Structure-activity studies on anticonvulsant sugar sulfamates related to topiramate. Enhanced potency with cyclic sulfate derivatives

Journal of Medicinal Chemistry

Volumn 41, Issue 8, 1998, Pages 1315-1343

  Maryanoff, Bruce E ^a   Costanzo, Michael J ^a   Nortey, Samuel O ^a   Greco, Michael N ^a   Shank, Richard P ^a   Schupsky, James J ^a   Ortegon, Marta P ^a   Vaught, Jeffry L ^a  

^a R W JOHNSON PHARMACEUTICAL RES I   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2,3 O (ISOPROPYLIDENE) 4,5 O SULFONYL BETA D FRUCTOPYRANOSE METHYLSULFAMATE; ANTICONVULSIVE AGENT; TOPIRAMATE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTICONVULSANT ACTIVITY; ARTICLE; CRYSTAL STRUCTURE; DRUG CONFORMATION; DRUG POTENCY; DRUG SYNTHESIS; EPILEPSY; HYDROGEN BOND; INTRAPERITONEAL DRUG ADMINISTRATION; MOLECULAR INTERACTION; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION;

ANIMALS; ANTICONVULSANTS; CARBONIC ANHYDRASE INHIBITORS; CRYSTALLOGRAPHY, X-RAY; ELECTROSHOCK; FRUCTOSE; MICE; MOLECULAR CONFORMATION; RATS; SEIZURES; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONIC ACIDS;

EID: 0032499217     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970790w     Document Type: Article

References (132)

1. For recent reviews on epilepsy and antiepileptic drugs, see: (a) Rogawski, M. A.; Porter, R. J. Antiepileptic Drugs: Pharmaco-logical Mechanisms and Clinical Efficacy with Consideration of Promising Developmental Stage Compounds. Pharmacol. Rev. 1990, 42, 223-285. (b) Löscher, W.; Schmidt, D. Strategies in Antiepileptic Drug Development: Is Rational Drug Design Superior to Random Screening and Structure Variation? Epilepsy Res. 1994, 17, 95-134. (c) Patsalos, P. N.; Duncan, J. S. New Antiepileptic Drugs: A Review of Their Current Status and Clinical Potential. CNS Drugs 1994, 2, 40-77. (d) Britton, J. W.; So, E. L. New Antiepileptic Drugs: Prospects for the Future. J. Epilepsy 1995, 8, 267-281. (e) Fisher, R.; Blum, D. Clobazam, Oxcarbazepine, Tiagabine, Topiramate, and Other New Antiepileptic Drugs. Epilepsia 1995, 36 (S2), S105-114. (f) Dichter, M. A.; Brodie, M. J. New Antiepileptic Drugs. N. Engl. J. Med. 1996, 334, 1583-1590. (g) Levy, R. H.; Mattson, R. H., Meldrum, B. S., Eds. Antiepileptic Drugs, 4th ed.; Raven Press: New York, 1995. (h) Benetello, P. New Antiepileptic Drugs. Pharmacol. Res. 1995, 31, 155-162. Trimble, M. R. New Anticonvulsants: Advances in the Treatment of Epilepsy; Wiley: New York, 1994. (j) Marson, A. G.; Kadir, Z. A.; Chadwick, D. W. New Antiepileptic Drugs: A Systematic Review of Their Efficacy and Tolerability. Br. Med. J. 1996, 313 (7066), 1169-1174.
2. For recent reviews on epilepsy and antiepileptic drugs, see: (a) Rogawski, M. A.; Porter, R. J. Antiepileptic Drugs: Pharmaco-logical Mechanisms and Clinical Efficacy with Consideration of Promising Developmental Stage Compounds. Pharmacol. Rev. 1990, 42, 223-285. (b) Löscher, W.; Schmidt, D. Strategies in Antiepileptic Drug Development: Is Rational Drug Design Superior to Random Screening and Structure Variation? Epilepsy Res. 1994, 17, 95-134. (c) Patsalos, P. N.; Duncan, J. S. New Antiepileptic Drugs: A Review of Their Current Status and Clinical Potential. CNS Drugs 1994, 2, 40-77. (d) Britton, J. W.; So, E. L. New Antiepileptic Drugs: Prospects for the Future. J. Epilepsy 1995, 8, 267-281. (e) Fisher, R.; Blum, D. Clobazam, Oxcarbazepine, Tiagabine, Topiramate, and Other New Antiepileptic Drugs. Epilepsia 1995, 36 (S2), S105-114. (f) Dichter, M. A.; Brodie, M. J. New Antiepileptic Drugs. N. Engl. J. Med. 1996, 334, 1583-1590. (g) Levy, R. H.; Mattson, R. H., Meldrum, B. S., Eds. Antiepileptic Drugs, 4th ed.; Raven Press: New York, 1995. (h) Benetello, P. New Antiepileptic Drugs. Pharmacol. Res. 1995, 31, 155-162. Trimble, M. R. New Anticonvulsants: Advances in the Treatment of Epilepsy; Wiley: New York, 1994. (j) Marson, A. G.; Kadir, Z. A.; Chadwick, D. W. New Antiepileptic Drugs: A Systematic Review of Their Efficacy and Tolerability. Br. Med. J. 1996, 313 (7066), 1169-1174.
