, R. J. Antibiot. 1983, 36, 1176–1183 and references therein. (b) Serizawa, N.; Nakagawa, K.; Tsujita, Y.; Terahara, A.; Kuwano, H. J. Antibiot. 1983, 36, 608–610.
18. Turner, W. B.; Aldridge, D. C. “Fungal Metabolites II”; Academic Press: New York, 1983; pp 138–139, 180.
19. Steyn, P. S.; Wessels, P. L.; Holzapfel, C. W.; Potgieter, D. J. J.; Louw, W. K. A. Tetrahedron 1972, 28, 4775–4785.
20. McGahren, W. J.; Ellestad, G. A.; Lancaster, J. E.; Morton, G. O.; Kunstmann, M. P. J. Am. Chem. Soc. 1974, 96, 1616–1617. (b) Fukuyama, K.; Tsukihara, T.; Katsube, Y.; Hamasaki, T.; Hatsuda, Y. Tetrahedron Lett. 1976, 189–190.
21. Chan, J. K.; Moore, R. N.; Nakashima, T. T.; Vederas, J. C. J. Am. Chem. Soc. 1983, 105, 3334–3336.
22. Perrin, D. D.; Armarego, W. L. F.; Perrin, D. R. “Purification of Laboratory Chemicals”, 2nd Ed.; Pergamon Press: New York, 1982.
23. Jones, L. H.; McLaren, E. J. Chem. Phys. 1954, 22, 1796–1800.
24. Moses, C. G.; Reid, E. E. J. Am. Chem. Soc. 1932, 54, 2101–2103. (b) Risley, J. M.; Van Etten, R. L. J. Am. Chem. Soc. 1980, 102, 4609–4614.
25. Rabenstein, D. L.; Nakashima, T. T. Anal. Chem. 1979, 51, 1465A-I474A and references therein. (b) Brown, D. W.; Nakashima, T. T.; Rabenstein, D. L. J. Magn. Reson. 1981, 45, 302–314. (c) Bendall, M. R.; Pegg, D. T.; Doddrell, D. M.; John, S. R.; Willing, R. I. J. Chem. Soc., Chem. Commun. 1982, 1138–1140.
26. Bax, A.; Freeman, R.; Frenkiel, T. A. J. Am. Chem. Soc. 1981, 103, 2102–2104. (b) Neszmelyi, A.; Hull, W. E.; Lukacs, G. Tetrahedron Lett. 1982, 23, 5071–5074.
27. Nakashima, T. T.; John, B. K.; McClung, R. E. D. J. Magn. Reson. 1984, 59, 124–131. (b) Nakashima, T. T.; John, B. K.; McClung, R. E. D. J. Magn. Reson. 1984, 57, 149–151.
28. Garson, M. J.; Staunton, J. Chem. Soc. Rev. 1979, 539–561. (b) Wehrli, F. W.; Nishida, T. Prog. Chem. Org. Nat. Prod. 1979, 36, 1–229. (c) Simpson, T. J. In “Biosynthesis”; Royal Society of Chemistry: London, 1984; Vol. 7, pp 1–44.
29. For a review of modern NMR pulse methods see: Benn, R.; Günther, H. Angew. Chem., Int. Ed. Engl. 1983, 22, 350–380. For a review of carbon-proton connectivity determination by NMR see: Kessler, H.; Bernd, M.; Kogler, H.; Zarbock, J.; Sorensen, O. W.; Bodenhausen, G.; Ernst, R. R. J. Am. Chem. Soc. 1983, 105, 6944–6952.
30. Doddrell, D. M.; Pegg, D. T.; Bendall, M. R. J. Magn. Reson. 1982, 48, 323–327.
31. Levitt, M. H.; Sorensen, O. W.; Ernst, R. R. Chem. Phys. Lett. 1983, 94, 540–542. (b) Bendall, M. R.; Pegg, D. T. J. Magn. Reson. 1983, 55, 114–127.
32. Bax, A.; Freeman, R.; Kempsell, S. P. J. Am. Chem. Soc. 1980, 102, 4849–4851. (b) Neszmelyi, A.; Lukacs, G. J. Chem. Soc., Chem. Commun. 1981, 999–1001. (c) Bax, A.; Freeman, R.; Frenkiel, T. A.; Levitt, M. H. J. Magn. Reson. 1981, 43, 478–483. (d) Turner, D. L. J. Magn. Reson. 1982, 49, 175–178. (e) Robinson, J. A.; Turner, D. L. J. Chem. Soc., Chem. Commun. 1982, 148–151. (f) Ashworth, D. M.; Robinson, J. A.; Turner, D. L. J. Magn. Reson. 1982, 491–493. (g) Freeman, R.; Frenkiel, T.; Rubin, M. B. J. Am. Chem. Soc. 1982, 104, 5545–5547. (h) Pinto, A. C.; DoPrado, S. K.; Filho, R. B.; Hull, W. E.; Neszmelyi, A.; Lukacs, G. Tetrahedron Lett. 1982, 23, 5267–5270. (i) Schmitz, F. J.; Agarwal, S. K.; Gunasekara, S. P.; Schmidt, P. G.; Shoolery, J. N. J. Am. Chem. Soc. 1983, 105, 4835–4836. (j) Garcia Alvarez, M. C.; Lukacs, G.; Neszmelyi, A.; Piozzi, F.; Rodriguez, B.; Savona, G. J. Org. Chem. 1983, 48, 5123–5126.
