Granted Patent B2

US 6,965,034 · App. 10/329,090 · Granted Nov 15, 2005

Assignee: Sloan-Kettering Institute for Cancer Research

Abstract

Claims (123)

1. A process of making a desoxyepothilone comprising:

(a) reacting a desoxyepothilone precursor having the structure:

 with a macrolactonization reagent, wherein the macrolactonization reagent is selected from the group consisting of acetic anhydride, pentafluorophenol, 2,4-dichlorobenzoyl chloride, and 2.4,6-trichlorobenzoyl chloride, to generate a desoxyepothilone having the structure:

wherein R, R 0 and R′ are independently H, linear or branched chain alkyl, optionally substituted by hydroxy, OR 3 , alkoxy, carboxy, carboxaldehyde, linear or branched alkyl or cyclic acetal, fluorine, NR 1 R 2 , N-hydroximino, or N-alkoxyimino, wherein R 1 and R 2 are independently H, phenyl, benzyl, linear or branched chain alkyl; and R 3 is hydrogen, substituted or unsubstituted trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, or triarylsilyl;

R″ is —CY═CHX, or H, linear or branched chain alkyl, phenyl, 2-methyl-1,3-thiazol-4-yl, 2-furanyl, 3-furanyl, 4-furanyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, imidazolyl, 2-methyl-1,3-oxazol-4-yl, 3-indolyl or 6-indolyl; Y is H or linear or branched chain alkyl; and X is H, linear or branched chain alkyl, phenyl, 2-methyl-1,3-thiazol-4-yl, 2-furanyl, 3-furanyl, 4-furanyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, imidazolyl, 2-methyl-1,3-oxazol-4-yl, 3-indolyl or 6-indolyl; wherein Y is H or linear or branched chain alkyl;

R A is hydrogen or a linear or branched alkyl, substituted or unsubstituted alkoxyalkyl, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted aryloxyalkyl, trialkylsilyl, aryldialkylsilyl, diarylalkylsilyl, triarylsilyl, linear or branched acyl, substituted or unsubstituted aroyl or benzoyl;

R B is hydrogen, substituted or unsubstituted alkoxycarbonyl, t-butyloxycarbonyl, amyloxycarbonyl, (trialkylsilyl)alkyloxycarbonyl, (dialkylarylsilyl)alkoxycarbonyl, benzyl, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, a linear or branched acyl, or substituted or unsubstituted aroyl or benzoyl; and

n is 2or 3.

2. The process of claim 1 , wherein the reaction is performed in the presence of a tertiary amine selected from the group consisting of triethylamine, tri-n-propylamine, diisopropylethylamine, and diethylisopropylamine and optionally in the presence of pyridine or N,N-dimethylaminopyridine.

3. The process of claim 1 , wherein in the desoxyepothilone precursor n is 3, and R″ is —CCH 3 ═CHX, wherein X is phenyl, 1,3-thiazol-4-yl, or 1,3-oxazol-4-yl.

4. The process of claim 1 , wherein in the desoxyepothilone precursor R 0 is hydrogen and R′ is methyl.

5. The process of claim 1 , wherein in the desoxyepothilone precursor R is hydrogen; methyl; ethyl; n-propyl; n-hexyl; CO 2 Et;

CH 2 OH; CH 2 OR 3 ; (CH 2 ) 3 —OH; or (CH 2 ) 3 —OR 3 ,

wherein each occurrence of R 3 is independently hydrogen, substituted or unsubstituted trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, or triarylsilyl.

6. The process of claim 1 , wherein in the desoxyepothilone precursor

R A , R B and R 3 are each independently hydrogen; linear or branched, substituted or unsubstituted trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, or triarylsilyl; or linear or branched, substituted or unsubstituted alkoxycarbonyl.

7. The process of claim 1 , wherein in the desoxyepothilone precursor

n is 3,

R″ is —CCH 3 ═CHX, wherein X is phenyl, 1,3-thiazol-4-yl, or 1,3-oxazol-4-yl,

R 0 is hydrogen and R′ is methyl;

R is hydrogen; methyl; ethyl; n-propyl; n-hexyl; CO 2 Et;

 CH 2 OH; CH 2 OR 3 ; (CH 2 ) 3 —OH; or (CH 2 ) 3 —OR 3 ; and

wherein R A , R B and R 3 are each independently hydrogen; linear or branched, substituted or unsubstituted trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, or triarylsilyl or linear or branched, substituted or unsubstituted alkoxycarbonyl.