3. For recent reviews on epilepsy and antiepileptic drugs, see: (a) Rogawski, M. A.; Porter, R. J. Antiepileptic Drugs: Pharmaco-logical Mechanisms and Clinical Efficacy with Consideration of Promising Developmental Stage Compounds. Pharmacol. Rev. 1990, 42, 223-285. (b) Löscher, W.; Schmidt, D. Strategies in Antiepileptic Drug Development: Is Rational Drug Design Superior to Random Screening and Structure Variation? Epilepsy Res. 1994, 17, 95-134. (c) Patsalos, P. N.; Duncan, J. S. New Antiepileptic Drugs: A Review of Their Current Status and Clinical Potential. CNS Drugs 1994, 2, 40-77. (d) Britton, J. W.; So, E. L. New Antiepileptic Drugs: Prospects for the Future. J. Epilepsy 1995, 8, 267-281. (e) Fisher, R.; Blum, D. Clobazam, Oxcarbazepine, Tiagabine, Topiramate, and Other New Antiepileptic Drugs. Epilepsia 1995, 36 (S2), S105-114. (f) Dichter, M. A.; Brodie, M. J. New Antiepileptic Drugs. N. Engl. J. Med. 1996, 334, 1583-1590. (g) Levy, R. H.; Mattson, R. H., Meldrum, B. S., Eds. Antiepileptic Drugs, 4th ed.; Raven Press: New York, 1995. (h) Benetello, P. New Antiepileptic Drugs. Pharmacol. Res. 1995, 31, 155-162. Trimble, M. R. New Anticonvulsants: Advances in the Treatment of Epilepsy; Wiley: New York, 1994. (j) Marson, A. G.; Kadir, Z. A.; Chadwick, D. W. New Antiepileptic Drugs: A Systematic Review of Their Efficacy and Tolerability. Br. Med. J. 1996, 313 (7066), 1169-1174.
4. For recent reviews on epilepsy and antiepileptic drugs, see: (a) Rogawski, M. A.; Porter, R. J. Antiepileptic Drugs: Pharmaco-logical Mechanisms and Clinical Efficacy with Consideration of Promising Developmental Stage Compounds. Pharmacol. Rev. 1990, 42, 223-285. (b) Löscher, W.; Schmidt, D. Strategies in Antiepileptic Drug Development: Is Rational Drug Design Superior to Random Screening and Structure Variation? Epilepsy Res. 1994, 17, 95-134. (c) Patsalos, P. N.; Duncan, J. S. New Antiepileptic Drugs: A Review of Their Current Status and Clinical Potential. CNS Drugs 1994, 2, 40-77. (d) Britton, J. W.; So, E. L. New Antiepileptic Drugs: Prospects for the Future. J. Epilepsy 1995, 8, 267-281. (e) Fisher, R.; Blum, D. Clobazam, Oxcarbazepine, Tiagabine, Topiramate, and Other New Antiepileptic Drugs. Epilepsia 1995, 36 (S2), S105-114. (f) Dichter, M. A.; Brodie, M. J. New Antiepileptic Drugs. N. Engl. J. Med. 1996, 334, 1583-1590. (g) Levy, R. H.; Mattson, R. H., Meldrum, B. S., Eds. Antiepileptic Drugs, 4th ed.; Raven Press: New York, 1995. (h) Benetello, P. New Antiepileptic Drugs. Pharmacol. Res. 1995, 31, 155-162. Trimble, M. R. New Anticonvulsants: Advances in the Treatment of Epilepsy; Wiley: New York, 1994. (j) Marson, A. G.; Kadir, Z. A.; Chadwick, D. W. New Antiepileptic Drugs: A Systematic Review of Their Efficacy and Tolerability. Br. Med. J. 1996, 313 (7066), 1169-1174.
5. For recent reviews on epilepsy and antiepileptic drugs, see: (a) Rogawski, M. A.; Porter, R. J. Antiepileptic Drugs: Pharmaco-logical Mechanisms and Clinical Efficacy with Consideration of Promising Developmental Stage Compounds. Pharmacol. Rev. 1990, 42, 223-285. (b) Löscher, W.; Schmidt, D. Strategies in Antiepileptic Drug Development: Is Rational Drug Design Superior to Random Screening and Structure Variation? Epilepsy Res. 1994, 17, 95-134. (c) Patsalos, P. N.; Duncan, J. S. New Antiepileptic Drugs: A Review of Their Current Status and Clinical Potential. CNS Drugs 1994, 2, 40-77. (d) Britton, J. W.; So, E. L. New Antiepileptic Drugs: Prospects for the Future. J. Epilepsy 1995, 8, 267-281. (e) Fisher, R.; Blum, D. Clobazam, Oxcarbazepine, Tiagabine, Topiramate, and Other New Antiepileptic Drugs. Epilepsia 1995, 36 (S2), S105-114. (f) Dichter, M. A.; Brodie, M. J. New Antiepileptic Drugs. N. Engl. J. Med. 1996, 334, 1583-1590. (g) Levy, R. H.; Mattson, R. H., Meldrum, B. S., Eds. Antiepileptic Drugs, 4th ed.; Raven Press: New York, 1995. (h) Benetello, P. New Antiepileptic Drugs. Pharmacol. Res. 1995, 31, 155-162. Trimble, M. R. New Anticonvulsants: Advances in the Treatment of Epilepsy; Wiley: New York, 1994. (j) Marson, A. G.; Kadir, Z. A.; Chadwick, D. W. New Antiepileptic Drugs: A Systematic Review of Their Efficacy and Tolerability. Br. Med. J. 1996, 313 (7066), 1169-1174.
6. For recent reviews on epilepsy and antiepileptic drugs, see: (a) Rogawski, M. A.; Porter, R. J. Antiepileptic Drugs: Pharmaco-logical Mechanisms and Clinical Efficacy with Consideration of Promising Developmental Stage Compounds. Pharmacol. Rev. 1990, 42, 223-285. (b) Löscher, W.; Schmidt, D. Strategies in Antiepileptic Drug Development: Is Rational Drug Design Superior to Random Screening and Structure Variation? Epilepsy Res. 1994, 17, 95-134. (c) Patsalos, P. N.; Duncan, J. S. New Antiepileptic Drugs: A Review of Their Current Status and Clinical Potential. CNS Drugs 1994, 2, 40-77. (d) Britton, J. W.; So, E. L. New Antiepileptic Drugs: Prospects for the Future. J. Epilepsy 1995, 8, 267-281. (e) Fisher, R.; Blum, D. Clobazam, Oxcarbazepine, Tiagabine, Topiramate, and Other New Antiepileptic Drugs. Epilepsia 1995, 36 (S2), S105-114. (f) Dichter, M. A.; Brodie, M. J. New Antiepileptic Drugs. N. Engl. J. Med. 1996, 334, 1583-1590. (g) Levy, R. H.; Mattson, R. H., Meldrum, B. S., Eds. Antiepileptic Drugs, 4th ed.; Raven Press: New York, 1995. (h) Benetello, P. New Antiepileptic Drugs. Pharmacol. Res. 1995, 31, 155-162. Trimble, M. R. New Anticonvulsants: Advances in the Treatment of Epilepsy; Wiley: New York, 1994. (j) Marson, A. G.; Kadir, Z. A.; Chadwick, D. W. New Antiepileptic Drugs: A Systematic Review of Their Efficacy and Tolerability. Br. Med. J. 1996, 313 (7066), 1169-1174.
