1. A chiral porphyrin compound having the structure of Formula (I):
wherein:
M is present or absent and when present is H2 or a transition metal;
R1, R2, R3, R4, R5 and R6 are each independently selected from the group consisting of a heteroatom-containing chiral moiety, H, alkyl, substituted alkyl, arylalkyl, aryl, and substituted aryl; and
at least one of R1, R2, R3, R4, R5 and R6 is a heteroatom-containing chiral moiety selected from the group consisting of (+)-estrone, (+)-dihydrocholesterol, R-(+)-1,1 \u2032-bi-2-naphthol, (R)-(+)-4-benzyl-2-oxazolidinone, (L)-phenylalanine methyl ester, 1-1\u2032-(R)-\u03b1-methylbenzyl-aziridine-2(R)-carboxamide, (R)-(\u2212)-2-methoxypropionamide, (S)-(+)-2-methoxypropionamide, (S)-(+)-2,2-dimethylcyclopropanecarboxamide, and L-(R)-lactamide; or
at least one of R1 and R6 is a group having the structure:
wherein:
R11 is selected from the group consisting of H, alkyl, substituted alkyl, alkoxy, substituted alkoxy, halogen, arylalkyl, aryl, and substituted aryl and wherein Y is selected from the group consisting of (+)-estrone, (+)-dihydrocholesterol, R-(+)-1,1\u2032-bi-2-naphthol, (R)-(+)-4-benzyl-2-oxazolidinone, (L)-phenylalanine methyl ester, 1-1\u2032-(R)-\u03b1-methylbenzyl-aziridine-2(R)-carboxamide, (R)-(\u2212)-2-methoxypropionamide, (S)-(+)-2,2-dimethylcyclopropanecarboxamide, and L-(R)-lactamide.
2. The compound according to claim 1, wherein M is selected from the group consisting of H2, Zn, Fe, Ni, Co, Mn, Ru, and Rh.
3. The compound according to claim 1, wherein M is Co.
4. The compound according to claim 1, wherein at least one of R1 and R6 is H.
5. The compound according to claim 1, wherein at least one of R1 and R6 is alkyl.
6. The compound according to claim 5, wherein at least one of R1and R6 is n-heptyl.
7. The compound according to claim 1, wherein at least one of R1 and R6 is aryl.
8. The compound according to claim 7, wherein at least one of R1 and R6 is phenyl.
9. The compound according to claim 1, wherein at least one of R1 and R6 is substituted aryl.
10. The compound according to claim 9, wherein at least one of R1 and R6 is selected from the group consisting of 2,6-dimethylphenyl, 2,4,6-trimethylphenyl, 3,5-di-tert-butylphenyl, 2,6-dimethoxyphenyl, 3,5-dimethoxyphenyl, 4-t-butylphenyl, 4-acetylphenyl, 4-trifluoromethylphenyl, and pentafluorophenyl.
11. The compound according to claim 1, wherein at least one of R1 and R6 is selected from the group consisting of (+)-estrone; (+)-dihydrocholesterol; R-(+)-1,1\u2032-bi-2-naphthol; (R)-(+)-4-benzyl-2-oxazolidinone; (L)-phenylalanine methyl ester; 1-1\u2032-(R)-\u03b1-methylbenzyl-aziridine-2(R)-carboxamide; (R)-(\u2212)-2-methoxypropionamide; (S)-(+)-2-methoxypropionamide; (S)-(+)-2,2-dimethylcyclopropanecarboxamide; and L-(R)-lactamide.
12. The compound according to claim 1, wherein each R6 is selected from the group consisting of (+)-estrone; (+)-dihydrocholesterol; R-(+)-1,1\u2032-bi-2-naphthol; (R)-(+)-4-benzyl-2-oxazolidinone; (L)-phenylalanine methyl ester; 1-1\u2032-(R)-\u03b1-methylbenzyl-aziridine-2(R)-carboxamide; (R)-(\u2212)-2-methoxypropionamide; (S)-(+)-2-methoxypropionamide; (S)-(+)-2,2- dimethylcyclopropanecarboxamide; and L-(R)-lactamide.
13. The chiral porphyrin of claim 1, wherein the chiral porphyrin has a structure selected from the group consisting of:
14. A chiral porphyrin compound having the structure:
wherein:
M is present or absent and when present is H2 or a transition metal;
R1, R2, R3, R4, R5, and R6 are each independently selected from the group consisting of H, alkyl, substituted alkyl, arylalkyl, aryl, and substituted aryl; and
wherein at least one of R1 and R6 has the structure:
wherein R11 is selected from the group consisting of H, alkyl, substituted alkyl, alkoxy, substituted alkoxy, halogen, arylalkyl, aryl, and substituted aryl, and Y is selected from the group consisting of (+)-estrone; (+)-dihydrocholesterol; R-(+)-1,1\u2032-bi-2-naphthol; (R)-(+)-4-benzyl-2-oxazolidinone; (L)-phenylalanine methyl ester; 1-1\u2032-(R)- \u03b1-methylbenzyl-aziridine-2(R)-carboxamide; (R)-(\u2212)-2-methoxypropionamide; (S)-(+)- 2-methoxypropionamide; (S)-(+)-2,2-dimethylcyclopropanecarboxamide; and L-(R)-lactamide.