33. 6] glucose: (a) Gould, S. J.; Cane, D. E. J. Am. Chem. Soc. 1982, 104, 343–346. (b) Rinehart, K. L.; Jr.; Potgieter, M.; Wright, D. A. J. Magn. Reson. 1982, 104, 2649–2652.
34. Bacher, A.; Le Van, Q.; Bühler, M.; Keller, P. J.; Eimicke, V.; Floss, H. G. J. Am. Chem. Soc. 1982, 104, 3754–3755. (b) Mackenzie, N.; Baxter, R. L.; Scott, A. I.; Fagerness, P. E. J. Chem. Soc., Chem. Commun. 1982, 145–147.
35. Keller, P. J.; Le Van, Q.; Bacher, A.; Floss, H. G. Tetrahedron 1983, 21, 3471–3481. (b) Seo, S.; Uomori, A.; Yoshimura, Y.; Takeda, K. J. Am. Chem. Soc. 1983, 105, 6343–6344. (c) Ubukata, M.; Uzawa, J.; Isono, K. Tetrahedron 1984, 106, 2213–2214.
36. Metzler, D. E. “Biochemistry, The Chemical Reactions of Living Cells”; Academic Press: New York, 1977; pp 832–835.
37. Snyder, W. C.; Rinehart, K. L., Jr. J. Am. Chem. Soc. 1984, 106, 787–789 and references therein.
38. For reviews see: (a) Turner, W. B. “Fungal Metabolites”; Academic Press: New York, 1971; Vol. 1, pp 62–84. (b) Weiss, U.; Edwards, J. M. “Biosynthesis of Aromatic Compounds”; Wiley: New York, 1980; pp 326–502. (c) Manitto, P. “Biosynthesis of Natural Products”; Wiley: New York, 1981; pp 169–212. (d) Herbert, R. B. “The Biosynthesis of Secondary Metabolites”; Chapman and Hall: London, 1981; pp 28–49.
39. Vederas, J. C.; Graf, W.; David, L.; Tamm, C. Helv. Chim. Acta 1975, 58, 1886–1898.
40. Townsend, C. A.; Christensen, S. B. Tetrahedron 1983, 39, 3575–3582. (b) Townsend, C. A.; Christensen, S.; Trautwein, T. J. Am. Chem. Soc. 1984, 106, 3868–3869.
41. Lane, M. P.; Nakashima, T. T.; Vederas, J. C. J. Am. Chem. Soc. 1982, 104, 913–915. (b) Hill, J. G.; Nakashima, T. T.; Vederas, J. C. Tetrahedron 1982, 104, 1745–1748.
42. Cane, D. E.; Celmer, W. D.; Westley, J. W. J. Am. Chem. Soc. 1983, 105, 3594–3600. (b) Hutchinson, C. R. Acc. Chem. Res. 1983, 16, 7–14.
43. Cane, D. E.; Hasler, H.; Taylor, P. B.; Liang, T. C. Tetrahedron 1983, 39, 3449–3545. (b) Hutchinson, C. R.; Shu-Wen, L.; McInnes, A. G.; Walter, J. A. Tetrahedron 1983, 39, 3507–3513. (c) Jones, R. C. F. Nat. Prod. Rep. 1984, 1, 87–103.
44. 21 as well as: (a) Vederas, J. C. Can. J. Chem. 1982, 60, 1637–1642. (b) Ajaz, A. A.; Robinson, J. A. J. Chem. Soc., Chem. Commun. 1983, 679–680. (c) Colombo, L.; Scolastico, C.; Lukacs, G.; Dessinges, A.; Aragozzini, F.; Merendi, C. Tetrahedron 1983, 1436–1437. (d) Cane, D. E.; Liang, T. C.; Kaplan, L.; Nallin, M. K.; Schulman, M. D.; Hensens, O. D.; Douglas, A. W.; Albers-Schonberg, G. J. Am. Chem. Soc. 1983, 105, 4110–4112. (e) King, J. F.; Skonieczny, S.; Khemani, K. C.; Stothers, J. B. Tetrahedron 1983, 105, 6514–6515. (f) Sankawa, U.; Ebizuka, Y.; Noguchi, H.; Isikawa, Y.; Kitaghawa, S.; Yamamoto, Y.; Kobayashi, T.; Iitak, Y. Tetrahedron 1983, 39, 3583-3591. (g) Dessinges, A.; Castillon, S.; Olesker, A.; Thang, T. T.; Lukacs, G. J. Am. Chem. Soc. 1984, 106, 450–451. (h) Cane, D. E.; Yang, C. C. Tetrahedron 1984, 106, 784–787. (i) Wood, T. G.; Weisz, O. A.; Kozarich, J. W. Tetrahedron 1984, 106, 2222–2223. (j) Holtum, J. A. M.; Summons, R.; Roeske, C. A.; Comins, H. N.; O'Leary, M. H. J. Biol. Chem. 1984, 259, 6870–6881. (k) Scott, F. E.; Simpson, T. J.; Trimble, L. A.; Vederas, J. C. J. Chem. Soc., Chem. Commun. 1984, 756–758. (1) McIntyre, C. R.; Simpson, T. J.; Trimble, L. A.; Vederas, J. C. Tetrahedron 1984, 706–709.