7. For recent reviews on epilepsy and antiepileptic drugs, see: (a) Rogawski, M. A.; Porter, R. J. Antiepileptic Drugs: Pharmaco-logical Mechanisms and Clinical Efficacy with Consideration of Promising Developmental Stage Compounds. Pharmacol. Rev. 1990, 42, 223-285. (b) Löscher, W.; Schmidt, D. Strategies in Antiepileptic Drug Development: Is Rational Drug Design Superior to Random Screening and Structure Variation? Epilepsy Res. 1994, 17, 95-134. (c) Patsalos, P. N.; Duncan, J. S. New Antiepileptic Drugs: A Review of Their Current Status and Clinical Potential. CNS Drugs 1994, 2, 40-77. (d) Britton, J. W.; So, E. L. New Antiepileptic Drugs: Prospects for the Future. J. Epilepsy 1995, 8, 267-281. (e) Fisher, R.; Blum, D. Clobazam, Oxcarbazepine, Tiagabine, Topiramate, and Other New Antiepileptic Drugs. Epilepsia 1995, 36 (S2), S105-114. (f) Dichter, M. A.; Brodie, M. J. New Antiepileptic Drugs. N. Engl. J. Med. 1996, 334, 1583-1590. (g) Levy, R. H.; Mattson, R. H., Meldrum, B. S., Eds. Antiepileptic Drugs, 4th ed.; Raven Press: New York, 1995. (h) Benetello, P. New Antiepileptic Drugs. Pharmacol. Res. 1995, 31, 155-162. Trimble, M. R. New Anticonvulsants: Advances in the Treatment of Epilepsy; Wiley: New York, 1994. (j) Marson, A. G.; Kadir, Z. A.; Chadwick, D. W. New Antiepileptic Drugs: A Systematic Review of Their Efficacy and Tolerability. Br. Med. J. 1996, 313 (7066), 1169-1174.
8. For recent reviews on epilepsy and antiepileptic drugs, see: (a) Rogawski, M. A.; Porter, R. J. Antiepileptic Drugs: Pharmaco-logical Mechanisms and Clinical Efficacy with Consideration of Promising Developmental Stage Compounds. Pharmacol. Rev. 1990, 42, 223-285. (b) Löscher, W.; Schmidt, D. Strategies in Antiepileptic Drug Development: Is Rational Drug Design Superior to Random Screening and Structure Variation? Epilepsy Res. 1994, 17, 95-134. (c) Patsalos, P. N.; Duncan, J. S. New Antiepileptic Drugs: A Review of Their Current Status and Clinical Potential. CNS Drugs 1994, 2, 40-77. (d) Britton, J. W.; So, E. L. New Antiepileptic Drugs: Prospects for the Future. J. Epilepsy 1995, 8, 267-281. (e) Fisher, R.; Blum, D. Clobazam, Oxcarbazepine, Tiagabine, Topiramate, and Other New Antiepileptic Drugs. Epilepsia 1995, 36 (S2), S105-114. (f) Dichter, M. A.; Brodie, M. J. New Antiepileptic Drugs. N. Engl. J. Med. 1996, 334, 1583-1590. (g) Levy, R. H.; Mattson, R. H., Meldrum, B. S., Eds. Antiepileptic Drugs, 4th ed.; Raven Press: New York, 1995. (h) Benetello, P. New Antiepileptic Drugs. Pharmacol. Res. 1995, 31, 155-162. Trimble, M. R. New Anticonvulsants: Advances in the Treatment of Epilepsy; Wiley: New York, 1994. (j) Marson, A. G.; Kadir, Z. A.; Chadwick, D. W. New Antiepileptic Drugs: A Systematic Review of Their Efficacy and Tolerability. Br. Med. J. 1996, 313 (7066), 1169-1174.
9. For recent reviews on epilepsy and antiepileptic drugs, see: (a) Rogawski, M. A.; Porter, R. J. Antiepileptic Drugs: Pharmaco-logical Mechanisms and Clinical Efficacy with Consideration of Promising Developmental Stage Compounds. Pharmacol. Rev. 1990, 42, 223-285. (b) Löscher, W.; Schmidt, D. Strategies in Antiepileptic Drug Development: Is Rational Drug Design Superior to Random Screening and Structure Variation? Epilepsy Res. 1994, 17, 95-134. (c) Patsalos, P. N.; Duncan, J. S. New Antiepileptic Drugs: A Review of Their Current Status and Clinical Potential. CNS Drugs 1994, 2, 40-77. (d) Britton, J. W.; So, E. L. New Antiepileptic Drugs: Prospects for the Future. J. Epilepsy 1995, 8, 267-281. (e) Fisher, R.; Blum, D. Clobazam, Oxcarbazepine, Tiagabine, Topiramate, and Other New Antiepileptic Drugs. Epilepsia 1995, 36 (S2), S105-114. (f) Dichter, M. A.; Brodie, M. J. New Antiepileptic Drugs. N. Engl. J. Med. 1996, 334, 1583-1590. (g) Levy, R. H.; Mattson, R. H., Meldrum, B. S., Eds. Antiepileptic Drugs, 4th ed.; Raven Press: New York, 1995. (h) Benetello, P. New Antiepileptic Drugs. Pharmacol. Res. 1995, 31, 155-162. Trimble, M. R. New Anticonvulsants: Advances in the Treatment of Epilepsy; Wiley: New York, 1994. (j) Marson, A. G.; Kadir, Z. A.; Chadwick, D. W. New Antiepileptic Drugs: A Systematic Review of Their Efficacy and Tolerability. Br. Med. J. 1996, 313 (7066), 1169-1174.