8. The process of claim 7 , wherein in the desoxyepothilone precursor R A , R B and R 3 are each independently hydrogen, t-butyldimethylsilyl, t-butyldiphenylsilyl, triethylsilyl or 2,2,2-trichloroethoxycarbonyl.

9. The process of claim 1 ,

wherein the step of reacting a desoxyepothilone precursor comprises macrolactonizing a desoxyepothilone precursor having the structure:

 to generate a desoxyepothilone having the structure:

wherein R, R 0 and R′ are independently H, linear or branched chain alkyl, optionally substituted by hydroxy, OR 3 , alkoxy, carboxy, carboxaldehyde, linear or branched alkyl or cyclic acetal, fluorine, NR 1 R 2 , N-hydroximino, or N-alkoxyimino, wherein R 1 and R 2 are independently H, phenyl, benzyl, linear or branched chain alkyl; and R 3 is hydrogen, substituted or unsubstituted trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, or triarylsilyl;

R A is hydrogen or a linear or branched alkyl, substituted or unsubstituted alkoxyalkyl, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted aryloxyalkyl, trialkylsilyl, aryldialkylsilyl, diarylalkylsilyl, triarylsilyl, linear or branched acyl, substituted or unsubstituted aroyl or benzoyl;

R B is hydrogen, substituted or unsubstituted alkoxycarbonyl, t-butyloxycarbonyl, amyloxycarbonyl, (trialkylsilyl)alkyloxycarbonyl, (dialkylarylsilyl)alkoxycarbonyl, benzyl, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, a linear or branched acyl, or substituted or unsubstituted aroyl or benzoyl.

10. The process of claim 9 , wherein in the desoxyepothilone precursor, R 0 is hydrogen and R′ is methyl.

11. The process of claim 9 , wherein in the desoxyepothilone precursor R is hydrogen; methyl; ethyl; n-propyl; n-hexyl; CO 2 Et;

CH 2 OH; CH 2 OR 3 ; (CH 2 ) 3 —OH; or (CH 2 ) 3 —OR 3 ,

wherein each occurrence of R 3 is hydrogen, or substituted or unsubstituted trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, or triarylsilyl.

12. A process of making a desoxyepothilone comprising:

(a) reacting a desoxyepothilone precursor having the structure:

 with a macrolactonization reagent, wherein the macrolactonization reagent is selected from the group consisting of acetic anhydride, pentafluorophenol, 2,4-dichlorobenzoyl chloride, and 2,4,6-trichlorobenzoyl chloride, to generate a desoxyepothilone having the structure:

 wherein R is hydrogen, linear or branched chain alkyl, optionally substituted by hydroxy, OR 3 , alkoxy, carboxy, carboxaldehyde, linear or branched alkyl or cyclic acetal, fluorine, NR 1 R 2 , N-hydroximino, or N-alkoxyimino, wherein R 1 and R 2 are independently H, phenyl, benzyl, linear or branched chain alkyl; and R 3 is hydrogen, substituted or unsubstituted trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, or triarylsilyl;

R A is hydrogen or a linear or branched alkyl, substituted or unsubstituted alkoxyalkyl, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted aryloxyalkyl, trialkylsilyl, aryldialkylsilyl, diarylalkylsilyl, triarylsilyl, linear or branched acyl, substituted or unsubstituted aroyl or benzoyl;

R B is hydrogen, substituted or unsubstituted alkoxycarbonyl, t-butyloxycarbonyl, amyloxycarbonyl, (trialkylsilyl)alkyloxycarbonyl, (dialkylarylsilyl)alkoxycarbonyl, benzyl, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, a linear or branched acyl, or substituted or unsubstituted aroyl or benzoyl.

13. The process of claim 12 , wherein in the desoxyepothilone precursor R A , R B and R 3 are each independently hydrogen, t-butyldimethylsilyl, t-butyldiphenylsilyl, triethylsilyl or 2,2,2-trichloroethoxycarbonyl.

