Claims
- 1. A method for synthesizing a functionalized olefin via a cross-metathesis reaction, comprising contacting (a) a first olefinic reactant directly or indirectly substituted with a functional group Fn selected from phosphonato, phosphoryl, phosphanyl, phosphino, sulfonato, C1-C20 alkylsulfanyl, C5-C20arylsulfanyl, C1-C20 alkylsulfonyl, C5-C20 arylsulfonyl, C1-C20 alkylsulfinyl, C5-C20 arylsulfinyl, sulfonamido, amino, amido, imino, nitro, nitroso, hydroxyl, C1-C20 alkoxy, C5-C20 aryloxy, C2-C20 alkoxycarbonyl, C5-C20 aryloxycarbonyl, carboxyl, carboxylato, mercapto, formyl, C1-C20 thioester, cyano, cyanato, carbamoyl, epoxy, styrenyl, silyl, silyloxy, silanyl, siloxazanyl, boronato, boryl, stannyl, and germyl, with (b) a second olefinic reactant in the presence of (c) a catalyst composed of a Group 8 transition metal alkylidene complex under conditions and for a time period effective to allow cross-metathesis to occur, wherein the catalyst has the structure of formula (VIA)
- 2. The method of claim 1, wherein the first olefinic reactant is directly substituted with the functional group.
- 3. The method of claim 1, wherein the first olefinic reactant is indirectly substituted with the functional group.
- 4. The method of claim 1, wherein the second olefinic reactant is also substituted with a functional group Fn.
- 5. The method of claim 1, wherein:
X1 and X2 are anionic ligands, and are optionally linked to form a cyclic group; L is a neutral electron donor ligand that is optionally linked to R2, X1, and/or X2 through a spacer moiety; and R3A and R4A are optionally linked to form a cyclic group.
- 6. The method of claim 5, wherein w, x, y and z are zero, X and Y are N, and R3A and R4A are linked to form -Q-, such that the catalyst has the structure of formula (VIB)
- 7. The method of claim 6, wherein Q has the structure —CR22R22A—CR23R23A— or —CR22═CR23—, wherein R22 R22A, R23, and R23A are independently selected from the group consisting of hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, substituted heteroatom-containing hydrocarbyl, and functional groups, and or wherein any two of R22, R22A, R23, and R23A may be linked together to form a substituted or unsubstituted, saturated or unsaturated ring.
- 8. The method of claim 7, wherein Q has the structure —CR22R22A—CR23R23A—, such that the catalyst has the structure of formula (VIC)
- 9. The method of claim 8, wherein:
M is Ru; X1 and X2 are independently selected from the group consisting of hydrogen, halide, C1-C20 alkyl, C5-C20 aryl, C1-C20 alkoxy, C5-C20 aryloxy, C3-C20 alkyldiketonate, C5aryldiketonate, C2-C20 alkoxycarbonyl, C5-C20 aryloxycarbonyl, C2-C20 acyl, C1-C20 alkylsulfonato, C5-C20 arylsulfonato, C1-C20 alkylsulfanyl, C5-C20 arylsulfanyl, C1-C20 alkylsulfinyl, or C5-C20 arylsulfinyl, any of which, with the exception of halide, are optionally further substituted with one or more groups selected from halide, C1-C6 alkyl, C1-C6 alkoxy, and phenyl; R1 is hydrogen and R2 is selected from the group consisting of C1-C20 alkyl, C2-C20 alkenyl, and aryl; L is a neutral electron donor ligand selected from the group consisting of phosphine, sulfonated phosphine, phosphite, phosphinite, phosphonite, arsine, stibine, ether, amine, amide, imine, sulfoxide, carboxyl, nitrosyl, pyridine, substituted pyridine, imidazole, substituted imidazole, pyrazine, and thioether; R3 and R4 are aromatic, substituted aromatic, heteroaromatic, substituted heteroaromatic, alicyclic, substituted alicyclic, heteroatom-containing alicyclic, or substituted heteroatom-containing alicyclic, composed of from one to about five rings; and R8 and R9, are hydrogen, and R3A and R9A are selected from hydrogen, lower alkyl and phenyl, or are linked to form a cyclic group.