15. The chiral porphyrin of claim 14, wherein the chiral porphyrin has a structure selected from the group consisting of:
16. A method of synthesizing a heteroatom-substituted chiral porphyrin compound of claim 1, comprising reacting a porphyrin precursor with a chiral reagent comprising a heteroatom, the porphyrin precursor having a structure of Formula II:
wherein:
R1, R2, R3, R4, R5 and R6 are each independently selected from the group consisting of X, H, alkyl, substituted alkyl, arylalkyl, aryl, and substituted aryl;
X is selected from the group consisting of halogen, trifluoromethanesulfonate (OTf), OTf-substituted aryl, haloaryl and haloalkyl, and at least one of R1, R2, R3, R4, R5 and R6 is X;
wherein the chiral reagent comprising a heteroatom has the structure H-Y and Y is a heteroatom-containing chiral moiety comprising at least one of N, O, S, and B; and
wherein the porphyrin precursor and chiral reagent comprising a heteroatom are reacted in the presence of a metal compound, a ligand, and a base to produce a heteroatom-substituted chiral porphyrin.
17. The method according to claim 16, wherein X is a halogen selected from the group consisting of Br, Cl, I and F.
18. The method according to claim 17, wherein X is Br.
19. The method according to claim 16, wherein at least one meso-position of the porphyrin precursor of Formula I is halogenated.
20. The method according to claim 16, wherein X is haloaryl.
21. The method according to claim 20, wherein the haloaryl is 2,6-dibromophenyl.
22. The method of claim 16, wherein the metal compound comprises a metal selected from the group consisting of Pd, Pt, Ni, or Cu.
23. The method according to claim 16, wherein the metal compound is a metal precursor compound selected from the group consisting of Pd(dba)2, Pd2(dba)3, Pd(OAc)2, PdCl2, Pd(TFA)2, and (CH3CN)2PdCl2.
24. The method of claim 16, wherein the base is selected from the group consisting of n-BuLi, LDA, NaNH2, NaOH, Et3N, NaOAc, KOt-Bu, NaOt-Bu, Cs2CO3, K2CO3, and K3PO4.
25. The method according to claim 16, wherein the ligand is selected from the group of ligands consisting of:
26. The method according to claim 16, wherein Y comprises a heteroatom-containing chiral moiety selected from the group consisting of NR7R8, OR9, SR10, and BR10 wherein R7, R8, R9, and R10 are each independently selected from the group consisting of H, alkyl, substituted alkyl, arylalkyl, alkoxyl, carboxyl, aryl, and substituted aryl.
27. The method according to claim 16, wherein Y is a selected from the group consisting of chiral amino, substituted chiral amino, chiral amido, substituted chiral amido, chiral alkoxy, substituted chiral alkoxy, chiral thio, substituted chiral thio, and chiral borate ester moieties.
28. The method according to claim 16, wherein Y is selected from the group consisting of (+)-estrone; (+)-dihydrocholesterol; R-(+)-1,1\u2032-bi-2-naphthol; (R)-(+)-4-benzyl-2-oxazolidinone; (L)-phenylalanine methyl ester; 1-1\u2032-(R)- \u03b1-methylbenzyl-aziridine-2(R)-carboxamide; (R)-(\u2212)-2-methoxypropionamide; (S)-(+)-2-methoxypropionamide; (S)-(+)-2,2-dimethylcyclopropanecarboxamide; and L-(R)-lactamide.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. An apparatus for controlling a physiological function comprising:
at least one electrode placed on, in, or near a targeted component of the pudendal nerve, andor its branch(es), andor its spinal root(s),
a controller coupled to the electrode to apply an electrical signal having an amplitude, the controller to apply the electrical signal to the electrode to selectively stimulate the targeted component, the controller being operable in a first mode to apply the electrical signal at a first frequency or range of frequencies without substantially changing the amplitude to achieve a first desired physiologic response, the controller being operable in a second mode to apply the electrical signal at a second frequency or range of frequencies without substantially changing the amplitude to achieve a second desired physiologic response different than the first physiologic response.
2. An apparatus according to claim 1
wherein the targeted component comprises a urethral afferent of the pudendal nerve andor afferent nerve fibers in the deep perineal nerve.
3. An apparatus according to claim 1
wherein the physiological function comprises one of controlling urinary incontinence and controlling micturition.
4. An apparatus for controlling a physiological function comprising:
at least one electrode placed on, in, or near a targeted component of the pudendal nerve, andor its branch(es), andor its spinal root(s),
a controller coupled to the electrode to apply an electrical signal having an amplitude, the controller to apply the electrical signal to the electrode to selectively stimulate the targeted component, the controller being operable in a first mode to apply the electrical signal at a first frequency or range of frequencies without substantially changing the amplitude to control micturition, the controller being operable in a second mode to apply the electrical signal at a second frequency or range of frequencies without substantially changing the amplitude to control urinary incontinence.
5. An apparatus for controlling a physiological function of the lower urinary tract comprising:
at least one electrode placed on, in, or near afferent nerve fibers in the deep perineal nerve,
a controller coupled to the electrode to apply an electrical signal having an amplitude, the controller to apply the electrical signal to the electrode to selectively stimulate the afferent nerve fibers in the deep perineal nerve, the controller being operable in a first mode to apply the electrical signal at a first frequency or range of frequencies without substantially changing the amplitude to achieve a first desired physiologic response, the controller being operable in a second mode to apply the electrical signal at a second frequency or range of frequencies without substantially changing the amplitude to achieve a second desired physiologic response different than the first physiologic response.
6. An apparatus according to claim 5
wherein the physiological function comprises one of controlling urinary incontinence and controlling micturition.