(+)-Saxitoxin: A first and second generation stereoselective synthesis

Journal of the American Chemical Society

Volumn 129, Issue 32, 2007, Pages 9964-9975

  Fleming, James J ^a   McReynolds, Matthew D ^a,b   Du Bois, J ^a  

^a STANFORD UNIVERSITY   (United States)

^b PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PARALYTIC SHELLFISH; RING GUANIDINE; TRICYCLIC SKELETON;

AMINATION; AMINES; CATALYST ACTIVITY; FISH; OLEFINS; OXIDATION; SYNTHESIS (CHEMICAL); TOXIC MATERIALS;

STEREOSELECTIVITY;

CORTICOTROPIN; GUANIDINE; IMINE; NATURAL PRODUCT; NITRONE; OSMIUM; OSMIUM TRICHLORIDE; RHODIUM; SAXITOXIN; SERINE; UNCLASSIFIED DRUG;

AMINATION; ARTICLE; ASYMMETRIC SYNTHESIS; CATALYSIS; DEPROTECTION REACTION; OXIDATION; OXIDATION KINETICS; REDUCTION; SHELLFISH; STEREOSPECIFICITY; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

ALKENES; AMINES; GUANIDINES; HYDROXYLATION; SAXITOXIN; STEREOISOMERISM;

EID: 34547913768     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja071501o     Document Type: Article

References (128)

