Structures and partial stereochemical assignments for prymnesin-1 and prymnesin-2: Potent hemolytic and ichthyotoxic glycosides isolated from the red tide alga Prymnesium parvum

Journal of the American Chemical Society

Volumn 121, Issue 37, 1999, Pages 8499-8511

  Igarashi, Tomoji ^a,b   Satake, Masayuki ^a   Yasumoto, Takeshi ^a,b  

^a TOHOKU UNIVERSITY   (Japan)

^b JAPAN FOOD RESEARCH LABORATORIES   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ACETIC ACID; CHLORINE; DECALIN DERIVATIVE; ETHER DERIVATIVE; FISH VENOM; FURAN DERIVATIVE; GALACTOSE; GLYCOSIDE; NITROGEN; PYRAN DERIVATIVE; SOLVENT; XYLOSE;

ALGA; ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CHEMICAL BOND; CHIRALITY; CONFORMATION; HEMOLYSIS; NONHUMAN; STEREOCHEMISTRY; TOXIN STRUCTURE;

EID: 0033595508     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja991740e     Document Type: Article

References (50)

1. Prymnesium parvum was first described by Carter, N. Arch. Protistenk. 1937, 90, 40-43. It belongs to the haptophytes and differs markedly from the dinophytes that are often involved in seafood poisoning by producing the brevetoxins, ciguatoxins, and saxitoxins, etc.
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8. 6c (a) Paster, Z. Rev. Int. Oceanogr. Med. 1968, 10, 249-258. (b) Ulitzur, S.; Shilo, M. Biochim. Biophys. Acta 1970, 207, 350-363. (c) Parnas, I. J. Zool. 1963 12, 15-23.
9. 6c (a) Paster, Z. Rev. Int. Oceanogr. Med. 1968, 10, 249-258. (b) Ulitzur, S.; Shilo, M. Biochim. Biophys. Acta 1970, 207, 350-363. Parnas, I. J. Zool. 1963 12, 15-23.
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13. -1.
14. Murata, M.; Naoki, H.; Matsunaga, S.; Satake, M.; Yasumoto, T. J. Am. Chem. Soc. 1994, 116, 7098-7107.
15. H18-H19, 15 Hz.
16. 3COOD (19: 1), the signals in question were separated as follows: H58 (δ 4.06), H60 (δ 4.22), H57 (δ 3.32), H61(δ 3.24).
17. Carbons of NAPRM2 comprised 2 methyls, 24 methylenes, 10 olefinic methines, 54 other methines, and 8 quaternary carbons.
18. Since the sp2 carbon of C1 possesses a chlorine atom, the coupling constant of C1-H1 should be approximately 200 Hz as described in Levy, G. C.; Nelson, G. L. Carbon-13 Nuclear Magnetic Resonance for Organic Chemists; John Wiley & Sons: New York, 1972; p 69.
19. C1-H1 at 200 Hz, based on the split peak width.
20. 7
21. Georfieff, K. K.; Cave, W. T.; Blaikie, K. G. J. Am. Chem. Soc. 1954, 76, 5494-5499.
22. The chemical shifts (δ H and δ C) and coupling constants shown below were described in the literature; Hirsh, S.; Carmely, S.; Kashman, Y. Tetrahedron 1987, 43, 3257-3261. (equation presented)
23. The proton numbers in parentheses indicate the positions after the dehydrochlorination.
24. The long-range coupling constant of 1.2 Hz between H86 and H90 well matched the literature value; Joure, M. P.; Simonnin, M. P. Compt. Rend. 1963, 257, 121. If the number of triple bonds exceeded three, the coupling constant should be less than 0.6 Hz. Absence of additional quaternary carbons in the range δ 60-100 further supports the proposed terminal structure.
25. The procedure for trifluoroacetylation and GC analyses basically followed the method of Matsunaga, S.; Fusetani, N.; Kato, Y. J. Am. Chem. Soc. 1991, 113, 9690-9692.
26. H1-H2 < 0.5 Hz).
27. H1-H2 < 0.5 Hz).
28. H1-H2 < 0.5 Hz).
29. Intense cross-peaks except for vicinal and geminal correlations in the rings A-N in the NOESY of NAPRM2(occasionally of PRM2) showed close distances of H20/H24, H20/H22b, H21a/H23, H22b/H24, H23/H25a, H23/H27, H24/H26, H25a/H27, H26/H28b, H26/H30, H27/H29, H28b/H30, H29/H31a, H29/H34, H31b/H33, H32/Me91, H33/H37, H33/H35b, H34/H36a, H35/H37, H36a,b/H38, H37/H39, H38/H42, H39/Me91, H40a/Me91, H40b/H42, H41/Me91, H41/H43a, H41/H45, H42/H44b, H43a/H45, H44a/H46, H45/H47a, H46/H50, H47/H49, H49/H51b, H49/H53, H50/H52, H51b/H53, H52/H54, H52/H55a,b, H54/H58, H55b/H57, H57/H59b, H57/H61, H59b/H61, H60/H62, H61/H63a,b, H62/H64a, H62/H66, H63b/H65, H64a/H66, H65/H67, H65/H69, H67/H69, H69/H71, and H70/H74.
