Substituted Cyclohexadienals - Syntheses and Applications

Abstract

The present invention is generally directed to the use of L-proline and certain derivatives thereof to catalyze the asymmetric self-condensation of α,β-unsaturated aldehydes to form homodimer and heterodimer cyclohexadienals. Reaction conditions are mild and yet amenable to a variety of different substrates yielding molecules with complex scaffolds from simple precursors. This approach allows for diversification and synthesis of this structural class of compounds in sufficient quantity, purity and enantioselectivity for, e.g., biological investigations and use as fluorescent probes, anti-cancer agents, anti-bacterial agents, and/or anti-fungal agents. The present invention is also generally directed to the cyclohexadienals produced.

Description

BRIEF DESCRIPTION OF THE FIGURES

The following figures form part of the present specification and are included to further demonstrate certain aspects of the present invention. The invention may be better understood by reference to one or more of these drawings in combination with the detailed description of specific embodiments presented herein.

FIG. 1. The self-condensation products of all-E-retinal (A) and citral (B).

FIG. 2. Non-limiting examples of homodimer cyclohexadienals produced according to the present invention.

FIG. 3. Non-limiting examples of heterodimer cyclohexadienals produced according to the present invention.

FIG. 4. Non-limiting examples of heterodimer cyclohexadienals produced according to the present invention.

FIG. 5. Non-limiting examples of heterodimer cyclohexadienals produced according to the present invention.

FIG. 6. Non-limiting examples of heterodimer cyclohexadienals produced according to the present invention.

FIG. 7. Non-limiting examples of heterodimer cyclohexadienals produced according to the present invention.

FIG. 8. Time course analysis of retinal homodimerization by NMR spectroscopy.

FIG. 9. Results of neurite outgrowth assay using certain compounds of the present invention (see Example 8).

FIG. 10. Anti-cancer assay results of certain compounds of the present invention (see Example 9).

FIGS. 11-14. Anti-bacterial assay results of certain compounds of the present invention (see Example 10).

FIGS. 15-16. Anti-fungal assay results of certain compounds of the present invention (see Example 10).

Claims

1. A method of preparing a cyclohexadienal comprising reacting an α,β-unsaturated aldehyde with a β-substituted α,β-unsaturated aldehyde in the presence of a compound of formula (I):

2. The method of claim 1, wherein the α,β-unsaturated aldehyde is of formula (II):

3. The method of claim 1, wherein the β-substituted α,β-unsaturated aldehyde is of formula (III):

4. The method of claim 1, wherein W is COORA.

5. The method of claim 4, wherein RA is H.

6. The method of claim 4, wherein RA is an alkyl group.

7. The method of claim 6, wherein the alkyl group is selected from the group consisting of methyl, isopropyl and benzyl.

8. The method of claim 1, wherein W is alkyl.

9. The method of claim 8, wherein the alkyl group is selected from the group consisting of —CH2OH, —C(H)(OH)((CH2)(CH3))2 and —C(H)(OH)(phenyl)2.

10. The method of claim 1, wherein X, Y and Z are each H.

11. The method of claim 1, wherein the compound of formula (I) is further defined as L-proline.

12. The method of claim 1, wherein the reaction method takes place in the presence of ethanol.

13. The method of claim 1, wherein the α,β-unsaturated aldehyde is the same compound as the β-substituted α,β-unsaturated aldehyde.

14. The method of claim 13, wherein the molar ratio of the α,β-unsaturated aldehyde to the β-substituted α,β-unsaturated aldehyde is about 1:1.5.

15. The method of claim 1, wherein the α,β-unsaturated aldehyde is a different compound than the β-substituted α,β-unsaturated aldehyde.

16. The method of claim 1, wherein R1, R2, R3, R4, R5 and R6 are each independently selected from the group consisting of H, alkyl, cycloalkyl and aryl.