- 10. The method of claim 9, wherein:
R1 is hydrogen, and R2 is phenyl, vinyl, methyl, isopropyl, or t-butyl, optionally substituted with one or more moieties selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, phenyl, and a functional group Fn, wherein Fn is phosphonato, phosphoryl, phosphanyl, phosphino, sulfonato, C1-C20 alkylsulfanyl, C5-C20arylsulfanyl, C1-C20 alkylsulfonyl, C5-C20 arylsulfonyl, C1-C20 alkylsulfinyl, C5-C20 arylsulfinyl, sulfonamido, amino, amido, imino, nitro, nitroso, hydroxyl, C1-C20 alkoxy, C5-C20aryloxy, C2-C20 alkoxycarbonyl, C1-C20 aryloxycarbonyl, carboxyl, carboxylato, mercapto, formyl, C1-C20 thioester, cyano, cyanato, carbamoyl, epoxy, styrenyl, silyl, silyloxy, silanyl, siloxazanyl, boronato, boryl, halogen, stannyl, or germyl; and L is a phosphine of the formula L is a phosphine of the formula PR27R28R29, where R27, R28, and R29 are each independently aryl or C1-C10 alkyl.
- 11. The method of claim 10, wherein:
X1 and X2 are independently selected from the group consisting of halide, CF3CO2, CH3CO2, CFH2CO2, (CH3)3CO, (CF3)2(CH3)CO, (CF3)(CH3),2CO, PhO, MeO, EtO, Tosylate, mesylate, and trifluoromethanesulfonate; L is selected from the group consisting of —P(cyclohexyl)3, —P(cyclopentyl)3, —P(isopropyl)3, —P(phenyl)3, P(phenyl)3, —P(phenyl)2(R7) and —P(phenyl)(R7)2, in which R7 is lower alkyl; and R3 and R4 are the same and are either aromatic or C7-C12 alicyclic, if aromatic, each having the structure of formula (XI) 181 in which R24, R25, and R26 are each independently hydrogen, C1-Cl alkyl, C1-C10 alkoxy, aryl, substituted aryl, halogen, or a functional group.
- 12. The method of claim 11, wherein:
X1 and X2 are halide; R2 is hydrogen or 2,2-dimethylvinyl; R3 and R4 are mesityl, diisopinocamphenyl, or 2,4,2′,6′-tetramethylbiphenylyl; L is selected from the group consisting of —P(cyclohexyl)3 and —P(cyclopentyl)3; and R22 and R23 are hydrogen.
- 13. The method of claim 1, wherein the first olefinic reactant has the structure of formula (VIII)
- 14. The method of claim 13, wherein n is zero.
- 15. The method of claim 14, wherein Fn is a phosphonate.
- 16. The method of claim 15, wherein R5, R6 and R7 are hydrogen, such that the first olefinic reactant is a vinylphosphonate having the structure of formula (XII)
- 17. The method of claim 14, wherein n is 1.
- 18. The method of claim 17, wherein Fn is a phosphonate, a hydroxyl group, or boronate.
- 19. The method of claim 18, wherein Z is methylene, and R5, R6 and R7 are hydrogen.
- 20. The method of claim 13, wherein the second olefinic reactant has the molecular structure R18R19C═CR20R21wherein R18, R19, R20, and R21are independently selected group consisting of hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, substituted heteroatom-containing hydrocarbyl, and functional groups Fn.
- 21. A method for synthesizing a plurality of structurally diverse functionalized olefins from a common olefinic reactant via a cross-metathesis reaction, comprising:
(a) contacting an olefinic substrate with a first olefinic reactant in the presence of a catalyst composed of a Group 8 transition metal alkylidene complex containing an N-heterocyclic carbene ligand, under conditions and for a time period effective to allow cross-metathesis to occur, wherein the olefinic substrate is substituted with at least one -(Z)n-Fn moiety in which n is zero or 1, Z is a hydrocarbylene or a substituted and/or heteroatom-containing hydrocarbylene linking group, and Fn is selected from phosphonato, phosphoryl, phosphanyl, phosphino, sulfonato, C1-C20 alkylsulfanyl, C5-C20 arylsulfanyl, C1-C20 alkylsulfonyl, C5-C20 arylsulfonyl, C1-C20 alkylsulfinyl, C5-C20 arylsulfinyl, sulfonamido, amino, amido, imino, nitro, nitroso, hydroxyl, C1-C20 alkoxy, C5-C20 aryloxy, C2-C20 alkoxycarbonyl, C5-C20 aryloxycarbonyl, carboxyl, carboxylato, mercapto, formyl, C1-C20 thioester, cyano, cyanato, carbamoyl, epoxy, styrenyl, silyl, silyloxy, silanyl, siloxazanyl, boronato, boryl, stannyl, and germyl; (b) in a separate reaction, contacting the first olefinic reactant with a second olefinic reactant having a molecular structure that is different from that of the first olefinic reactant, in the presence of the Group 8 transition metal alkylidene complex, under conditions and for a time period effective to allow cross-metathesis to occur; and (c) optionally repeating step (b) with a plurality of olefinic reactants each having a different molecular structure.
