Claims
- 1. A compound having the structure:
- 2. The compound of claim 1 having the structure:
- 3. The compound of claim 1 wherein the protein is bovine serum albumin or KLH.
- 4. A compound having the structure:
- 5. The compound of claim 4 wherein r is 1.
- 6. A method of preparing a trisaccharide iodosulfonamide having the structure:
- 7. The method of claim 6 wherein the disaccharide glycal having the structure:
- 8. The method of claim 7 wherein the silylating agent in step (a) is triphenylsilyl chloride.
- 9. The method of claim 7 wherein the alkylating step is effected in the presence of an ionizing salt, and the ionizing salt is AgClO4.
- 10. The method of claim 7 wherein the conditions of the deprotecting step comprise a base.
- 11. The method of claim 10 wherein the base is potassium carbonate.
- 12. The method of claim 6 wherein the conditions of the coupling comprise an acid.
- 13. The method of claim 6 wherein the acid is a Lewis acid.
- 14. The method of claim 13 wherein the Lewis acid is zinc dichloride.
- 15. The method of claim 7 wherein the protecting agent is TBSOTf.
- 16. The method of claim 6 wherein the iodosulfonamidating agent of step (b) comprises I(coll)2ClO4 and and PhSO2NH2.
- 17. A method of preparing a disaccharide stannane having the structure:
- 18. The method of claim 17 wherein the conditions of the deprotecting step comprise a fluoride salt.
- 19. The method of claim 18 wherein the fluoride salt is a tetraalkylammonium fluoride.
- 20. The method of claim 19 wherein the tetraalkylammonium fluoride salt is tetra-n-butylammonium fluoride.
- 21. The method of claim 17 wherein the conditions of the reprotecting step comprise 2-chloro-1-methylpyridinium iodide.
- 22. The method of claim 17 wherein R is n-Bu.
- 23. A method of preparing a disaccharide ethylthioglycoside having the structure:
- 24. The method of claim 23 wherein the disaccharide glucal is prepared by a process which comprises:
(a) alkylating a protected glucal having the structure: 83with a fucosyl fluoride having the structure: 84under suitable conditions to form the disaccharide glucal.
- 25. The method of claim 24 wherein the conditions of the alkylating step comprise an ionizing salt.
- 26. The method of claim 25 wherein the ionizing salt is AgClO4.
- 27. The method of claim 23 wherein the protecting agent is PMBCl.
- 28. The method of claim 23 wherein the iodosulfonamidating agent in step (b)(ii) comprises I(coll)2ClO4 and PhSO2NH2.
- 29. The method of claim 23 wherein the conditions of the treating step comprise a base.
- 30. The method of claim 29 wherein the base is LHMDS.
- 31. A method of preparing an N3 allyl glycoside having the structure:
- 32. The method of claim 31 wherein the protected N3 glycal is prepared by a process which comprises coupling an ethylthioglycoside having the structure:
- 33. The method of claim 32 wherein the alkylating agent is MeOTf.
- 34. The method of claim 32 wherein the conditions of the desilylating step comprise a fluoride salt.
- 35. The method of claim 34 wherein the fluoride salt is a tetraalkylammonium fluoride.
- 36. The method of claim 35 wherein the tetraalkylammonium fluoride is tetra-n-butylammonium fluoride.
- 37. The method of claim 31 wherein the catalyst in the treating step is 2-N,N-dimethylaminopyridine.
- 38. The method of claim 31 wherein the oxygen transfer agent is 3,3-dimethyidioxirane.
- 39. A method of preparing a heptasaccharide glycal diacetate intermediate having the structure:
- 40. The method of claim 39 wherein the heptasaccharide glycal is prepared by a process which comprises:
(a) (i) reacting a trisaccharide iodosulfonamide having the structure: 91with a disaccharide stannane having the structure: 92under suitable conditions; and (ii) deprotecting under suitable conditions to form a pentasaccharide glycal having the structure: 93and (b) coupling the pentasaccharide glycal formed in step (a) with an ethylthioglycoside having the structure: 94under suitable conditions to form the heptasaccharide glycal.
- 41. The method of claim 40 wherein the conditions of the reacting step comprise an ionizing agent.
- 42. The method of claim 41 wherein the ionizing agent is AgBF4.