17. The method of claim 1, wherein only one of R1, R2, R3, R4, R5 and R6 is H.

18. The method of claim 17, wherein only one of R2 and R3 is H.

19. The method of claim 1, wherein the cyclohexadienal is substantially pure.

20. The method of claim 1, wherein the cyclohexadienal is selected from the group consisting of 6-methyl-4,6-bis-(4-methyl-pent-3-enyl)-cyclohexa-1,3-dienecarbaldehyde; 6,6-dimethyl-4-(4-methyl-pent-3-enyl)-cyclohexa-1,3-dienecarbaldehyde; 6-methyl-4-(4-methyl-pent-3-enyl)-cyclohexa-1,3-dienecarbaldehyde; 4-(4-methyl-pent-3-enyl)-6-phenyl-cyclohexa-1,3-dienecarbaldehyde; 4-(4-methyl-pent-3-enyl)-6-(4-nitro-phenyl)-cyclohexa-1,3-dienecarbaldehyde; 6-(4-dimethylamino-phenyl)-4-(4-methyl-pent-3-enyl)-cyclohexa-1,3-dienecarbaldehyde; 4-(4-methyl-pent-3-enyl)-cyclohexa-1,3-dienecarbaldehyde; 6-methyl-4,6-bis-(5-methyl-furan-2-yl)-cyclohexa-1,3-dienecarbaldehyde; 4-(5-methyl-furan-2-yl)-6-phenyl-cyclohexa-1,3-dienecarbaldehyde; 4-(5-methyl-furan-2-yl)-6-(4-nitro-phenyl)-cyclohexa-1,3-dienecarbaldehyde; 6-(4-dimethylamino-phenyl)-4-(5-methyl-furan-2-yl)-cyclohexa-1,3-dienecarbaldehyde; 6-methyl-4,6-di-thiophen-2-yl-cyclohexa-1,3-dienecarbaldehyde; 6-(4-dimethylamino-phenyl)-4-thiophen-2-yl-cyclohexa-1,3-dienecarbaldehyde; 6-(4-nitro-phenyl)-4-thiophen-2-yl-cyclohexa-1,3-dienecarbaldehyde; 6-phenyl-4-thiophen-2-yl-cyclohexa-1,3-dienecarbaldehyde; 6-methyl-4-thiophen-2-yl-cyclohexa-1,3-dienecarbaldehyde; 6-(4-dimethylamino-phenyl)-4-(1H-indol-3-yl)-cyclohexa-1,3-dienecarbaldehyde; 4,6-bis-(1H-indol-3-yl)-6-methyl-cyclohexa-1,3-dienecarbaldehyde; 4-methyl-6-phenyl-cyclohexa-1,3-dienecarbaldehyde; 4-hept-1-enyl-6-methyl-cyclohexa-1,3-dienecarbaldehyde; 4,6-di-hept-1-enyl-6-methyl-cyclohexa-1,3-dienecarbaldehyde; 4,6-bis-biphenyl-4-yl-6-methyl-cyclohexa-1,3-dienecarbaldehyde; 4-biphenyl-4-yl-6-methyl-cyclohexa-1,3-dienecarbaldehyde; 4-biphenyl-4-yl-6-phenyl-cyclohexa-1,3-dienecarbaldehyde; 4-biphenyl-4-yl-6-(4-nitro-phenyl)-cyclohexa-1,3-dienecarbaldehyde; 4-biphenyl-4-yl-6-(4-dimethylamino-phenyl)-cyclohexa-1,3-dienecarbaldehyde; 4,6-bis-(9H-fluoren-2-yl)-6-methyl-cyclohexa-1,3-dienecarbaldehyde; 4-(9H-fluoren-2-yl)-6-methyl-cyclohexa-1,3-dienecarbaldehyde; 4-(9H-fluoren-2-yl)-6-phenyl-cyclohexa-1,3-dienecarbaldehyde; 6-(4-dimethylamino-phenyl)-4-(9H-fluoren-2-yl)-cyclohexa-1,3-dienecarbaldehyde; 4-(9H-fluoren-2-yl)-6-(4-nitro-phenyl)-cyclohexa-1,3-dienecarbaldehyde; 6-methyl-4-[2-(2,6,6-trimethyl-cyclohex-1-enyl)-vinyl]-cyclohexa-1,3-dienecarbaldehyde; 6-phenyl-4-[2-(2,6,6-trimethyl-cyclohex-1-enyl)-vinyl]-cyclohexa-1,3-dienecarbaldehyde; 6-(4-nitro-phenyl)-4-[2-(2,6,6-trimethyl-cyclohex-1-enyl)-vinyl]-cyclohexa-1,3-dienecarbaldehyde; 6-(4-dimethylamino-phenyl)-4-[2-(2,6,6-trimethyl-cyclohex-1-enyl)-vinyl]-cyclohexa-1,3-dienecarbaldehyde; 6-methyl-4,6-bis-[2-(2,6,6-trimethyl-cyclohex-1-enyl)-vinyl]-cyclohexa-1,3-dienecarbaldehyde; 6-methyl-6-[3-methyl-6-(2,6,6-trimethyl-cyclohex-1-enyl)-hexa-1,3,5-trienyl]-4-[4-methyl-6-(2,6,6-trimethyl-cyclohex-1-enyl)-hexa-1,3,5-trienyl]-cyclohexa-1,3-dienecarbaldehyde; 6-methyl-4-[4-methyl-6-(2,6,6-trimethyl-cyclohex-1-enyl)-hexa-1,3,5-trienyl]-cyclohexa-1,3-dienecarbaldehyde; 4-[4-methyl-6-(2,6,6-trimethyl-cyclohex-1-enyl)-hexa-1,3,5-trienyl]-6-phenyl-cyclohexa-1,3-dienecarbaldehyde; 6-(4-dimethylamino-phenyl)-4-[4-methyl-6-(2,6,6-trimethyl-cyclohex-1-enyl)-hexa-1,3,5-trienyl]-cyclohexa-1,3-dienecarbaldehyde; 