1. Fleming, J. J.; Du Bois, J. J. Am. Chem. Soc. 2006, 128, 3926-3927.
2. (a) Tanino, H.; Nakata, T.; Kaneko, T.; Kishi, Y. J. Am. Chem. Soc. 1977, 99, 2818-2819.
3. (b) Kishi, Y. Heterocycles 1980, 14, 1477-1495.
4. (c) Hong, C. Y.; Kishi, Y. J. Am. Chem. Soc. 1992, 114, 7001-7006.
5. (a) Jacobi, P. A.; Martinelli, M. J.; Polanc, S. J. Am. Chem. Soc. 1984, 106, 5594-5598.
6. (b) Martinelli, M. J.; Brownstein, A. D.; Jacobi, P. A.; Polanc, S. Croat. Chem. Acta. 1986, 59, 267-295.
7. (a) Ashcroft, F. M. Ion Channels and Disease; Academic Press: San Diego, 2000.
8. (b) Hille, B. Ion Channels of Excitable Membranes, 3rd ed.; Sinauer Associates: Sunderland, MA, 2001.
9. (a) Cestele, S.; Catterall, W. A. Biochimie 2000, 82, 883-892.
10. (b) Wang, S. Y.; Wang, G. K. Cellular Signaling 2003, 15, 151-159.
11. (c) Yamaoka, K.; Vogel, S. M.; Seyama, I. Curr. Pharm. Des. 2006, 12, 429-442.
12. Potassium and chloride ion channels have been characterized crystallographically. For recent reviews of this work, see: (a) Tombola, F.; Pathak, M. M.; Isacoff, E. Y. Annu. Rev. Cell Dev. Biol. 2006, 22, 23-52.
13. (b) Dutzler, R. Curr. Opin. Struct. Biol. 2006, 16, 439-446.
14. (c) Gouaux, E.; MacKinnon, R. Science 2005, 310, 1461-1465.
15. Schantz, E. J.; Mold, J. D.; Stanger, D. W.; Shavel, J.; Riel, F. J.; Bowden, J. P.; Lynch, J. M.; Wyler, R. S.; Riegel, B.; Sommer, H. J. Am. Chem. Soc. 1957, 79, 5230-5235.
16. (a) Schantz, E. J.; Ghazarossian, V. E.; Schnoes, H. K.; Strong, F. M.; Springer, J. P.; Pezzanite, J. O.; Clardy, J. J. Am. Chem. Soc. 1975, 97, 1238-1239.
17. (b) Bordner, J.; Thiessen, W. E.; Bates, H. A.; Rapoport, H. J. Am. Chem. Soc. 1975, 97, 6008-6012.
18. (a) Tetrodotoxin, Saxitoxin, and the Molecular Biology of the Sodium Channel; Kao, C. Y., Levinson, S. R., Eds.; Annals of the New York Academy Science: New York, 1986; Vol. 479.
19. (b) Narahashi, T. J. Toxicol., Toxin Rev. 2001, 20, 67-84.
20. (c) Novakovic, S. D.; Eglen, R. M.; Hunter, J. C. Trends Neurosci. 2001, 24, 473-478.
21. (a) Evans, M. H. Br. J. Pharmacol. Chemother. 1964, 22, 478-479.
22. (b) Kao, C. Y.; Nishiyama, A. J. Physiol. (London, U.K.) 1965, 1, 50-51.
23. (c) Kao, C. Y. Pharmacol. Rev. 1966, 2, 997-1049.
24. + channel isoforms, see: (a) Catterall, W. A.; Goldin, A. L.; Waxman, S. G. Pharmacol. Rev. 2003, 55, 575-578.
25. (b) Catterall, W. A.; Goldin, A. L.; Waxman, S. G. Pharmacol. Rev. 2005, 57, 397-409.
26. (a) Hall, S.; Strichartz, G.; Moczydlowski, E.; Ravindran, A.; Reichardt, P. B. ACS Symp. Ser. 1990, 418, 29-65.
27. (b) Yotsu-Yamashita, M. J. Toxicol., Toxin Rev. 2001, 20, 51-66.
28. (c) Llewellyn, L. E. Nat. Prod. Rep. 2006, 23, 200-222.
29. (d) Llewellyn, L.; Negri, A.; Robertson, A. J. Toxicol., Toxin Rev. 2006, 25, 159-196.
30. Kishi has prepared a small number of STX derivatives through de novo synthesis, see: Strichartz, G. R.; Hall, S.; Magnani, B.; Hong, C. Y.; Kishi, Y.; Debin, J. A. Toxicon 1995, 33, 723-737.
31. (a) Koehn, F. E.; Ghazarossian, V. E.; Schantz, E. J.; Schnoes, H. K.; Strong, F. M. Bioorg. Chem. 1981, 10, 412-428.
32. (b) Hu, S. L.; Kao, C. Y.; Koehn, F. E.; Schnoes, H. K. Toxicon 1987, 25, 159-165.
33. (c) Sato, S.; Sakai, R.; Kodama, M. Bioorg. Med. Chem. Lett. 2000, 10, 1787-1789.
34. (c) Watanabe, R.; Samusawa-Saito, R.; Oshima, Y. Bioconjugate Chem. 2006, 17, 459-465.