14. The process of claim 12 , wherein in the desoxyepothilone precursor R is substituted or unsubstituted, linear or branched chain alkyl; R A and R B are each independently hydrogen, t-butyldimethylsilyl, t-butyldiphenylsilyl, triethylsilyl or 2,2,2-trichloroethoxycarbonyl.

15. The process of claim 12 , wherein in the desoxyepothilone precursor R is linear or branched chain alkyl, optionally substituted by hydroxy, OR 3 , fluorine, cyclic acetal, or NR 1 R 2 , wherein R 1 and R 2 are each independently H, phenyl, benzyl, or linear or branched chain alkyl; R A , R B and R 3 are each independently hydrogen, t-butyldimethylsilyl, t-butyldiphenylsilyl, triethylsilyl or 2,2,2-trichloroethoxycarbonyl.

16. The process of claim 12 , wherein in the desoxyepothilone precursor R is linear or branched chain alkyl substituted by fluorine; R A and R B are each independently hydrogen, t-butyldimethylsilyl, t-butyldiphenylsilyl, triethylsilyl or 2,2,2-trichloroethoxycarbonyl.

17. The process of claim 12 , wherein in the desoxyepothilone precursor R is linear or branched chain alkyl substituted by hydroxy or OR 3 ; R A , R B and R 3 are each independently hydrogen, t-butyldimethylsilyl, t-butyldiphenylsilyl, triethylsilyl or 2,2,2-trichloroethoxycarbonyl.

18. The process of claim 12 , wherein in the desoxyepothilone precursor R is linear or branched chain alkyl substituted by NR 1 R 2 , wherein R 1 and R 2 are both hydrogen; R A and R B are each independently hydrogen, t-butyldimethylsilyl, t-butyldiphenylsilyl, triethylsilyl or 2,2,2-trichloroethoxycarbonyl.

19. The process of claim 12 , wherein in the desoxyepothilone precursor R is linear or branched chain alkyl substituted by cyclic acetal; R A and R B are each independently hydrogen, t-butyldimethylsilyl, t-butyldiphenylsilyl, triethylsilyl or 2,2,2-trichloroethoxycarbonyl.

20. The process of claim 12 , wherein in the desoxyepothilone precursor R is linear or branched chain alkyl substituted by a substituted carboxy group; R A and R B are each independently hydrogen, t-butyldimethylsilyl, t-butyldiphenylsilyl, triethylsilyl or 2,2,2-trichloroethoxycarbonyl.

21. A process of making a desoxyepothilone comprising:

reacting a desoxyepothilone precursor having the structure:

with a macrolactonization reagent, wherein the macrolactonization reagent is selected from the group consisting of acetic anhydride, pentafluorophenol, 2,4-dichlorobenzoyl chloride, and 2,4,6-trichlorobenzoyl chloride, to generate a desoxyepothilone having the structure:

wherein R is hydrogen; methyl; ethyl; n-propyl; n-hexyl; CO 2 Et;

 CH 2 OH; CH 2 OR 3 ; (CH 2 ) 3 —OH; or (CH 2 ) 3 —OR 3 ; and

R A , R B , and R 3 are each independently hydrogen; linear or branched, substituted or unsubstituted trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, or triarylsilyl or linear or branched, substituted or unsubstituted alkoxycarbonyl.

22. The process of claim 21 , wherein in the desoxyepothilone precursor, R A and R B are each independently hydrogen, t-butyldimethylsilyl, t-butyldiphenylsilyl, triethylsilyl or 2,2,2-trichloroethoxycarbonyl.

23. The process of claim 21 , wherein the step of reacting the desoxyepothilone precursor comprises macrolactonizing a desoxyepothilone precursor having the structure:

to generate a desoxyepothilone having the structure:

wherein R A and R B are each independently hydrogen, t-butyldimethylsilyl, t-butyldiphenylsilyl, triethylsilyl or 2,2,2-trichloroethoxycarbonyl.