- 22. The method of claim 21, wherein the second olefinic reactant is also substituted with at least one -(Z)n-Fn moiety.
- 23. A method for synthesizing a directly halogenated olefin via an olefin metathesis reaction, comprising:
contacting a directly halogenated olefinic reactant with a second olefinic species in the presence of a catalyst composed of a Group 8 transition metal alkylidene complex, under conditions and for a time period effective to allow metathesis to occur.
- 24. The method of claim 23, wherein the olefin cross metathesis reaction is a cross metathesis reaction.
- 25. The method of claim 24, wherein the catalyst has the structure of formula (VIA)
- 26. The method of claim 25, wherein:
X1 and X2 are anionic ligands, and are optionally linked to form a cyclic group; L is a neutral electron donor ligand that is optionally linked to R2, X1, and/or X2 through a spacer moiety; and R3A and R4A are optionally linked to form a cyclic group.
- 27. The method of claim 26, wherein w, x, y and z are zero, X and Y are N, and R3A and R4A are linked to form -Q-, such that the catalyst has the structure of formula (VIB)
- 28. The method of claim 27, wherein Q has the structure —CR22R22A—CR23R23A— or —CR22=CR23—, wherein R22, R22A, R23, and R23A are independently selected from the group consisting of hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, substituted heteroatom-containing hydrocarbyl, and functional groups, and or wherein any two of R22, R22A, R23, and R23A may be linked together to form a substituted or unsubstituted, saturated or unsaturated ring.
- 29. The method of claim 28, wherein Q has the structure —CR22R22CR23R23A—, such that the catalyst has the structure of formula (VIC)
- 30. The method of claim 29, wherein:
M is Ru; X1 and X2 may be the same or different, and are selected from the group consisting of hydrogen, halide, C1-C20 alkyl, C5-C20 aryl, C1-C20 alkoxy, C5-C20 aryloxy, C3-C20 alkyldiketonate, C5-C20 aryldiketonate, C2-C20 alkoxycarbonyl, C5-C20 aryloxycarbonyl, C2-C20 acyl, C1-C20 alkylsulfonato, C5-C20 arylsulfonato, C1-C20 alkylsulfanyl, C5-C20 arylsulfanyl, C1-C20 alkylsulfinyl, or C5-C20 arylsulfinyl, any of which, with the exception of halide, are optionally further substituted with one or more groups selected from halide, C1-C6 alkyl, C1-C6 alkoxy, and phenyl; R1 is hydrogen and R2 is selected from the group consisting of C1-C20 alkyl, C2-C20 alkenyl, and aryl; L is a neutral electron donor ligand selected from the group consisting of phosphine, sulfonated phosphine, phosphite, phosphinite, phosphonite, arsine, stibine, ether, amine, amide, imine, sulfoxide, carboxyl, nitrosyl, pyridine, substituted pyridine, imidazole, substituted imidazole, pyrazine, and thioether; R3 and R4 are aromatic, substituted aromatic, heteroaromatic, substituted heteroaromatic, alicyclic, substituted alicyclic, heteroatom-containing alicyclic, or substituted heteroatom-containing alicyclic, composed of from one to about five rings; and R8 and R9 are hydrogen, and R8A and R9A are selected from hydrogen, lower alkyl and phenyl, or are linked to form a cyclic group.