10. For recent reviews on epilepsy and antiepileptic drugs, see: (a) Rogawski, M. A.; Porter, R. J. Antiepileptic Drugs: Pharmaco-logical Mechanisms and Clinical Efficacy with Consideration of Promising Developmental Stage Compounds. Pharmacol. Rev. 1990, 42, 223-285. (b) Löscher, W.; Schmidt, D. Strategies in Antiepileptic Drug Development: Is Rational Drug Design Superior to Random Screening and Structure Variation? Epilepsy Res. 1994, 17, 95-134. (c) Patsalos, P. N.; Duncan, J. S. New Antiepileptic Drugs: A Review of Their Current Status and Clinical Potential. CNS Drugs 1994, 2, 40-77. (d) Britton, J. W.; So, E. L. New Antiepileptic Drugs: Prospects for the Future. J. Epilepsy 1995, 8, 267-281. (e) Fisher, R.; Blum, D. Clobazam, Oxcarbazepine, Tiagabine, Topiramate, and Other New Antiepileptic Drugs. Epilepsia 1995, 36 (S2), S105-114. (f) Dichter, M. A.; Brodie, M. J. New Antiepileptic Drugs. N. Engl. J. Med. 1996, 334, 1583-1590. (g) Levy, R. H.; Mattson, R. H., Meldrum, B. S., Eds. Antiepileptic Drugs, 4th ed.; Raven Press: New York, 1995. (h) Benetello, P. New Antiepileptic Drugs. Pharmacol. Res. 1995, 31, 155-162. Trimble, M. R. New Anticonvulsants: Advances in the Treatment of Epilepsy; Wiley: New York, 1994. (j) Marson, A. G.; Kadir, Z. A.; Chadwick, D. W. New Antiepileptic Drugs: A Systematic Review of Their Efficacy and Tolerability. Br. Med. J. 1996, 313 (7066), 1169-1174.
11. (a) Maryanoff, B. E.; Nortey, S. O.; Gardocki, J. F.; Shank, R. P.; Dodgson, S. P. Anticonvulsant O-Alkyl Sulfamates. 2,3:4,5-Bis-O-(1-methylethylidene)-β-D-fructopyranose Sulfamate and Related Compounds. J. Med. Chem. 1987, 30, 880-887.
12. (b) Shank, R. P.; Gardocki, J. F.; Vaught, J. L.; Davis, C. B.; Schupsky, J. J.; Raffa, R. B.; Dodgson, S. J.; Nortey, S. O.; Maryanoff, B. E. Topiramate: Preclinical Evaluation of a Structurally Novel Anticonvulsant. Epilepsia 1994, 35, 450-460.
13. (a) Maryanoff, B. E.; Margul, B. L. Topiramate. Drugs Future 1989, 14, 342-344.
14. (b) Follow-up reviews: Anon. Ibid. 1993, 18, 397-398. Anon. Ibid. 1994, 19, 425. Anon. Ibid. 1995, 20, 444-445. Anon. Ibid. 1997, 22, 458-460.
15. (b) Follow-up reviews: Anon. Ibid. 1993, 18, 397-398. Anon. Ibid. 1994, 19, 425. Anon. Ibid. 1995, 20, 444-445. Anon. Ibid. 1997, 22, 458-460.
16. (b) Follow-up reviews: Anon. Ibid. 1993, 18, 397-398. Anon. Ibid. 1994, 19, 425. Anon. Ibid. 1995, 20, 444-445. Anon. Ibid. 1997, 22, 458-460.
17. (b) Follow-up reviews: Anon. Ibid. 1993, 18, 397-398. Anon. Ibid. 1994, 19, 425. Anon. Ibid. 1995, 20, 444-445. Anon. Ibid. 1997, 22, 458-460.
18. (c) Perucca, E. A Pharmacological and Clinical Review on Topiramate, a New Antiepileptic Drug. Pharmacol. Res. 1997, 35, 241-256.
19. (d) Langtry, H. D.; Gillis, J. C.; Davis, R. Topiramate: A Review of its Pharmaco-dynamic and Pharmacokinetic Properties and Clinical Efficacy in the Management of Epilepsy. Drugs 1997, 54, 752-773.
20. (e) Privitera, M. D. Topiramate: A New Antiepileptic Drug. Ann. Pharmacother. 1997, 31, 1164-1173.
21. (f) Ben-Menachem, E. Topiramate: Current Status and Therapeutic Potential. Expert Opin. Invest. Drugs 1997, 6, 1085-1094.
22. (g) Rosenfeld, W. E. Topiramate - A Review of Preclinical, Pharmacokinetic, and Clinical Data. Clin. Ther. 1997, 19, 1294-1308.
23. For a preliminary communication, see: Maryanoff, B. E.; Costanzo, M. J.; Shank, R. P.; Schupsky, J. J.; Ortegon, M. E.; Vaught, J. L. Anticonvulsant Sugar Sulfamates. Potent Cyclic Sulfate and Cyclic Sulfite Analogues of Topiramate. Bioorg. Med. Chem. Lett. 1993, 3, 2653-2656.
24. Reitz, A. B.; Tuman, R. W.; Marchione, C. S.; Jordan, A. D., Jr.; Bowden, C. R.; Maryanoff, B. E. Carbohydrate Biguanides as Potential Hypoglycemic Agents. J. Med. Chem. 1989, 32, 2110-2116.
25. Brady, R. F., Jr. Cyclic Acetals of Ketoses. III. Reinvestigation of the Synthesis of the Isomeric Di-O-isopropylidene-β-D-fructopyranoses. Carbohydr. Res. 1970, 15, 35-40.
26. (a) Yu, D.; d'Alarco, M. Synthesis of 3′-Cyano-2′,3′-dideoxyadenosine and 2′,3′-Dideoxy-3′-formyl-adenosine. J. Org. Chem. 1989, 54, 3240-3242.