24. The process of claim 21 , wherein the step of reacting the desoxyepothilone precursor comprises macrolactonizing a desoxyepothilone precursor having the structure:

to generate a desoxyepothilone having the structure:

wherein R 3 , R A and R B are each independently hydrogen, t-butyldimethylsilyl, t-butyldiphenylsilyl, triethylsilyl or 2,2,2-trichloroethoxycarbonyl.

25. The process of claim 21 , wherein the step of reacting the desoxyepothilone precursor comprises macrolactonizing a desoxyepothilone precursor having the structure:

to generate a desoxyepothilone having the structure:

wherein R A and R B are each independently hydrogen, t-butyldimethylsilyl, t-butyldiphenylsilyl, triethylsilyl or 2,2,2-trichloroethoxycarbonyl.

26. The process of claim 23 , wherein the macrolactonization reagent is acetic anhydride.

27. The process of claim 23 , wherein the macrolactonization reagent is pentafluorophenol.

28. The process of claim 23 , wherein the macrolactonization reagent is 2,4-dichlorobenzoyl chloride.

29. The process of claim 23 , wherein the macrolactonization reagent is 2,4,6-trichlorobenzoyl chloride.

30. The process of claim 1 , 9 , 12 , 21 , 23 , 24 , or 25 , wherein the macrolactonization reagent is 2,4,6-trichlorobenzoyl chloride in the presence of a tertiary amine selected from the group consisting of triethylamine, tri-n-propylamine, diisopropylethylamine, and diethylisopropylamine and optionally reacting in the presence of pyridine or N,N-dimethylaminopyridine.

31. The process of claim 9 , wherein in the desoxyepothilone precursor, R 0 is hydrogen, R′ is methyl, and R is selected from the group consisting of hydrogen or methyl.

32. A process of making an epothilone comprising:

(a) reacting an epothilone precursor having the structure:

 with a macrolactonization reagent, wherein the macrolactonization reagent is selected from the group consisting of acetic anhydride, pentafluorophenol, 2,4-dichlorobenzoyl chloride, and 2,4,6-trichlorobenzoyl chloride, to generate an epothilone having the structure:

wherein R, R 0 and R′ are independently H, linear or branched chain alkyl, optionally substituted by hydroxy, OR 3 , alkoxy, carboxy, carboxaldehyde, linear or branched alkyl or cyclic acetal, fluorine, NR 1 R 2 , N-hydroximino, or N-alkoxyimino, wherein R 1 and R 2 are independently H, phenyl, benzyl, linear or branched chain alkyl; and R 3 is hydrogen, substituted or unsubstituted trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, or triarylsilyl;

R″ is —CY═CHX, or H, linear or branched chain alkyl, phenyl, 2-methyl-1,3-thiazol-4-yl, 2-furanyl, 3-furanyl, 4-furanyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, imidazolyl, 2-methyl-1,3-oxazol-4-yl, 3-indolyl or 6-indolyl; Y is H or linear or branched chain alkyl; and X is H, linear or branched chain alkyl, phenyl, 2-methyl-1,3-thiazol-4-yl, 2-furanyl, 3-furanyl, 4-furanyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, imidazolyl, 2-methyl-1,3-oxazol-4-yl, 3-indolyl or 6-indolyl; wherein Y is H or linear or branched chain alkyl;

R A is hydrogen or a linear or branched alkyl, substituted or unsubstituted alkoxyalkyl, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted aryloxyalkyl, trialkylsilyl, aryldialkylsilyl, diarylalkylsilyl, triarylsilyl, linear or branched acyl, substituted or unsubstituted aroyl or benzoyl;

R B is hydrogen, substituted or unsubstituted alkoxycarbonyl, t-butyloxycarbonyl, amyloxycarbonyl, (trialkylsilyl)alkyloxycarbonyl, (dialkylarylsilyl)alkoxycarbonyl, benzyl, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, a linear or branched acyl, or substituted or unsubstituted aroyl or benzoyl; and

n is 2or 3.