45. Compartmentalization is known to occur in mammalian β-oxidation of fatty acids: Bremer, J.; Osmundsen, H. In “Fatty Acid Metabolism and its Regulation”; Numa, S., Ed.; Elsevier: New York, 1984; pp 113–154. See also: Kindl, H., Tetrahedron pp 187–191.
46. McInnes, A. G.; Walter, J. A.; Wright, J. L. C. Tetrahedron 1983, 39, 3515–3522 and references therein. (b) Anderson, V. E.; Hammes, G. G. Biochemistry 1984, 23, 2088–2094.
47. Schmitt, P.; Wesener, J. R.; Gunther, H. J. Magn. Reson. 1983, 52, 511–514. (b) Doddrell, D. M.; Staunton, J.; Laue, E. J. Magn. Reson. 1983, 52, 523–528. (c) Doddrell, D. M.; Staunton, J.; Laue, E. D. J. Chem. Soc., Chem. Commun. 1983, 602–605. (d) Abell, C.; Doddrell, D. M.; Garson, M. J.; Laue, E. D.; Staunton, J. J. Magn. Reson. 1983, 694–696. (e) Rinaldi, P. L.; Baldwin, N. J. J. Am. Chem. Soc. 1983, 105, 7523–7527. (f) Crout, D. H. G.; Lutstorf, M.; Morgan, P. J. Tetrahedron 1983, 39, 3457–3469. (g) Wesener, J.; Schmitt, P.; Günther, H. J. Am. Chem. Soc. 1984, 106, 10–13. (h) Golebiewski, W. M.; Spenser, I. D. J. Magn. Reson. 1984, 106, 1441–1442.
48. Staunton, J.; Abell, C. J. Am. Chem. Soc., Chem. Commun. 1981, 856–858. (b) Simpson, T. J.; De Jesus, A. E.; Steyn, P. S.; Vleggaar, R. J. Magn. Reson. 1982, 632-634. (c) Stoessl, A.; Stothers, J. B. J. Magn. Reson. 1982, 880–881. (d) Simpson, T. J.; Stenzel, D. J. J. Magn. Reson. 1982, 890–892. (e) Leeper, F. J.; Staunton, J. J. Magn. Reson. 1982, 911–912. (f) Simpson, T. J.; Stenzel, D. J. J. Magn. Reson. 1982, 1074–1016. (g) Jurlina, J. L.; Stothers, J. B. J. Am. Chem. Soc. 1982, 104, 4677–4678.
49. Alberts, A. W.; Greenspan, M. D. In “Fatty Acid Metabolism and its Regulation”; Numa, S., Ed,; Elsevier: New York, 1984; pp 29–58.
50. Shapiro, S.; Piper, J. U.; Caspi, E. J. Am. Chem. Soc. 1982, 104, 2301–2305 and references therein. (b) Caspi, E.; Arunachalam, T.; Nelson, P. A. J. Am. Chem. Soc. 1983, 105, 6987–6989.
51. Tamm, C.H. In “The Biosynthesis of Mycotoxins”; Steyn, P. S., Ed.; Academic Press, 1980; pp 269–299.
52. Banfield, J. E.; Black, D. S. C.; Johns, S. R.; Willing, R. I. Aust. J. Chem. 1982, 35, 2247–2256 and references therein. (b) Nicolaou, K. C.; Zipkin, R. E.; Petasis, N. A. J. Am. Chem. Soc. 1982, 104, 5558–5560.
53. 39 ilicicolin H (Tanabe, M.; Urano, S. Tetrahedron 1983, 39, 3569-3574); chlorothricin (Mascaretti, O. A.; Chang, C.; Hook, D.; Otsuka, H.; Kreutzer, E. F.; Floss, H. G. Biochemistry 1981, 20, 919-924); and tetrocarcin (Tamaoki, T.; Tomita, F. J. Antibiot. 1983, 36, 595–598).