4-[4-methyl-6-(2,6,6-trimethyl-cyclohex-1-enyl)-hexa-1,3,5-trienyl]-6-(4-nitro-phenyl)-cyclohexa-1,3-dienecarbaldehyde; 6-methyl-4-(4-methyl-pent-3-enyl)-6-thiophen-2-yl-cyclohexa-1,3-dienecarbaldehyde; 4-biphenyl-4-yl-6-methyl-6-(5-methyl-furan-2-yl)-cyclohexa-1,3-dienecarbaldehyde; 4,6-dihexyl-6-methyl-cyclohexa-1,3-dienecarbaldehyde; 4-hexyl-6-methyl-cyclohexa-1,3-dienecarbaldehyde; 4-biphenyl-4-yl-6-methyl-6-thiophen-2-yl-cyclohexa-1,3-dienecarbaldehyde; (E)-6,6-dimethyl-4-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)cyclohexa-1,3-dienecarbaldehyde; 6-methyl-6-(5-methylfuran-2-yl)-4-(4-methylpent-3-enyl)cyclohexa-1,3-dienecarbaldehyde; 6,6-dimethyl-4-(5-methylfuran-2-yl)cyclohexa-1,3-dienecarbaldehyde; 6-methyl-4-(naphthalen-2-yl)cyclohexa-1,3-dienecarbaldehyde; (E)-4-(4,8-dimethylnona-3,7-dienyl)-6-methylcyclohexa-1,3-dienecarbaldehyde; 5,6-dimethyl-4-(thiophen-2-yl)cyclohexa-1,3-dienecarbaldehyde; 5,6,6-trimethyl-4-(thiophen-2-yl)cyclohexa-1,3-dienecarbaldehyde; 6-(biphenyl-4-yl)-4,6-dimethylcyclohexa-1,3-dienecarbaldehyde; 6,6-dimethyl-4-(naphthalen-2-yl)cyclohexa-1,3-dienecarbaldehyde; 4-(biphenyl-4-yl)-6,6-dimethylcyclohexa-1,3-dienecarbaldehyde; 4,6,6-trimethylcyclohexa-1,3-dienecarbaldehyde; 5,6-dimethyl-4,6-di(thiophen-2-yl)cyclohexa-1,3-dienecarbaldehyde; 6-methyl-4,6-diphenylcyclohexa-1,3-dienecarbaldehyde; 6-methyl-4,6-di(naphthalen-2-yl)cyclohexa-1,3-dienecarbaldehyde; 4,6-bis((E)-4,8-dimethylnona-3,7-dienyl)-6-methylcyclohexa-1,3-dienecarbaldehyde; cis-4-methyl-5-(3-methyl-but-2-enyl)-6-phenyl-cyclohexa-1,3-dienecarbaldehyde; trans-4-methyl-5-(3-methyl-but-2-enyl)-6-phenyl-cyclohexa-1,3-dienecarbaldehyde; cis and trans-6-(4-dimethylamino-phenyl)-4-methyl-5-(3-methyl-but-2-enyl)-cyclohexa-1,3-dienecarbaldehyde; 6-(4-(dimethylamino)phenyl)-4-methylcyclohexa-1,3-dienecarbaldehyde; 4-methyl-6-(4-nitrophenyl)cyclohexa-1,3-dienecarbaldehyde; 4-methylcyclohexa-1,3-dienecarbaldehyde; 4-hexyl-6-phenylcyclohexa-1,3-dienecarbaldehyde; 6-(4-(dimethylamino)phenyl)-4-hexylcyclohexa-1,3-dienecarbaldehyde; 4,6-diphenylcyclohexa-1,3-dienecarbaldehyde; 6-(4-(dimethylamino)phenyl)-4-phenylcyclohexa-1,3-dienecarbaldehyde; 6-(4-nitrophenyl)-4-phenylcyclohexa-1,3-dienecarbaldehyde; 4-(naphthalen-2-yl)-6-phenylcyclohexa-1,3-dienecarbaldehyde; 6-(4-(dimethylamino)phenyl)-4-(naphthalen-2-yl)cyclohexa-1,3-dienecarbaldehyde; 4-(naphthalen-2-yl)-6-(4-nitrophenyl)cyclohexa-1,3-dienecarbaldehyde; 4-(naphthalen-2-yl)cyclohexa-1,3-dienecarbaldehyde; (E)-4-(4,8-dimethylnona-3,7-dienyl)cyclohexa-1,3-dienecarbaldehyde; (E)-4-(4,8-dimethylnona-3,7-dienyl)-6-phenylcyclohexa-1,3-dienecarbaldehyde; (E)-6-(4-(dimethylamino)phenyl)-4-(4,8-dimethylnona-3,7-dienyl)cyclohexa-1,3-dienecarbaldehyde; 5-methyl-6-(4-nitrophenyl)-4-(thiophen-2-yl)cyclohexa-1,3-dienecarbaldehyde; 6-(4-(dimethylamino)phenyl)-5-methyl-4-(thiophen-2-yl)cyclohexa-1,3-dienecarbaldehyde; 5-methyl-6-phenyl-4-(thiophen-2-yl)cyclohexa-1,3-dienecarbaldehyde; 5-methyl-4-(thiophen-2-yl)cyclohexa-1,3-dienecarbaldehyde; 5-(4-methyl-pent-3-enyl)-4′-nitro-biphenyl-2-carbaldehyde; 4″-dimethylamino-[1,1′;3′,1″]terphenyl-4′-carbaldehyde; 4′″-dimethylamino-[1,1′;4′,1″;3″,1′″]quaterphenyl-4″-carbaldehyde; 4′-dimethylamino-5-(9H-fluoren-2-yl)-biphenyl-2-carbaldehyde; 4′-(dimethylamino)-5-methylbiphenyl-2-carbaldehyde; 5-(9H-fluoren-2-yl)-biphenyl-2-carbaldehyde; and 5-(4-methyl-pent-3-enyl)-biphenyl-2-carbaldehyde.