- 43. A method of preparing a protected disaccharide having the structure:
- 44. The method of claim 43 wherein the galactal carbonate is prepared by a process which comprises:
(a) protecting a galactal having the structure: 99with an alkylating agent under suitable conditions to form a first protected galactal; and (b) treating the first protected galactal formed in step (a) with a carbonate-forming reagent under conditions suitable to form the galactal carbonate.
- 45. The method of claim 44 wherein the carbonate-forming reagent is (Im)2CO/DMAP.
- 46. The method of claim 43 wherein the doubly protected galactal is prepared by a process which comprises:
(a) protecting a second galactal having the structure: 100with an alkylating agent under conditions suitable to form a second protected galactal; and (b) protecting the second protected galactal formed in step (a) with an alkylating agent which may be the same or different from that of step (a) under conditions suitable to form the doubly protected galactal.
- 47. The method of claim 46 wherein each alkylating agent is independently an alkyl, arylalkyl, trialkylsilyl, aryldialkylsilyl, diarylalkylsilyl or triarylsilyl halide or triflate.
- 48. The method of claim 47 wherein the alkylating agent is benzyl bromide.
- 49. The method of claim 47 wherein the alkylating agent is TES-Cl.
- 50. The method of claim 43 wherein the oxygen transfer agent is DMDO.
- 51. The method of claim 43 wherein the conditions of the coupling step comprise ZnCl2 in THF.
- 52. The method of claim 43 wherein the conditions of the saponifying step comprise K2CO3 in methanol.
- 53. A method of preparing an ethylthioglycoside having the structure:
- 54. The method of claim 53 wherein the protected disaccharide carbonate is prepared by a process which comprises alkylating a disaccharide carbonate having the structure:
- 55. The method of claim 54 wherein the alkylating agent is an alkyl, arylalkyl, trialkylsilyl, aryldialkylsilyl, diarylalkylsilyl or triarylsilyl halide or triflate.
- 56. The method of claim 55 wherein the alkylating agent is TES-Cl.
- 57. The method of claim 53 wherein the iodosulfonamidating agent is I(coll)2ClO4 and PhSO2NH2.
- 58. A method of preparing an ethylthioglycoside having the structure:
- 59. The method of claim 58 wherein the conditions of the acylating step comprise acetic anhydride/pyridine.
- 60. The method of claim 58 wherein the iodosulfonamidating agent is I(coll)2ClO4 and PhSO2NH2.
- 61. A method of preparing a protected hexasaccharide having the structure:
- 62. The method of claim 61 wherein the protected tetrasaccharide is prepared by a process which comprises:
(a) coupling an ethythioglycoside having the structure: 112with a protected disaccharide having the structure: 113under suitable conditions to form a protected tetrasaccharide carbonate; and (b) saponifying the protected tetrasaccharide carbonate formed in step (a) under suitable conditions to form the protected tetrasaccharide.
- 63. The method of claim 62 wherein the conditions of the coupling step comprise MeOTf/MS.
- 64. The method of claim 62 wherein the conditions of the saponifying step comprise K2CO3 in methanol.
- 65. A method of preparing a protected nonasaccharide having the structure:
- 66. The method of claim 65 wherein the conditions of the deprotecting step comprise a fluoride salt.
- 67. The method of claim 66 wherein the fluoride salt is a tetraalkylammonium fluoride.
- 68. The method of claim 67 wherein the fluoride salt is TBAF.
- 69. The method of claim 65 wherein the organometallic reagent is Sn(OTf)2/DTBP.
- 70. A method of preparing a protected nonasaccharide ceramide having the structure:
- 71. The method of claim 70 wherein the oxygen transfer agent is DMDO.
- 72. The method of claim 70 wherein the conditions of the coupling step comprise ZnCl2.
- 73. The method of claim 70 wherein the azide intermediate is reductively acylated in step (c) in the presence of Lindlar's catalyst.
- 74. The method of claim 70 wherein conditions of the saponifying step comprise MeONa in methanol.
- 75. A method of inducing antibodies in a subject, wherein the antibodies are capable of specifically binding with epithelial tumor cells, which comprises administering to the subject an amount of a compound which contains a determinant having a structure selected from the group consisting of:
- 76. The method of claim 75 wherein the compound is bound to a suitable carrier protein, said compound being bound either directly or by a cross-linker selected from the group consisting of a succinimide and an M2 linker.
- 77. The method of claim 75 wherein the compound contains a KH-1 or N3 epitope.
