Claims
- 1. An amino acid halide comprising a 5-member heteroaromatic ring, the amino acid halide having a formula (4), (5) or (6):
- 2. The amino acid halide of claim 1 having formula (5), wherein when X4 is S and X1 is N, R3 is substituted or unsubstituted C2-C10 alkyl.
- 3. The amino acid halide of claim 1 having formula (4), wherein when X1 is N and X3 is CH, R2 is hydrogen or substituted or unsubstituted C2-C10 alkyl.
- 4. The amino acid halide of claim 1 having formula (6), wherein when X3 is N and X2 is S, R3 is substituted or unsubstituted C1-C10 alkyl.
- 5. The amino acid halide of claim 1 having the formula:
- 6. The amino acid halide of claim 5 wherein Z is t-butoxycarbonyl.
- 7. The amino acid halide of claim 5 wherein Z is 9-fluoroenylmethoxycarbonyl.
- 8. The amino acid halide of claim 1 having the formula:
- 9. The amino acid halide of claim 8 wherein Z is t-butoxycarbonyl.
- 10. The amino acid halide of claim 8 wherein Z is 9-fluoroenylmethoxycarbonyl.
- 11. The amino acid halide of claim 1 wherein the heteroaromatic ring is selected from pyrrole, imidazole, furan, pyrazole, thiophene, oxazole, thiazole and 1,2,4-triazole.
- 12. The amino acid halide of claim 1 having a formula (7A), (7B), (9A) or (9B):
- 13. The amino acid halide of claim 12 wherein Z is a protecting group and Z′ is hydrogen.
- 14. The amino acid halide of claim 13 wherein Z is t-butoxycarbonyl or 9-fluoroenylmethoxy carbonyl.
- 15. The amino acid halide of claim 14 wherein Q is Cl.
- 16. The amino acid halide of claim 15 having formula (7A) or (7B).
- 17. The amino acid halide of claim 16 wherein X1 is CH and R2 is H or CH3.
- 18. The amino acid halide of claim 15 having formula (9A) or (9B).
- 19. The amino acid halide of claim 18 wherein X2 is NH or NCH3 and R3 is H or CH3.
- 20. The amino acid halide of claim 18 wherein X2 is O.
- 21. An amino acid halide oligomer comprising a 5-member heteroaromatic or a 6-member aromatic or heteroaromatic ring, the oligomer having a formula (10), (11) or (12):
- 22. The oligomer of claim 21 wherein L is independently selected from substituted or unsubstituted ethylene, substituted or unsubstituted propylene, substituted or unsubstituted heteroarylene, and substituted or unsubstituted arylene.
- 23. The amino acid halide oligomer of claim 21 wherein a is an integer in the range of about 1 to about 10.
- 24. The amino acid halide oligomer of claim 23 wherein a is an integer in the range of about 2 to about 8.
- 25. The amino acid halide oligomer of claim 23 wherein a is an integer in the range of about 3 to about 5.
- 26. The amino acid halide oligomer of claim 23 having formula (11) wherein X4 is O and X1 is N or CH.
- 27. The amino acid halide oligomer of claim 23 having formula (11) wherein X4 is S and X, is N or CH.
- 28. The amino acid halide oligomer of claim 23 having formula (12) wherein X2 is NR1 and X3 is CH.
- 29. The amino acid halide oligomer of claim 23 having formula (10) wherein X3 is CH and X1 is N or CH.
- 30. The amino acid halide oligomer of claim 23 having formula (10) wherein X3 is N and X1 is N or CH.
- 31. The amino acid halide oligomer of claim 21 comprising a 5-member heteroaromatic ring and having a formula (16A), (16B), (18A) or (18B):
- 32. The amino acid halide oligomer of claim 31 having formula (16A) or (16B).
- 33. The amino acid halide oligomer of claim 31 having formula (18A) or (18B).