35. For general reviews on the synthesis of medium-sized rings, see: (a) Evans, P. A.; Holmes, A. B. Tetrahedron 1991, 47, 9131-9166.
36. (b) Yet, L. Chem. Rev. 2000, 100, 2963-3007.
37. The assembly of an eight-membered ring guanidine has been reported; however, the formation of a nine-membered ring was not possible under the same conditions, see: Fukada, N.; Takano, M.; Nakai, K.; Kuboike, S.; Takeda, Y. Bull. Chem. Soc. Jpn. 1993, 66, 148-152.
38. For the synthesis of anti-1,2-diamines, see: (a) Davis, F. A.; Deng, J. H. Org. Lett. 2004, 16, 2789-2792.
39. (b) Luo, Y.; Blaskovich, M. A.; Lajoie, G. A. J. Org. Chem. 1999, 16, 6106-6111.
40. (c) Rossi, F. M.; Powers, E. T.; Yoon, R.; Rosenberg, L.; Meinwald, J. Tetrahedron 1996, 31, 10279-10286.
41. For the initial report on the oxidative cyclization of sulfamate esters, see: Espino, C. G.; Wehn, P. M.; Chow, J.; Du Bois, J. J. Am. Chem. Soc. 2001, 28, 6935-6936.
42. Also, see: (a) Wehn, P. M.; Lee, J. H.; Du, Bois, J. Org. Lett. 2003, 25, 4823-4826.
43. (b) Wehn, P. M.; Du, Bois, J. Org. Lett. 2005, 7, 4685-4688.
44. For general reviews on C-H animation, see: (a) Espino, C. G.; Du Bois, J. In Modern Rhodium-Catalyzed Organic Reactions; Evans, P. A., Ed.; Wiley-VCH: Weinheim, 2005; pp 379-416.
45. (b) Davies, H. M. L. Angew. Chem., Int. Ed. 2006, 45, 6422-6425.
46. (c) Lebel, H.; Leogane, O.; Huard, K.; Lectard, S. Pure Appl. Chem. 2006, 78, 363-375.
47. (d) Halfen, J. A. Curr. Org. Chem. 2005, 9, 657-669.
48. (e) Müller, P.; Fruit, C. Chem. Rev. 2003, 103, 2905-2920.
49. (f) Dauban, P.; Dodd, R. H. Synlett 2003, 1571-1586.
50. Du Bois, J. CHEMTRACTS - Org. Chem. 2005, 18, 1-13.
51. Alkene aziridination using sulfamate esters has been described, see: (a) Guthikonda, K.; Du Bois, J. J. Am. Chem. Soc. 2002, 46, 13672-13673.
52. (b) Di Chenna, P. H.; Robert-Peillard, F.; Dauban, P.; Dodd, R. H. Org. Lett. 2004, 6, 4503-4505.
53. (c) Guthikonda, K.; Wehn, P. M.; Caliando, B. J.; Du Bois, J. Tetrahedron 2006, 62, 11331-11342.
54. 4 were similar. The stereochemistry of the bicyclic aziridine was not determined.
55. Nitrene insertion into an ethereal α-C-H bond parallels carbene reactivity, see: (a) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods for Organic Synthesis with Diazo Compounds: From Cyclopropanes to Ylides; Wiley and Sons, Ltd.: New York, 1997.
56. (b) Davies, H. M. L.; Beckwith, E. J. Chem. Rev. 2003, 103, 2861-2904.
57. (c) Wang, P.; Adams, J. J. Am. Chem. Soc. 1994, 116, 3296-3305.
58. (a) Fleming, J. J.; Fiori, K. W.; Du Bois, J. J. Am. Chem. Soc. 2003, 125, 2028-2029.
59. (b) Fiori, K. W.; Fleming, J. J.; Du Bois, J. Angew. Chem., Int. Ed. 2004, 43, 4349-4352.
60. (R)-(-)-2,2-Dimethyl-1,3-dioxolane-4-methanol (i.e., (R)-glycerol acetonide) was purchased from Oakwood Products Inc., West Columbia, SC 29172.
61. (R)-Glycerol acetonide can also be obtained by resolution of (±)-glycerol acetonide or from (S)-glyceraldehyde acetonide, see: (a) Pallavicini, M.; Valoti, E.; Villa, L.; Piccolo, O. Tetrahedron: Asymmetry 1994, 5, 5-8.
62. (b) Pallavicini, M.; Valoti, E.; Villa, L.; Piccolo, O. Tetrahedron: Asymmetry 1996, 7, 1117-1122.
63. (c) Hubschwerlen, C.; Specklin, J. L.; Higelin, J. Org. Synth. 1995, 72, 1-5.
64. 4, see ref 26a.
65. 2, see: Espino, C. G.; Fiori, K. W.; Kim, M.; Du Bois, J. J. Am. Chem. Soc. 2004, 126, 15378-15379.
66. (a) Handbook of Metathesis; Grubbs, R. H., Ed.; Wiley-VCH: Weinheim, 2003; Vol. 2.