33. The process of claim 32 ,

wherein the step of reacting an epothilone precursor comprises macrolactonizing an epothilone precursor having the structure:

 to generate an epothilone having the structure:

wherein R, R 0 and R′ are independently H, linear or branched chain alkyl, optionally substituted by hydroxy, OR 3 , alkoxy, carboxy, carboxaldehyde, linear or branched alkyl or cyclic acetal, fluorine, NR 1 R 2 , N-hydroximino, or N-alkoxyimino, wherein R 1 and R 2 are independently H, phenyl, benzyl, linear or branched chain alkyl; and R 3 is hydrogen, substituted or unsubstituted trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, or triarylsilyl;

R A is hydrogen or a linear or branched alkyl, substituted or unsubstituted alkoxyalkyl, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted aryloxyalkyl, trialkylsilyl, aryldialkylsilyl, diarylalkylsilyl, triarylsilyl, linear or branched acyl, substituted or unsubstituted aroyl or benzoyl;

R B is hydrogen, substituted or unsubstituted alkoxycarbonyl, t-butyloxycarbonyl, amyloxycarbonyl, (trialkylsilyl)alkyloxycarbonyl, (dialkylarylsilyl)alkoxycarbonyl, benzyl, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, a linear or branched acyl, or substituted or unsubstituted aroyl or benzoyl.

34. The process of claim 32 ,

wherein the step of reacting an epothilone precursor comprises macrolactonizing an epothilone precursor having the structure:

 to generate an epothilone having the structure:

wherein R, R 0 and R′ are independently H, linear or branched chain alkyl, optionally substituted by hydroxy, OR 3 , alkoxy, carboxy, carboxaldehyde, linear or branched alkyl or cyclic acetal, fluorine, NR 1 R 2 , N-hydroximino, or N-alkoxyimino, wherein R 1 and R 2 are independently H, phenyl, benzyl, linear or branched chain alkyl; and R 3 is hydrogen, substituted or unsubstituted trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, or triarylsilyl;

R A is hydrogen or a linear or branched alkyl, substituted or unsubstituted alkoxyalkyl, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted aryloxyalkyl, trialkylsilyl, aryldialkylsilyl, diarylalkylsilyl, triarylsilyl, linear or branched acyl, substituted or unsubstituted aroyl or benzoyl;

R B is hydrogen, substituted or unsubstituted alkoxycarbonyl, t-butyloxycarbonyl, amyloxycarbonyl, (trialkylsilyl)alkyloxycarbonyl, (dialkylarylsilyl)alkoxycarbonyl, benzyl, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, a linear or branched acyl, or substituted or unsubstituted aroyl or benzoyl.

35. The process of claim 34 , wherein in the epothilone precursor R is methyl.

36. The he process of claim 34 , wherein in the epothilone precursor R is hydrogen.

37. A process of making a desoxyepothilone comprising:

(a) reducing a desoxyepothilone precursor having the structure:

 to generate a desoxyepothilone precursor having the structure:

(b) hydrolyzing a desoxyepothilone precursor having the structure:

 to generate a desoxyepothilone precursor having the structure:

(c) reacting a desoxyepothilone precursor having the structure:

 with a macrolactonization reagent, wherein the macrolactonization reagent is selected from the group consisting of acetic anhydride, pentafluorophenol, 2,4-dichlorobenzoyl chloride, and 2,4,6-trichlorobenzoyl chloride, to generate a desoxyepothilone having the structure:

wherein R, R 0 and R′ are independently H, linear or branched chain alkyl, optionally substituted by hydroxy, OR 3 , alkoxy, carboxy, carboxaldehyde, linear or branched alkyl or cyclic acetal, fluorine, NR 1 R 2 , N-hydroximino, or N-alkoxyimino, wherein R 1 and R 2 are independently H, phenyl, benzyl, linear or branched chain alkyl; and R 3 is hydrogen, substituted or unsubstituted trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, or triarylsilyl;

R″ is —CY═CHX, or H, linear or branched chain alkyl, phenyl, 2-methyl-1,3-thiazol-4-yl, 2-furanyl, 3-furanyl, 4-furanyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, imidazolyl, 2-methyl-1,3-oxazol-4-yl, 3-indolyl or 6-indolyl; Y is H or linear or branched chain alkyl; and X is H, linear or branched chain alkyl, phenyl, 2-methyl-1,3-thiazol-4-yl, 2-furanyl, 3-furanyl, 4-furanyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, imidazolyl, 2-methyl-1,3-oxazol4-yl, 3-indolyl or 6-indolyl; wherein Y is H or linear or branched chain alkyl;