- 31. The method of claim 30, wherein:
R1 is hydrogen, and R2 is phenyl, vinyl, methyl, isopropyl, or t-butyl, optionally substituted with one or more moieties selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, phenyl, and a functional group Fn, wherein Fn is phosphonato, phosphoryl, phosphanyl, phosphino, sulfonato, C1-C20 alkylsulfanyl, C1-C20 arylsulfanyl, C1-C20 alkylsulfonyl, C1-C20 arylsulfonyl, C1-C20 alkylsulfinyl, C5-C20 arylsulfinyl, sulfonamido, amino, amido, imino, nitro, nitroso, hydroxyl, C1-C20 alkoxy, C5-C20 aryloxy, C2-C20 alkoxycarbonyl, C5-C20 aryloxycarbonyl carboxyl, carboxylato, mercapto, formyl, C1-C20 thioester, cyano, cyanato, carbamoyl, epoxy, styrenyl, silyl, silyloxy, silanyl, siloxazanyl, boronato, boryl, halogen, stannyl, or germyl; and L is a phosphine of the formula L is a phosphine of the formula PR27R28R29, where R27, R28 , and R29 are each independently aryl or C1-C10 alkyl.
- 32. The method of claim 31, wherein:
X1 and X2 are independently selected from the group consisting of halide, CF3CO2, CH3CO2, CFH2CO2, (CH3)3CO, (CF3)2(CH3)CO, (CF3)(CH3).2CO, PhO, MeO, EtO, tosylate, mesylate, and trifluoromethanesulfonate; L is selected from the group consisting of —P(cyclohexyl)3, —P(cyclopentyl)3, —P(isopropyl)3, —P(phenyl)3, P(phenyl)3, —P(phenyl)2(R7) and —P(phenyl)(R7)2, in which R7 is lower alkyl; and R3 and R4 are the same and are either aromatic or C7-C12 alicyclic, if aromatic, each having the structure of formula (XI) 187 in which R24, R25, and R26 are each independently hydrogen, C1-C10 alkyl, C1-C10 alkoxy, aryl, substituted aryl, halogen, or a functional group.
- 33. The method of claim 32, wherein:
X1 and X2 are halide; R2 is hydrogen or 2,2-dimethylvinyl; R3 and R4 are mesityl; L is selected from the group consisting of —P(cyclohexyl)3 and —P(cyclopentyl)3; and R22 and R23 are hydrogen.
- 34. The method of claim 24, wherein the directly halogenated olefinic reactant has the structure of formula (IX)
- 35. The method of claim 34, wherein at least one of R8, R9, and R10 is a halogen atom.
- 36. The method of claim 35, where X3 and at least one of R8, R9, and R10 is chloro or fluoro.
- 37. The method of claim 34, where X3 is chloro or fluoro, R8 and R9 are hydrogen or lower alkyl, and R10 is hydrogen, lower alkyl, chloro, or fluoro.
- 38. The method of claim 34, wherein the second olefinic reactant has the molecular structure R18R19C═CR20R21 wherein R18, R19, R20, and R21 are independently selected group consisting of hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, and substituted heteroatom-containing hydrocarbyl.
- 39. A method for synthesizing a substituted olefin via a cross-metathesis reaction, comprising:
contacting a substituted olefin selected from the group consisting of geminal disubstituted olefins and quaternary allylic olefins with an olefinic reactant in the presence of a catalyst composed of a Group 8 transition metal alkylidene complex containing an N-heterocyclic carbene ligand, under conditions and for a time period effective to allow cross-metathesis to occur.
- 40. The method of claim 39, wherein the catalyst has the structure of formula (VIA)
- 41. The method of claim 40, wherein:
X1 and X2 are anionic ligands, and are optionally linked to form a cyclic group; L is a neutral electron donor ligand that is optionally linked to R2, X1, and/or X2 through a spacer moiety; and R3A and R4A are optionally linked to form a cyclic group.
- 42. The method of claim 41, wherein w, x, y and z are zero, X and Y are N, and R3A and R4A are linked to form -Q-, such that the catalyst has the structure of formula (VIB)
- 43. The method of claim 42, wherein Q has the structure —CR22R22A—CR23R23A— or —CR22═CR23—, wherein R22, R22A, R23, and R23A are independently selected from the group consisting of hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, substituted heteroatom-containing hydrocarbyl, and functional groups, and or wherein any two of R22, R22A, R23, and R23A may be linked together to form a substituted or unsubstituted, saturated or unsaturated ring.