67. (b) Deiters, A.; Martin, S. F. Chem. Rev. 2004, 104, 2199-2238.
68. (c) Conrad, J. C.; Fogg, D. E. Curr. Org. Chem. 2006, 10, 185-202.
69. For some recent examples, see: (a) Hirama, M.; Oishi, T.; Uehara, H.; Inoue, M.; Maruyama, M.; Guri, H.; Satake, M. Science 2001, 294, 1904-1907.
70. (b) Clark, J. S.; Marlin, F.; Nay, B.; Wilson, C. Org. Lett. 2003, 5, 89-92.
71. (c) Crimmins, M. T.; Powell, M. T. J. Am. Chem. Soc. 2003, 125, 7592-7595.
72. (d) Gaich, T.; Mulzer, J. Org. Lett. 2005, 7, 1311-1313.
73. (e Sato, K.; Sasaki, M. Org. Lett. 2005, 7, 2441-2444.
74. (f) Pansare, S. V.; Adsool, V. A. Org. Lett. 2006, 8, 5897-5899.
75. (g) Li, Y.; Hale, K. J. Org. Lett. 2007, 9, 1267-1270.
76. McReynolds, M. D., Ph.D. Thesis, University of Kansas, Lawrence, 2004.
77. Furstner, A.; Langemann, K. J. Am. Chem. Soc. 1997, 119, 9130-9136.
78. Urea 18 was synthesized from 12 following a sequence of steps analogous to those shown in Scheme 1.
79. (a) Meng, Q. C.; Hesse, M. Top. Curr. Chem. 1992, 161, 107-176.
80. (b) Parenty, A.; Moreau, X.; Campagne, J.-M. Chem. Rev. 2006, 106, 911-939.
81. For a recent comprehensive review on guanidine synthesis, see: Katritzky, A.; Rogovoy, B. V. Arkivoc 2005, 49-87.
82. Also, see: Ma, D. W.; Xia, C. F.; Jiang, J. Q.; Zhang, J. H.; Tang, W. J. J. Org. Chem. 2003, 68, 442-451.
83. Bosin, T. R.; Hanson, R. N.; Rodricks, J. V.; Simpson, R. A.; Rapoport, H. J. Org. Chem. 1973, 38, 1591-1600, and references therein.
84. To our knowledge, p-methoxybenzyl cleavage of an N-substituted oxathiazinane heterocycle or sulfamate ester has not been reported. For deprotection of an N-PMB amide, carbamate, and thiazolidinone, see respectively: (a) Williams, R. M.; Armstrong, R. W.; Dung, J. S. J. Am. Chem. Soc. 1984, 106, 5748-5750.
85. (b) Alcon, M.; Moyano, A.; Pericas, M. A.; Riera, A. Tetrahedron: Asymmetry 1999, 10, 4639-4651.
86. (c) Smith, A. B.; Leahy, J. W.; Noda, I.; Remiszewski, S. W.; Liverton, N. J.; Zibuck, R. J. Am. Chem. Soc. 1991, 114, 2995-3007.
87. For the general preparation of reagents such as 35, see: (a) Neidlein, R.; Haussman, W. Tetrahedron Lett. 1965, 1753-1755.
88. (b) Gompper, R.; Kunz, R. Chem. Ber. Recl. 1966, 99, 2900-2904.
89. (c) Merchan, F. L.; Garin, J.; Tejero, T. Synthesis 1982, 984-986.
90. Compound 35 was prepared following a published protocol, see: Tanga, M. J.; Bradford, W. W.; Bupp, J. E.; Kozocas, J. A. J. Heterocycl. Chem. 2003, 40, 569-573.
91. For examples, see: (a) Sharpless, K. B.; Lauer, R. F.; Repic, O.; Teranishi, A. Y.; Williams, D. R. J. Am. Chem. Soc. 1971, 93, 3303-3304.
92. (b) Yusubov, M. S.; Filimonov. V. D.; Vasilyeva, V. P.; Chi, K.-W. Synthesis 1995, 1234-1236.
93. (c) Yusubov, M. S.; Krasnokutskaya, E. A.; Vasilyeva, V. P.; Filimonov, V. D.; Chi, K.-W. Bull. Korean Chem. Soc. 1995, 16, 86-88.
94. (d) Clayton, M. D.; Marcinow, Z.; Rabideau, P. W. Tetrahedron Lett. 1998, 39, 9127-9130.
95. Methods for alkene ketohydroxylation have been recently reviewed, see: Plietker, B. Tetrahedron: Asymmetry 2005, 16, 3453-3459.
96. Also, see: Plietker, B. Synthesis 2005, 2453-2472.
97. (a) Calculations performed using Gaussian 03, Revision C.02, Frisch, M. J. et al. Gaussian, Inc., Wallingford, CT, 2004.
98. (b) Becke, A. D. J. Chem. Phys. 1993, 98, 5648-5652.
99. The conditions employed were analogous to those described for olefin dihydroxylation, see: (a) Plietker, B.; Niggemann, M. Org. Lett. 2003, 5, 3353-3356.