- 34. The amino acid halide oligomer of claim 21 comprising a 6-membered aromatic or heteroaromatic ring.
- 35. The amino acid halide of claim 34 wherein the ring is selected from benzene, pyridine, pyrimidine, pyridazine, pyrazine and 1,2,4-triazine.
- 36. A process for preparing an amino acid halide, P—COQ, wherein P represents a substituted or unsubstituted, 5-member heteroaromatic or 6-member aromatic or heteroaromatic ring which has a protected amino group bound thereto, CO represents a carbonyl group bound to the ring, and Q represents a halo group bound to the carbonyl carbon, the process comprising contacting an immobilized α-haloenamine and a carboxylic acid, P—CO2H, that corresponds structurally to the amino acid halide except that Q is hydroxy instead of halo.
- 37. The process of claim 36 wherein the amino acid halide has a formula (1), (2) or (3):
- 38. The process of claim 37 wherein the amino acid halide has the formula (1), and wherein X3 is CH or N and X1 is CH or N.
- 39. The process of claim 37 wherein the amino acid halide has the formula (3), and wherein X2 is NH and X3 is N or CH.
- 40. The process of claim 37 wherein the amino acid halide has the formula (2), wherein X1 is CH or N and X4 is O or S.
- 41. The process of claim 36 wherein the α-haloenamine has the formula:
- 42. The process of claim 36 wherein the resulting amino acid halide has a purity within a range of at least about 95 wt % to about 99.9 wt %.
- 43. The process of claim 36 wherein a yield of the resulting amino acid halide ranges from at least about 90% to about 99%.
- 44. The process of claim 36 wherein the amino acid halide and the α-haloenamine are contacted in a reaction zone for a duration of less than about 10 minutes.
- 45. A process for preparing an amino acid halide, the amino acid halide comprising a 5-member heteroaromatic or 6-member aromatic or heteroaromatic ring and having a formula (1), (2) or (3):
- 46. The process of claim 45 wherein the resulting amino acid halide has a purity within a range of at least about 95 wt % to about 99.9 wt %.
- 47. The process of claim 45 wherein a yield of the resulting amino acid halide ranges from at least about 90% to about 99%.
- 48. The process of claim 45 wherein the amino acid halide and the α-haloenamine are contacted in a reaction zone for a duration of less than about 10 minutes.
- 49. The process of claim 45 wherein a is 0, the amino acid halide comprising a 5-member heteroaromatic ring and having a formula (4), (5) or (6):
- 50. The process of claim 45 wherein the α-haloenamine has the formula:
- 51. A process for preparing a polyamide oligomer or polymer, the process comprising:
(a) forming a population of amino-protected, amino acid halide building block units possessing a 5-member heteroaromatic or 6-member aromatic or heteroaromatic moiety therein, said units having a formula P—COQ, wherein P represents the aromatic or heteroaromatic moiety to which is bound a protected amino group, CO represents a carbonyl group bound to the aromatic or heteroaromatic moiety, and Q represents a halo group bound to the carbonyl carbon, the units being formed by contacting an α-haloenamine and a carboxylic acid, P—CO2H, that corresponds structurally to the amino acid halide except that Q is hydroxy instead of halo; (b) combining a member of the population of amino-protected, amino acid halide building block units with a moiety comprising an unprotected amino functionality to form a reaction product possessing an amide linkage and a protected amino functionality; (c) deprotecting the amino group of the reaction product; and, (d) repeating steps (b) and (c) at least once, wherein the deprotected reaction product formed in step (c) is used as the moiety comprising an unprotected amino functionality in a subsequent step (b).
- 52. The process of claim 51 wherein said acid halide has a purity within a range of at least about 95wt % to about 99.9 wt %.
- 53. The process of claim 51 wherein the moiety comprising an unprotected amino functionality is supported.
- 54. The process of claim 51 wherein the amino group nitrogen is protected as a carbamate.