- 44. The method of claim 43, wherein Q has the structure —CR22R22A—CR23R23A—, such that the catalyst has the structure of formula (VIC)
- 45. The method of claim 44, wherein:
M is Ru; X1 and X2 may be the same or different, and are selected from the group consisting of hydrogen, halide, C1-C20 alkyl, C5-C20 aryl, C1-C20 alkoxy, C5-C20 aryloxy, C3-C20 alkyl C5-C20 aryldiketonate, C2-C20 alkoxycarbonyl, C5-C20 aryloxycarbonyl, C2-C20 acyl, C1-C20 alkylsulfonato, C5-C2 arylsulfonato, C1-C20 alkylsulfanyl, C5-C20 arylsulfanyl, C1-C20 alkylsulfinyl, or C5-C20 arylsulfinyl, any of which, with the exception of halide, are optionally further substituted with one or more groups selected from halide, C1-C6 alkyl, C1-C6 alkoxy, and phenyl; R1 is hydrogen and R2 is selected from the group consisting of C1-C20 alkyl, C2-C20 alkenyl, and aryl; L is a neutral electron donor ligand selected from the group consisting of phosphine, sulfonated phosphine, phosphite, phosphinite, phosphonite, arsine, stibine, ether, amine, amide, imine, sulfoxide, carboxyl, nitrosyl, pyridine, substituted pyridine, imidazole, substituted imidazole, pyrazine, and thioether; R3 and R4 are aromatic, substituted aromatic, heteroaromatic, substituted heteroaromatic, alicyclic, substituted alicyclic, heteroatom-containing alicyclic, or substituted heteroatom-containing alicyclic, composed of from one to about five rings; and R8 and R9, are hydrogen, and R8A and R9A are selected from hydrogen, lower alkyl and phenyl, or are linked to form a cyclic group.
- 46. The method of claim 45, wherein:
R1 is hydrogen, and R2 is phenyl, vinyl, methyl, isopropyl, or t-butyl, optionally substituted with one or more moieties selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, phenyl, and a functional group Fn, wherein Fn is phosphonato, phosphoryl, phosphanyl, phosphino, sulfonato, C1-C20 alkylsulfanyl, C5-C20 arylsulfanyl, C1-C20 alkylsulfonyl, C5-C20 arylsulfonyl, C1-C20 alkylsulfinyl, C5-C20arylsulfinyl, sulfonamido, amino, amido, imino, nitro, nitroso, hydroxyl, C1-C20 alkoxy, C1-C20 aryloxy, C2-C20 alkoxycarbonyl, C1-C20 aryloxycarbonyl, carboxyl, carboxylato, mercapto, formyl, C1-C20 thioester, cyano, cyanato, carbamoyl, epoxy, styrenyl, silyl, silyloxy, silanyl, siloxazanyl, boronato, boryl, halogen, stannyl, or germyl; and L is a phosphine of the formula L is a phosphine of the formula PR27R28R29, where R27, R28, and R29 are each independently aryl or C1-C10 alkyl.
- 47. The method of claim 46, wherein:
X1 and X2 are independently selected from the group consisting of halide, CF3CO2, CH3CO2, CFH2CO2, (CH3).3CO, (CF3)2(CH3)CO, (CF3)(CH3)2CO, PhO, MeO, EtO, tosylate, mesylate, and trifluoromethanesulfonate; L is selected from the group consisting of —P(cyclohexyl)3, —P(cyclopentyl)3, —P(isopropyl)3, —(Phenyl)3, P(phenyl)3, —P(phenyl)2(R7) and —P(phenyl)(R7)2, in which R7 is lower alkyl; and R3 and R4 are the same and are either aromatic or C7-C12 alicyclic, if aromatic, each having the structure of formula (XI) 192 in which R24, R25, and R26 are each independently hydrogen, C1-C10 alkyl, C1-C10 alkoxy, aryl, substituted aryl, halogen, or a functional group.
- 48. The method of claim 47, wherein:
X1 and X2 are halide; R2 is hydrogen or 2,2-dimethylvinyl; R3 and R4 are mesityl, diisopinocamphenyl, or 2,4,2′,6′-tetramethylbiphenylyl; L is selected from the group consisting of —P(cyclohexyl)3 and —P(cyclopentyl)3; and R22 and R23 are hydrogen.