27. (b) Iodide 12 has been reported, e.g.: James, K.; Angyal, S. J. New Syntheses of 1-Deoxyhexuloses. Aust. J. Chem. 1972, 25, 1967-1977. Binkley, R. W.; Hehemann, D. G. New Synthesis of Deoxyiodo Sugars. J. Org. Chem. 1978, 43, 3244-3245.
28. (b) Iodide 12 has been reported, e.g.: James, K.; Angyal, S. J. New Syntheses of 1-Deoxyhexuloses. Aust. J. Chem. 1972, 25, 1967-1977. Binkley, R. W.; Hehemann, D. G. New Synthesis of Deoxyiodo Sugars. J. Org. Chem. 1978, 43, 3244-3245.
29. (a) Arrick, R. E.; Baker, D. C.; Horton, D. Chromium Trioxide-Dipyridine Complex as an Oxidant for Partially Protected Sugars. Preparation of Aldehydo and Certain Keto Sugar Derivatives. Carbohydr. Res. 1973, 26, 441-447.
30. (b) Lowe, R. W.; Szarek, W. A.; Jones, J. K. N. Conversion of 2-Hexuloses into 3-Heptuloses. Synthesis of D-Manno-3-heptulose. Carbohydr. Res. 1973, 28, 281-293.
31. (c) Heathcock, C. H.; White, C. T.; Morrison, J. J.; VanDerveer, D. Acyclic Stereoselection. 11. Double Stereodifferentiation as a Method for Achieving Superior Cram's Rule Selectivity in Aldol Condensations with Chiral Aldehydes. J. Org. Chem. 1981, 46, 1296-1309.
32. 2, proved to be unrewarding.
33. (b) Omura, K.; Swern, D. Oxidation of Alcohols by "Activated" Dimethyl Sulfoxide. A Preparative Steric and Mechanistic Study. Tetrahedron 1978, 34, 1651-1660.
34. (a) Carretero, J. C.; Demillequand, M.; Ghosez, L. Synthesis of α,β-Unsaturated Sulfonates via the Wittig-Horner Reaction. Tetrahedron 1987, 43, 5125-5134.
35. 3Ph from phenyl methanesulfonate failed.
36. (a) Izquierdo, I.; Plaza, M. T.; Robles, R.; Rodriguez, C. A Highly Diastereoselective Preparation of 4-Octulose and 2-Deoxy-4-octulose from a D-Fructose Derivative. Tetrahedron: Asymmetry 1996, 7, 3593-3604.
37. (b) Izquierdo, Isidoro; Plaza, Maria T. Synthesis of 4-Octuloses from a Derivative of D-Fructose. J. Carbohydr. Chem. 1996, 15, 303-315.
38. (a) Cubero, I. I.; Lopez-Espinosa, M. T. P.; Richardson, A. C.; Aamlid, K. H. Enantiospecific Synthesis of Spiroacetals. Part IV. Enantiospecific Synthesis of (R)-1,6-Dioxaspiro[4.5]decane from a Derivative of D-Fructose. Carbohydr. Res. 1993, 242, 281-286.
39. (b) Aamlid, K. H.; Hough, L.; Richardson, A. C. Enantiospecific Synthesis of Polyhydroxylated Indolizidines Related to Castanospermine. Part III. Synthesis of 1-Deoxy-6-epicastano-spermine and 1-Deoxy-6/8a-diepi-Castanospermine. Ibid. 1990, 202, 117-129.
40. (a) Note: Pertaining to ref 8c, the configuration at C1 for the carbanion addition products from aldehyde 15 (including 21a) is actually not established, contrary to what is shown pictorially in that paper (Heathcock, C. H., personal communication, 1997).
41. (b) Martinez, E.; Gonzalez, A.; Echavarren, D. Synthesis of Derivatives from Acetonide of D-Galactose and D-Fructose. An. Quim., Ser. C 1980, 76, 230-232 (CAN 95: 81334).
42. 2-t-Bu to 15 was assigned the R configuration by chemical correlation; see: Izquierdo, I.; Plaza, M. T.; Robles, R.; Mota, A. Synthesis of 2-Deoxy-4-octulose Derivatives by Highly Diastereoselective Alkylations of Protected Hexuloses. Tetrahedron: Asymmetry 1997, 8, 2597-2606.
43. We also prepared a series of sulfonyl imidate derivatives of 1 as potential prodrugs: Maryanoff, B. E. U.S. Patent 5,258,402, 1993.
44. Barnett, J. E. G.; Atkins, G. R. S. Preparation of 1-Deoxy-1-haloD-fructoses. Carbohydr. Res. 1972, 25, 511-515.
45. Kim, K. S.; Szarek, W. A. Methylenation of Carbohydrates using Phase-Transfer Catalysis. Synthesis 1978, 48-50.
46. (a) Wolfrom, M. L.; Lew, B. W.; Max Goepp, R. J. Sugar Interconversion under Reducing Conditions. J. Am. Chem. Soc. 1946, 68, 1443-1148.
47. (b) Bourne, E. J.; Wiggins, L. F. The Constitution of Trimethylene Sorbitol. J. Chem. Soc. 1944, 517-521.
48. Desulfurization of 53 with Raney nickel in refluxing EtOH/benzene (Foster, A. B.; Wolfrom, M. L. An Anolmalous Reaction of Methyl 3,4-O-Isopropylidene-β-D-arabmopyranose-2-O-(S-Sodium Dithiocarbonate). J. Am. Chem. Soc. 1956, 78, 2493-2495) gave a trace of 32 along with decomposed material.
49. 2 the hydrolysis product from 39 contained unreacted starting material and fully deketalized tetraol (43% yield), in addition to desired 40 (23% yield).
50. Debenzylation of 41 did not occur with hydrogen (50 psig) and 10% Pd/C nor with hydrazine and 10% Pd/C in refluxing methanol.