- 55. The process of claim 51 wherein a ratio of equivalents of the amino-protected, amino acid halide building block units to the moiety comprising an unprotected amino functionality is within a range of about 1:1 to less than about 3:1.
- 56. The process of claim 51 wherein the yield of said reaction product is with a range of about 90% to about 99%.
- 57. The process of claim 51 wherein a member of the population of amino-protected, amino acid halide building block units is combined with a moiety comprising an unprotected amino functionality to form a reaction product for a duration of less than about 10 minutes.
- 58. The process of claim 51 wherein the α-haloenamine has the formula:
- 59. The process of claim 51 wherein the amino acid halide building block has a formula (1), (2) or (3):
- 60. The process of claim 59 wherein a is 0.
- 61. The process of claim 60 wherein Q is Cl.
- 62. The process of claim 61 wherein Z is t-butoxycarbonyl.
- 63. The process of claim 61 wherein Z is 9-fluoroenylmethoxycarbonyl.
- 64. The process of claim 59 wherein a is an integer in the range of about 1 to about 10.
- 65. The process of claim 64 wherein a is an integer in the range of about 2 to about 8.
- 66. The process of claim 65 wherein Q is Cl.
- 67. The process of claim 66 wherein Z is t-butoxycarbonyl.
- 68. The process of claim 59 wherein steps (b), (c) and (d) are automated.
- 69. A process for preparing a polyamide oligomer or polymer, the process comprising:
(a) forming a population of amino-protected, amino acid halide building block units comprising a 5-member heteroaromatic ring and having a formula (4), (5) or (6): 43 wherein:
Q is Cl or Br; Z and Z′ are independently hydrogen or an amine protecting group which may be the same or different, provided that at least one of Z and Z′, together with the nitrogen atom to which they are attached, form a carbamate moiety; X, is N or CR1; X2 is O, S or NR1; X3 is N or CR4; X4 is O or S; R1 is independently selected from hydrogen and substituted or unsubstituted alkyl; R2 is independently selected from hydrogen, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C2-C10 alkenyl, or substituted or unsubstituted C2-C10 alkynyl; R3 is independently selected from hydrogen, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C2-C10 alkenyl, substituted or unsubstituted C2-C10 alkynyl or halo; and, R4 is independently selected from hydrogen, hydroxy or alkoxy; (b) combining a member of the population of amino-protected, amino acid halide building block units with a moiety comprising an unprotected amino functionality to form a reaction product possessing an amide linkage and a protected amino functionality; (c) deprotecting the amino group of the reaction product; and, (d) repeating steps (b) and (c) at least once, wherein the deprotected reaction product formed in step (c) is used as the moiety comprising an unprotected amino functionality in a subsequent step (b).
- 70. The process of claim 69 wherein said amino acid halide building blocks have a formula (7A), (7B), (9A) or (9B):
- 71. The process of claim 69 wherein the amino acid halide has a purity within a range of at least about 95 wt % to about 99.9 wt %.
- 72. The process of claim 69 wherein a ratio of equivalents of the amino-protected, amino acid halide building block units to the moiety comprising an unprotected amino functionality is within a range of about 1:1 to less than about 3:1.
- 73. The process of claim 69 wherein steps (b), (c) and (d) are automated.
- 74. The process of claim 69 wherein the yield of said reaction product is with a range of about 90% to about 99%.
- 75. The process of claim 69 wherein a member of the population of amino-protected, amino acid halide building block units is combined with a moiety comprising an unprotected amino functionality to form a reaction product for a duration of less than about 10 minutes.
REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority from U.S. Provisional Application Serial No. 60/316,151, filed on Aug. 30, 2001 and U.S. application Ser. No. 10/061,617, filed on Feb. 1, 2002, both of which are incorporated in their entireties herein by reference.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60316151 |
Aug 2001 |
US |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
10061617 |
Feb 2002 |
US |
Child |
10232244 |
Aug 2002 |
US |