- 49. The method of claim 39, wherein the substituted olefin is a geminal disubstituted olefin.
- 50. The method of claim 49, wherein the substituted olefin has the structure of formula (X)
- 51. The method of claim 50, wherein the substituted olefin is a quaternary allylic olefin.
- 52. The method of claim 51, wherein the substituted olefin has the structure of formula
- 53. A method for carrying out an olefin cross-metathesis reaction so as to provide a preponderance of a cis-1,2-disubstituted olefin in the reaction product, comprising:
contacting a cis-1,2-disubstituted olefinic reactant with a second olefinic reactant in the presence of a catalyst composed of a Group 8 transition metal alkylidene complex containing an N-heterocyclic carbene ligand, under conditions and for a time period effective to allow cross-metathesis to occur, wherein the N-heterocyclic carbene ligand is substituted with two or more bicyclic or polycyclic moieties.
- 54. The method of claim 53, wherein the bicyclic or polycyclic moieties are aliphatic.
- 55. The method of claim 54, wherein the bicyclic or polycyclic moieties are selected from norbornyl, adamantyl, camphenyl, and isobornyl, any of which may be substituted.
- 56. The method of claim 55, wherein the N-heterocyclic carbene ligand is 1,3-(+)-diisopinocamphenyl-4,5-dihydroimidazol-2-ylidene.
- 57. The method of claim 53, wherein the bicyclic or polycyclic moieties are aromatic.
- 58. The method of claim 57, wherein the bicyclic or polycyclic moieties are biphenylyl or substituted biphenylyl.
- 59. The method of claim 58, wherein the N-heterocyclic carbene ligand is 1,3-bis-[2′,6′-dimethyl-3′-(2″,6″-dimethylphenyl)phenyl]-4,5-dihydroimidazol-2-ylidene.
- 60. A transition metal complex comprising a transition metal center coordinated to an N-heterocyclic carbene ligand substituted with two or more bicyclic or polycyclic moieties.
- 61. The transition metal complex of claim 60, wherein the bicyclic or polycyclic moieties are aliphatic.
- 62. The transition metal complex of claim 61, wherein the bicyclic or polycyclic moieties are selected from norbornyl, adamantyl, camphenyl, and isobornyl, any of which may be substituted.
- 63. The transition metal complex of claim 62, wherein the N-heterocyclic carbene ligand is 1,3-(+)-diisopinocamphenyl-4,5-dihydroimidazol-2-ylidene.
- 64. The transition metal complex of claim 60, wherein the bicyclic or polycyclic moieties are aromatic.
- 65. The transition metal complex of claim 64, wherein the bicyclic or polycyclic moieties are biphenylyl or substituted biphenylyl.
- 66. The transition metal complex of claim 65, wherein the N-heterocyclic carbene ligand is 1,3 -bis-[2′,6′-dimethyl-3′-(2″,6″-dimethylphenyl)phenyl]-4,5-dihydroimidazol-2ylidene.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority under 35 U.S.C. §119(e)(1) to the following provisional U.S. patent applications: Serial No. 60/280,590, filed Mar. 30, 2001; Serial No. 60/280,462, filed Mar. 30, 2001; Serial No. 60/284,213, filed Apr. 16, 2001; Serial No. 60/285,597, filed Apr. 20, 2001; and Serial No. 60/340,588, filed Dec. 14, 2001. The disclosures of the aforementioned applications are incorporated by reference in their entireties.
ACKNOWLEDGEMENT OF GOVERNMENT SUPPORT
[0002] This invention was developed with U.S. Government support under grant numbers 2 R01 GM31332 and 3 RO1 GM31332-16 awarded by the National Institutes of Health, and under grant number CHE 9809856 awarded by the National Science Foundation. The Government has certain rights in the invention.
Provisional Applications (5)
|
Number |
Date |
Country |
|
60280590 |
Mar 2001 |
US |
|
60280462 |
Mar 2001 |
US |
|
60284213 |
Apr 2001 |
US |
|
60285597 |
Apr 2001 |
US |
|
60340588 |
Dec 2001 |
US |