51. Niaz, G. R.; Reese, C. B. Ribonucleoside 2′,3′-Orthocarbonates. J. Chem. Soc., Chem. Commun. 1969, 552-553.
52. Eliel, E. L.; Wilen, S. H.; Mander, L. N. Stereochemistry of Organic Compounds; Wiley: New York, 1994.
53. An optimal log P value for CNS active compounds is 2.0, although compounds within the range of 0-4.0 can be effective. See: Hansch, C.; Leo, A. Exploring QSAR Fundamentals and Applications in Chemistry and Biology; American Chemical Society: Washington, DC, 1995.
54. Delavarenne, S. Y. U.S. Patent 3,795,682, 1974.
55. Hartmann, L. A. U.S. Patent 3,741,986, 1973.
56. Martin, O. R.; Korppi-Tommola, S. L.; Szarek, W. A. Structure-Sweetness Relationships for Fructose Analogs. Part I. Synthesis and Evaluation of Sweetness of 5-Deoxy-D-threo-hexulose. Can. J. Chem. 1982, 60, 1857-1862.
57. (a) Van Cauwenberghe, R.; Anteunis, M.; Becu, C. Preparation of 2-Haloalkyl Substituted 1,3-Dioxolanes and 1,3-Dioxanes. J. Fluorine Chem. 1975, 5, 277-291.
58. (b) Coe, D. G.; Pattison, D. B. U.S. Patent 3,324,144, 1967.
59. The benzyl protecting group was used on the C1 hydroxyl because hexafluoroacetone could form an adduct with the hydroxyl to impede the desired reaction pathway.
60. Costanzo, M. J.; Almond, H. R., Jr.; Gauthier, D.; Maryanoff, B. E. Non-Chair Six-Membered-Ring Conformations, Preference for a Twist-Boat (or Skew) Structure in Alpha-L-Sorbopyranose Derivatives. Tetrahedron: Asymmetry 1994, 5, 2459-2473.
61. Bourne, E. J.; Lees, E. M.; Weigel, H. Phenylboronates of Acyclic Polyhydroxy-compounds. J. Chem. Soc. 1965, 3798-3802.
62. Cubero, I. I.; Lopez-Espinosa, M. T. P. Synthetic Application of Partially Protected Fructopyranoses. J. Carbohydr. Res. 1986, 5, 299-311.
63. 2,6
64. Koerner, T. A. W., Jr.; Younathan, E. S.; Wander, J. D. Elucidation of the Structure of Dibenzylidene Fructose by Physical Methods and Use of a Shift Reagent. Carbohydr. Res. 1972, 21, 455-459.
65. 5 (δ 4.35, dd).
66. Corey, E. J.; Winter, R. A. E. A New Stereospecific Olefin Synthesis from 1,2-Diols. J. Am. Chem. Soc. 1963, 85, 2677-2678.
67. Dudycz, L. W. Synthesis of 2′,3′-Dideoxyuridine via the Corey-Winter reaction. Nucleosides Nucleotides 1989, 8, 35-41.
68. Corey, E. J.; Hopkins, P. B. A Mild Procedure for the Conversion of 1,2-Diols to Olefins. Tetrahedron Lett. 1982, 23, 1979-1882.
69. Daub, J.; Trautz, V.; Erhardt, U. Olefin Synthesis with Iron Pentacarbonyl. Tetrahedron Lett. 1972, 4435-4438.
70. Semmelhack, M. F.; Stauffer, R. D. Synthesis with Zerovalent Metals. Conversion of Thionocarbonates to Alkenes with Bis(1,5-cyclooctadiene)nickel(0). Tetrahedron Lett. 1973, 2667-2670.
71. (a) Vedejs, E.; Wu, E. S. C. Synthesis of Olefins from Thiono-carbonates by an Alkylation-Reduction Sequence. J. Org. Chem. 1974, 39, 3641-3644.
72. (b) Barton, D. H. R.; Stick, R. V. Reaction of Diol Thiocarbonates with Methyl Iodide. Synthesis of 6-Deoxy Sugars. J. Chem. Soc., Perkin Trans. 1 1975, 1773-1776.
73. Simmons, H. E.; Cairns, T. L.; Vladuchick, S. A.; Hoiness, C. M. Cyclopropanes from Unsaturated Compounds, Methylene Iodide, and Zinc-Copper Couple. Org. React. 1973, 20, 1-131.
74. 2.
75. Bond, F. T.; Cornelia, R. H. Reactions of Dihalocarbenes with Ring B Steroid Olefins. Chem. Commun. 1968, 19, 1189-1190.
76. Ireland, R. E.; Haebich, D.; Norbeck, D. W. Convergent Synthesis of Polyether Ionophore Antibiotics: The Synthesis of the Monensin Spiroketal. J. Am. Chem. Soc. 1985, 107, 3271-3278.
77. Binkley, R. W.; Hehemann, D. G. A Light-Initiated Process for Rapid Debenzylation of Carbohydrates. J. Org. Chem. 1990, 55, 378-380.
78. Chlorosulfate 82 is surprisingly stable. In THF/water (1:1) at 23°C after 1 h, it was only 10% hydrolyzed to the C1 alcohol. However, addition of excess primary amine to a THF/water solution of 82 caused rapid hydrolysis (complete in less than 5 min).
79. Treatment of 82 with diisopropylamine did not yield desired product, and tert-butylamine yielded just a trace of product. The product in these reactions was alcohol 81. Since the starting amines were anhydrous (distilled from BaO), 81 was probably formed nonhydrolytically, such as by N-chlorination and fragmentation of the resultant sulfite (Buncel, E.; Raoult, A.; Wiltshire, J. F. Bond-Scission Processes in Sulfur Compounds. VII. Alkyl-oxygen Scission in the Neutral and Alkaline Methanolysis of Methyl p-Nitrophenyl Sulfate. J. Am. Chem. Soc. 1973, 95, 799-802.
80. Buncel, E.; Raoult, A. Reaction of Phenyl Chlorosulfate with Anions. Possible Displacement at Chlorine. J. Chem. Soc., Chem. Commun. 1973, 210-211).
81. (a) Kwart, H.; Khan, A. A. Copper-Catalyzed Decomposition of Benzenesulfonyl Azide in Hydroxylic Media. J. Am. Chem. Soc. 1967, 89, 1950-1951.