R A is hydrogen or a linear or branched alkyl, substituted or unsubstituted alkoxyalkyl, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted aryloxyalkyl, trialkylsilyl, aryldialkylsilyl, diarylalkylsilyl, triarylsilyl, linear or branched acyl, substituted or unsubstituted aroyl or benzoyl;

R B is hydrogen, substituted or unsubstituted alkoxycarbonyl, t-butyloxycarbonyl, amyloxycarbonyl, (trialkylsilyl)alkyloxycarbonyl, (dialkylarylsilyl)alkoxycarbonyl, benzyl, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, a linear or branched acyl, or substituted or unsubstituted aroyl or benzoyl;

R C is tertiary alkyl;

P is a linear or branched alkyl, alkoxyalkyl, substituted or unsubstituted aryloxyalkyl, trialkylsilyl, aryldialkylsilyl, diarylalkylsilyl or triarylsilyl; and

n is 2or 3.

38. A process of making a desoxyepothilone comprising:

(a) reducing a desoxyepothilone precursor having the structure:

 to generate a desoxyepothilone precursor having the structure:

(b) reducing a desoxyepothilone precursor having the structure:

 to generate a desoxyepothilone precursor having the structure:

(c) etherifying and hydrolyzing a desoxyepothilone precursor having the structure:

 to generate a desoxyepothilone precursor having the structure:

(d) reacting a desoxyepothilone precursor having the structure:

 with a macrolactonization reagent, wherein the macrolactonization reagent is selected from the group consisting of acetic anhydride, pentafluorophenol, 2,4-dichlorobenzoyl chloride, and 2,4,6-trichlorobenzoyl chloride, to generate a desoxyepothilone having the structure:

wherein R, R 0 and R″ are independently H, linear or branched chain alkyl, optionally substituted by hydroxy, OR 3 , alkoxy, carboxy, carboxaldehyde, linear or branched alkyl or cyclic acetal, fluorine, NR 1 R 2 , N-hydroximino, or N-alkoxyimino, wherein R 1 and R 2 are independently H, phenyl, benzyl, linear or branched chain alkyl; and R 3 is hydrogen, substituted or unsubstituted trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, or triarylsilyl;

R″ is —CY═CHX, or H, linear or branched chain alkyl, phenyl, 2-methyl-1,3-thiazol-4-yl, 2-furanyl, 3-furanyl, 4-furanyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, imidazolyl, 2-methyl-3-oxazol-4-yl, 3-indolyl or 6-indolyl; Y is H or linear or branched chain alkyl; and X is H, linear or branched chain alkyl, phenyl, 2-methyl-1,3-thiazol-4-yl, 2-furanyl, 3-furanyl, 4-furanyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, imidazolyl, 2-methyl-1,3-oxazol4-yl, 3-indolyl or 6-indolyl; wherein Y is H or linear or branched chain alkyl;

R A is hydrogen or a linear or branched alkyl, substituted or unsubstituted alkoxyalkyl, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted aryloxyalkyl, trialkylsilyl, aryldialkylsilyl, diarylalkylsilyl, triarylsilyl, linear or branched acyl, substituted or unsubstituted aroyl or benzoyl;

R B is hydrogen, substituted or unsubstituted alkoxycarbonyl, t-butyloxycarbonyl, amyloxycarbonyl, (trialkylsilyl)alkyloxycarbonyl, (dialkylarylsilyl)alkoxycarbonyl, benzyl, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, a linear or branched acyl, or substituted or unsubstituted aroyl or benzoyl;

R C is tertiary alkyl;

P is a linear or branched alkyl, alkoxyalkyl, substituted or unsubstituted aryloxyalkyl, trialkylsilyl, aryldialkylsilyl, diarylalkylsilyl or triarylsilyl; and

n is 2 or 3.

39. The process of claim 37 or 38 , wherein R 0 is hydrogen, R′ is methyl, R is hydrogen or methyl; n is 3, and R″ is —CH 3 —CHX, wherein X is 1,3-thiazol4-yl or 1,3-oxazol-4-yl.

Assignments (1)

Priority Claims (1)

Continuity (14)