- 78. The method of claim 76 wherein the carrier protein is bovine serum albumin, polylysine or KLH.
- 79. The method of claim 76 wherein the compound is a KH-1 or N3 epitope.
- 80. The method of claim 75 which further comprises co-administering an immunological adjuvant.
- 81. The method of claim 80 wherein the adjuvant is bacteria or liposomes.
- 82. The method of claim 80 wherein the adjuvant is Salmonella minnesota cells, bacille Calmette-Guerin or QS21.
- 83. The method of claim 75 wherein the epithelial tumor cells are gastrointestinal tumor cells.
- 84. The method of claim 83 wherein the gastrointestinal tumor cells are are colon tumor cells.
- 85. The method of claim 75 wherein the epithelial tumor cells are lung tumor cells.
- 86. The method of claim 75 wherein the epithelial tumor cells are prostate tumor cells.
- 87. A method of treating a subject suffering from an epithelial cell cancer, which comprises administering to the subject an amount of a compound which contains a determinant having a structure selected from the group consisting of:
- 88. The method of claim 87 wherein the compound is bound to a suitable carrier protein, said compound being bound either directly or by a cross-linker selected from the group consisting of a succinimide and an M2 linker.
- 89. The method of claim 88 wherein the carrier protein is bovine serum albumin, polylysine or KLH.
- 90. The method of claim 87 or 89 wherein the compound is contains a KH-1 or N3 epitope.
- 91. The method of claim 87 or 90 which further comprises co-administering an immunological adjuvant.
- 92. The method of claim 91 wherein the adjuvant is bacteria or liposomes.
- 93. The method of claim 91 wherein the adjuvant is Salmonella minnesota cells, bacille Calmette-Guerin or QS21.
- 94. A method of preventing recurrence of an epithelial cell cancer in a subject which comprises vaccinating the subject with a compound which contains a determinant having the structure:
(a) 122which amount is effective to prevent recurrence of an epithelial cell cancer.
- 95. The method of claim 94 wherein the compound is bound to a suitable carrier protein.
- 96. The method of claim 94 wherein the carrier protein is bovine serum albumin, polylysine or KLH.
- 97. The method of claim 94 which further comprises co-administering an immunological adjuvant.
- 98. The method of claim 97 wherein the adjuvant is bacteria or liposomes.
- 99. The method of claim 97 wherein the adjuvant is Salmonella minnesota cells, bacille Calmette-Guerin or QS21.
- 100. The method of claim 75, 87 or 94 wherein the compound is selected from the group consisting of:
- 101. A composition comprising a compound which contains a determinant having a structure selected from the group consisting of:
- 102. The composition of claim 101 wherein the compound is bound to a suitable carrier protein, said compound being bound either directly or by a cross-linker selected from the group consisting of a succinimide and an M2 linker.
- 103. The composition of claim 102 wherein the carrier protein is bovine serum albumin, polylysine or KLH.
- 104. The composition of claim 101 or 103 wherein the compound contains a KH-1 or N3 epitope.
- 105. The composition of claim 101 wherein the immunological adjuvant is bacteria or liposomes.
- 106. The composition of claim 105 wherein the adjuvant is Salmonella minnesota cells, bacille Calmette-Guerin or QS21.
- 107. The composition of claim 106 wherein the compound has the structure:
(a) 126wherein R is H, substituted or unsubstituted alkyl, aryl or allyl, or an amino acyl moiety, an amino acyl residue of a peptide, an amino acyl residue of a protein, which amino acyl moiety or residue bears an ω-amino group or an ω-(C═O)— group, which group is linked to O via a polymethylene chain having the structure —(CH2)s—, where s is an integer between about 1 and about 9, or a moiety having the structure: 127and wherein r, m and n are independently 0, 1, 2 or 3.
Parent Case Info
[0001] This application is based on U.S. Provisional Application Serial No. 60/034,950, filed Jan. 13, 1997, the contents of which are hereby incorporated by reference into this application.
Government Interests
[0002] This invention was made with government support under grants CA-28824-18, GM-15240-02, GM-16291-01, HL-25848-14 and AI-16943 from the National Institutes of Health. Accordingly, the U.S. Government has certain rights in the invention.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60034950 |
Jan 1997 |
US |
Divisions (1)
|
Number |
Date |
Country |
Parent |
09042280 |
Jan 1998 |
US |
Child |
09833327 |
Apr 2001 |
US |