100. (b) Plietker, B.; Niggemann, M.; Pollrich, A. Org. Biomol. Chem. 2004, 2, 1116-1124.
101. X-ray analysis was performed on the p-toluenesulfonyl-protected form of 44. The tosyl-protecting group was employed in our earliest studies to prepare STX and later replaced with p-methoxybenzenesulfonyl (Mbs).
102. 4 for alkene ketohydroxylation, see: (a) Plietker, B. J. Org. Chem. 2003, 68, 7123-7125.
103. (b) Plietker, B. J. Org. Chem. 2004, 69, 8287-8296.
104. (c) Plietker, B. Eur. J. Org. Chem. 2005, 1919-1929.
105. 1H NMR spectrum of this product made difficult an accurate determination of the relative amount of the minor isomer.
106. 13C NMR. For examples of guanidine-derived structures possessing a hydrated ketone, see: Houghten, R. A.; Simpson, R. A.; Hanson, R. N.; Rapoport, H. J. Org. Chem. 1979, 44, 4536-4543.
107. Complete HMBC data for compound 48 can be found in the Supporting Information.
108. 1H NMR and mass spectral analysis, is tentative.
109. Although the undesired hemiaminal 54 formed as a single diastereomer, its stereochemistry was never established conclusively.
110. It is not possible to discount a mechanistic scenario in which rapid tautomerization of the α-ketol isomers precedes transannular ring closure. We believe, however, mat the collective results of our studies to oxidize substrates such as 51 are more consistent with an oxidation reaction in which α-ketol selectivity is kinetically controlled.
111. (a) Pless, J.; Bauer, W. Angew. Chem., Int. Ed. 1973, 12, 147-148.
112. (b) Nishimura, O.; Fujino, M. Chem. Pharm. Bull. 1976, 24, 1568-1575.
113. Kocovsky, P. Tetrahedron Lett. 1986, 27, 5521-5524.
114. For a discussion of C-C bond cleavage by Ru and Os oxidants, see: Frunzke, J.; Loschen, C.; Frenking, G. J. Am. Chem. Soc. 2004, 126, 3642-3652.
115. (a) Prins, D. A; Reichstein, T. Helv. Chim. Acta 1942, 25, 300-322.
116. (b) Miescher, K. Helv. Chim. Acta 1950, 6, 1840-1847.
117. (c) Miescher, K.; Schmidlin, R.; Schmidlin, J. U.S. Patent 2,668,816, 1954.
118. Harkema, J. U.S. Patent 3,582,270, June 1, 1971, and references cited therein.
119. (a) VanRheenen, V.; Kelly, R. C.; Cha, D. Y. Tetrahedron Lett. 1976, 23, 1973-1976.
120. (b) Lohray, B. B.; Bhushan, V.; Kumar, R. K. J. Org. Chem. 1994, 6, 1375-1380.
121. 3 with peracetic acid in EtOAc for α-ketol formation. We did not investigate these specific conditions due to the inability to obtain a commercial supply of peracetic acid in EtOAc.
122. 3 and Oxone leads to the formation of an Os(V)=O species, which serves as the operative oxidant. The pendant guanidine at C5 may have a critical role as a base to promote selective elimination from the C4 center. Studies are on-going to explore the mechanistic details of this process and will be reported in due course.
123. Pfitzner, K. E.; Moffatt, J. G. J. Am. Chem. Soc. 1965, 87, 5661-5670.
124. Moran, O.; Picollo, A.; Conti, F. Biophys. J. 2003, 5, 2999-3066.
125. (a) Merino, P.; Franco, S.; Merchan, F. L.; Tejero, T. Synlett 2000, 442-454, and references cited therein.
126. (b) Merino, P.; Franco, S.; Merchan, F. L.; Tejero, T. J. Org. Chem. 1998, 16, 5627-5630.
127. Merino, P.; Lanaspa, A.; Merchan, F. L.; Tejero, T. Tetrahedron: Asymmetry 1998, 4, 629-646.
128. All attempts to add the zinc acetylide of 63 to oxathiazinane 10 (see Figure 10) were unsuccessful.