82. Cram, D. J.; Day, J.; Rayner, D. R.; Von Schriltz, D. M.; Duchamp, D. J.; Garwood, D. C. Stereochemistry of Sulfur Compounds. I. Stereochemical Reaction Cycles involving an Open Chain Sulfoxide, Sulfimide, and Sulfoximide. Ibid. 1970, 92, 7369-7384.
83. Johnson, C. R.; Lavergne, O. Preparation of Free Sulfoximines by Treatment of N-Tosylsulfoximines with Sodium Anthracenide. J. Org. Chem. 1989, 54, 986-988.
84. (b) Herranz, E.; Sharpless, K. B. Osmium-Catalyzed Vicinal Oxyamination of Olefins by N-Chloro-N-metallocarbamates. J. Org. Chem. 1980, 45, 2710-2713.
85. (b) Sharpless, K. B.; Singer, S. P. 1,2-Diamination of 1,3-Dienes by Imido Selenium Compounds. Ibid. 1976, 41, 2504-2506.
86. 49b and used immediately without isolation.
87. (b) Borovikova, G. S.; Levchenko, E. S.; Borovik, E. I. Reaction of Sulfonic and Carboxylic Acid N-Haloamides with Sulfur and Sulfur Dichloride. Zh. Org. Khim. 1979, 15, 2485-2490.
88. The stereochemistry at sulfur in 90a, 91a, and 93a is tentative because it could not be assigned by NOE experiments. Since ring formation for 90a and 93a was conducted between 5°C and ambient temperature, it is presumed that the strongly biased stereoselectivity was in favor of the exo isomer, as obseved in the synthesis of 87a/b from diol 28 and 88a/b from diol 40.
89. (a) Kim, B. M.; Sharpless, K. B. Cyclic Sulfates Containing Acid-Sensitive Groups and Chemoselective Hydrolysis of Sulfate Esters. Tetrahedron Lett. 1989, 30, 655-658.
90. 4
91. Beels, C. M. D.; Coleman, M. J.; Taylor, R. J. K. The Direct Conversion of 1,2-Cydic Sulfates into Alkenes. Synlett 1990, 479-480.
92. 49b
93. Greco, M. N.; Maryanoff, B. E. Highly Stereoselective Synthesis of Substituted Hydrindanes Related to the Antiepileptic Drug Topiramate. Tetrahedron Lett. 1992, 33, 5009-5012.
94. Up to this point in the paper, all compounds reported have been single enantiomers with the D configuration. All of the hydrindane derivatives, 95-104, are racemic.
95. VanRheenen, V.; Kelly, R. C.; Cha, D. Y. An Improved Catalytic Osmium Tetroxide Oxidation of Olefins to cis-1,2-Glycols using Tertiary Amine Oxides as the Oxidant. Tetrahedron Lett. 1976, 1973-1976.
96. Tewson, T. J.; Soderlind, M. 1-Propenyl-4, 6-O-benzylidene-β-D-mannopyranoside-2,3-cyclic Sulfate: A Substrate for the Synthesis of [F-18] 2-Deoxy-2-fluoro-D-glucose. J. Carbohydr. Chem. 1985, 4, 529-543.
97. McComsey, D. F.; Maryanoff, B. E. Improved Synthesis of Pseudo-β-D-fructopyranose, a Carbocyclic Monosaccharide, from (-)-Quinic Acid. J. Org. Chem. 1994, 59, 2652-2654.
98. Chen, C.; Whistler, R. L. Synthesis of L-Fructose. Carbohydr. Res. 1988, 175, 265-271.
99. Swinyard, E. A.; Brown, W. C.; Goodman, L. S. Comparative Assays of Antiepileptic Drugs in Mice and Rats. J. Pharmacol. Exp. Ther. 1952, 106, 319-330.
100. Hansen, C.; Bjöerkroth, J. P.; Leo, A. Hydrophobicity and Central Nervous System Agents: On the Principle of Minimal Hydrophobicity in Drug Design. J. Pharm. Sci. 1987, 76, 663-687.
101. 2 (-1.29) provided the methyl correction factor of 1.05] and then adding this value to the experimental log P for 2: clogP (corr) = 0.42 + 1.05 = 1.47.
102. Dunham, N. W.; Miya, T. S. A Note on a Simple Apparatus for Detecting Neurological Deficit in Rats and Mice. J. Am. Pharm. Assoc., Sci. Ed. 1957, 46, 208-209.
103. (a) Dodgson S. The Carbonic Anhydrases: Overview of Their Importance in Cellular Physiology and in Molecular Genetics. The Carbonic Anhydrases: Cellular Physiology and Molecular Genetics; Dodgson, S. J., Tashian, R. E., Gros, G., Carter, N. D., Eds.; Plenum Press: New York, 1991.
104. (b) Fernley, R. T. Non-Cytoplasmic Carbonic Anhydrases. Trends Biochem. Sci. 1988, 13, 356-359.
105. (a) Baldwin, J. J.; Ponticello, G. S.; Anderson, P. A.; Christy, M. E.; Murcko, M. A.; Randall, W. C.; Schwam, H.; Sugrue, M. F.; Springer, J. P.; Gautheron, P.; Grove, J.; Mallorga, P.; Viader, M.-P.; McKeever, B. M.; Navia, M. A. Thienothiopyran-2-sulfonamides: Novel Topically Active Carbonic Anhydrase Inhibitors for the Treatment of Glaucoma. J. Med. Chem. 1989, 32, 2510-2513.
106. (b) Koike, T.; Kimura, E.; Nakamura, I.; Hashimoto, Y.; Shiro, M. The First Anionic Sulfonamide-Binding Zinc(II) Complexes with a Macrocyclic Triamine: Chemical Verification of the Sulfonamide Inhibition of Carbonic Anhydrase. J. Am. Chem. Soc. 1992, 114, 7338-7345.