30. Murata, M.; Legrand, A. M.; Ishibashi, Y.; Fukui, M.; Yasumoto, T. J. Am. Chem. Soc. 1990, 112, 4381-4386.
31. Energy calculations of the rotamers and ring conformations were carried out with molecular mechanics using Allinger's parameters: (a) Werz, D. H.; Allinger, N. L. Tetrahedron 1979, 35, 3. (b) Allinger, N. L. J. Am. Chem. Soc. 1977, 99, 8127.
32. Energy calculations of the rotamers and ring conformations were carried out with molecular mechanics using Allinger's parameters: (a) Werz, D. H.; Allinger, N. L. Tetrahedron 1979, 35, 3. (b) Allinger, N. L. J. Am. Chem. Soc. 1977, 99, 8127.
33. 2O (8:2), which provided a better solubility for the peracetate.
34. 1H COSY and HOHAHA spectra of the perhydrogenated product were difficult. Therefore, we focused on the characteristic and intense cross-peaks arising from protons in the vicinity of the chlorine atoms, e.g., H54/H55, H56/H57, or H83/H84. Assignments of these signals were also supported by ID NOE experiments. Thus, two chlorine atoms, on C56 and C85, respectively, were confirmed to remain in the molecule but the chlorine atom at C1 was substituted by a hydrogen during hydrogenation.
35. 1H-1D spectra of PRM2, NAPRM2, and PAPRM2.
36. (a) Sasaki, M.; Matsumori, N.; Maruyama, T.; Nonomura, T.; Murata, M.; Tachibana, K.; Yasumoto, T. J. Angew. Chem., Int. Ed. Engl. 1996, 35, 5, 1672-1675.
37. (b) Nonomura, T.; Sasaki, M.; Matsumori, N.; Maruyama, T.; Murata, M.; Tachibana, K.; Yasumoto, T. J. Angew. Chem., Int. Ed. Engl. 1996, 35, 1675-1678.
38. As shown in the Supporting Information, we could easily rule out the alternative regio-isomers (6/7/7) for rings D-F, F-I, H-K, and J-M. The observed NOEs could not be explained by the distances for Me91/H32, H45/H46, H52/H55a,b, and H61/H63a, respectively. (equation presented)
39. 7).
40. 1H-1D spectrum of PAPRM2. The close chemical shifts of H37 (δ 3.08), H38 (δ 3.12), and H41 (δ 3.10), made it difficult to measure signal widths of H37 and H38. To solve the problem, signal enhancement by NOE in 1D experiment was applied. Irradiation at 2.80 ppm of the isolated H42 signal changed the signal shape of H38 to a doublet (8.5 Hz). In additional support, the H38 signal appeared as a distinct double doublet (8.5, 2.5 Hz), when protons at the bases of hydroxyl groups were shifted downfield by acetylation.
41. In the diastereomer model shown in Figure 7c, the antiperiplannar configuration for H37/H38 could not explain the observed NOEs. The distances between H37/H42 and H38/H33 were also out of NOE range. The unobserved NOE for Me91/H37 was definitely inexplicable in view of their close distance (around 2.5 Å).
42. The presence of an NOE for M91/H33 was determined from the HMQC-NOESY spectrum of NAPRM2 to avoid the proton signal overlap. Absence of the NOEs thus determined for Me91/H36a,b easily ruled out the twisted gauche rotamer in the alternative diastereomer.
43. Glendenning, L.; Igarashi, T.; Yasumoto, T. Bull. Chem. Soc. Jpn. 1996, 69, 2253-2263.
44. Clark, M.; Cramer, R. D.; Van Opdenbosch, N. J. Comput. Chem. 1989, 10, 982.
45. Dauber-Osguthorpe, P.; Robert, V. A.; Dauber-Osguthorpe, D. J.; Wolff, J.; Genest, M.; Hagler, A. T. Proteins: Struct., Func., Genet. 1988, 4, 31.
46. A weak NOE was observed for H53/H55a in the NOESY spectra of NAPRM2 and PRM2. Most probably, the intense NOE for H53/H54 was relayed to H55 in the proposed rotamer shown in Figure 9a.
47. H-H 10-11 Hz for anti H/H orientation. The intense NOE observed for H61/H63a in the NOESY of NAPRM2 also supported the presence of a gauche rotamer.
48. 1H COSY spectrum of NAMPM1.)
49. Igarashi, T.; Oshima, Y.; Murata, M.; Yasumoto, T. Harmful Marine Algal Blooms; Lassus, P., Arzul, G., Erard-LeDenn, E., Gentien, P., Marcaillou-LeBaut, C., Eds.; Lavoisier Publishing: 1994; pp 303-308.
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