107. (c) Vedani, A.; Huhta, D. W.; Jacober, S. P. Metal Coordination, H-Bond Network Formation, and Protein-Solvent Interactions in Native and Complexed Human Carbonic Anhydrase I: A Molecular Mechanics Study. J. Am. Chem. Soc. 1989, 111, 4075-4081.
108. (d) Dugad, L. B.; Cooley, C. R.; Gerig, J. T. NMR Studies of Carbonic Anhydrase-Fluorinated Benzenesulfonamide Complexes. Biochemistry 1989, 28, 3955-3960.
109. (e) Vidgren, J.; Liljas, A.; Walker, N. P. C. Refined Structure of the Acetazolamide Complex of Human Carbonic Anhydrase II at 1.9 Å. Int. J. Biol. Macromol. 1990, 12, 342-344.
110. For a review of this program, see: Kupferberg, H. J.; Swinyard, E. A.; Gladding, G. D. ADD Program of NINCDS: Early Pharmacological Evaluation of New Antiepileptic Drugs. Adv. Epileptol. 1980 (publ. 1981), 12, 13-18.
111. Edmonds, H. L., Jr.; Jiang, Y. D.; Zhang, P. Y.; Shank, R. P. Anticonvulsant Activity of Topiramate and Phenytoin in a Rat Model of Ischemia-induced Epilepsy. Life Sci. 1996, 59, PL127-PL131.
112. Nakamura, J.; Tamara, S.; Kanda, T.; Ishii, A.; Ishihara, K.; Serikawa, T.; Yamada, J.; Sasa, M. Inhibition by Topiramate of Seizures in Spontaneously Epileptic Rats and DBA/2 Mice. Eur. J. Pharmacol. 1994, 254, 83-89.
113. Wauquier, A.; Zhou, S. Topiramate: A Potent Anticonvulsant in the Amygdala-Kindled Rat. Epilepsy Res. 1996, 24, 73-77.
114. (a) Sachdeo, R. C.; Reife, R. A.; Lim, P.; Pledger, G. Topiramate Monotherapy for Partial Onset Seizures. Epilepsia 1997, 38, 294-300.
115. (b) Sharief, M.; Viteri, C.; Ben-Menachem, E.; Weber, M.; Reife, R.; Pledger, G.; Karim, R. Double-blind, Placebo-controlled Study of Topiramate in Patients with Refractory Partial Epilepsy. Epilepsy Res. 1996, 25, 217-224.
116. (c) Tassinari, C. A.; Michelucci, R.; Chauvel, P.; Chodkiewicz, J.; Shorvon, S.; Henriksen, O.; Dam, M.; Reife, R.; Pledger, G.; Karim, R. Double-blind, Placebo-controlled Trial of Topiramate (600 mg Daily) for the Treatment of Refractory Partial Epilepsy. Epilepsia 1996, 37, 763-768.
117. (d) Ben-Menachem, E.; Henriksen, O.; Dam, M.; Mikkelsen, M.; Schmidt, D.; Reid, S.; Reife, R.; Kramer, L.; Pledger, G.; Karim, R. Double-blind, Placebo-controlled Trial of Topiramate as Add-on Therapy in Patients with Refractory Partial Seizures. Epilepsia 1996, 37, 539-543.
118. (a) Kanda, T.; Kurokawa, M.; Tamura, S.; Nakamura, J.; Ishii, A.; Kuwana, Y.; Serikawa, T.; Yamada, J.; Ishihara, K.; Sasa, M. Topiramate Reduces Abnormally High Extracellular Levels of Glutamate and Aspartate in the Hippocampus of Spontaneously Epileptic Rats (SER). Life Sci. 1996, 59, 1607-1616.
119. (b) White, H. S.; Brown, S. D.; Skeen, G. A.; Twyman, R. E. The Investigational Anticonvulsant Topiramate Potentiates GABA-Evoked Currents in Mouse Cortical Neurons. Epilepsia 1995, 36 (S4), 34.
120. (c) White, H. S.; Brown, S. D.; Woodhead, J. H.; Skeen, G. A.; Wolf, H. H. Topiramate Enhances GABA-Mediated Chloride Flux and GABA-Evoked Chloride Currents in Murine Brain Neurons and Increases Seizure Threshold. Epilepsy Res. 1997, 28, 167-179.
121. (d) Severt, L.; Gibbs, J. W., III.; Coulter, D. A.; Sombati, S.; DeLorenzo, R. J. Topiramate Selectively Blocks Kainate Currents in Cultured Hippocampal Neurons. Epilepsia 1995, 36 (S4), 38.
122. 2+-Induced Seizure Discharges in Cultured Hippocapmal Neurons. Epilepsia 1995, 36 (S4), 38.
123. + Currents in Rat Cerebellar Granule Cells. Neurosci. Lett. 1997, 231, 123-126.
124. For conformational analysis of an analogous system, see: Köll, P.; Kopf, J. Derivatives of Fructose in Unusual Conformation: Crystal and Molecular Structure of 1,4,5-Tri-O-acetyl-2,3-O-isopropylidene-β-D-fructopyranose. Chem. Ber. 1976, 109, 3346-3357.
125. (a) Maeda, T.; Tori, K.; Saton, S.; Tokuyama, K. Sorboses. XVI. Conformational Studies of Acetonated α-L-Sorbo- and β-D-Fructopyranoses by Means of Proton Magnetic Resonance Spectroscopy. Bull. Chem. Soc. Jpn. 1969, 42, 2635-2647.
126. (b) Brady, R. F., Jr. Cyclic Acetals of Ketoses. Adv. Carbohydr. Chem. Biochem. 1971, 26, 197-278.
127. 3CN.
128. Details for the crystallography are given in the Supporting Information.
129. See the paragraph at the end of this paper regarding Supporting Information.
130. 29 and the details for 21a will be published separately.
131. Dauben, W. G.; McFarland, J. W.; Rogan, J. B. Preparation of cis-Hexahydroindane-8-carboxylic Acid. J. Org. Chem. 1961, 26, 297-300.
132. We thank Prof. Wendy Cammer (Albert Einstein College of Medicine, Bronx, NY) for communicating this method to us prior to publication.