21. The method of claim 1, wherein the cyclohexadienal is further comprised in a pharmaceutical composition.

22. A method of stimulating neurite growth, comprising administering to a cell an effective amount of a cyclohexadienal of claim 1.

23. The method of claim 22, wherein the cyclohexadienal comprises a substituent selected from the group consisting of naphthyl, biphenyl and farnesyl.

24. The method of claim 22, wherein the cyclohexadienal of claim 1 is further defined as 4-(biphenyl-4-yl)-6-methyl-6-(5-methylfuran-2-yl)cyclohexa-1,3-dienecarbaldehyde.

25. The method of claim 22, wherein the cyclohexadienal of claim 1 is further defined as 4,6-dihexyl-6-methylcyclohexa-1,3-dienecarbaldehyde.

26. The method of claim 22, wherein the cyclohexadienal of claim 1 is further defined as 6-(4-(dimethylamino)phenyl)-4-(naphthalen-2-yl)cyclohexa-1,3-dienecarbaldehyde.

27. In an improved method for reacting an α,β-unsaturated aldehyde with a β-substituted α,β-unsaturated aldehyde, the improvement comprising performing the reaction in the presence of a compound of formula (I):

28. A cyclohexadienal of formula (IV):

29. The cyclohexadienal of claim 28, wherein R1 is selected from the group consisting of alkyl, cycloalkyl and aryl.

30. The cyclohexadienal of claim 28, wherein R5 and R6 are independently selected from the group consisting of H, alkyl, cycloalkyl and aryl.

31. The cyclohexadienal of claim 30, wherein either R5 or R6 is an aryl group.

32. The cyclohexadienal of claim 31, wherein the aryl group is a phenyl group.

33. The cyclohexadienal of claim 28, wherein the cyclohexadienal is selected from the group consisting of 6-methyl-4,6-bis-(4-methyl-pent-3-enyl)-cyclohexa-1,3-dienecarbaldehyde; 6,6-dimethyl-4-(4-methyl-pent-3-enyl)-cyclohexa-1,3-dienecarbaldehyde; 6-methyl-4-(4-methyl-pent-3-enyl)-cyclohexa-1,3-dienecarbaldehyde; 4-(4-methyl-pent-3-enyl)-6-phenyl-cyclohexa-1,3-dienecarbaldehyde; 4-(4-methyl-pent-3-enyl)-6-(4-nitro-phenyl)-cyclohexa-1,3-dienecarbaldehyde; 6-(4-dimethylamino-phenyl)-4-(4-methyl-pent-3-enyl)-cyclohexa-1,3-dienecarbaldehyde; 4-(4-methyl-pent-3-enyl)-cyclohexa-1,3-dienecarbaldehyde; 6-methyl-4,6-bis-(5-methyl-furan-2-yl)-cyclohexa-1,3-dienecarbaldehyde; 4-(5-methyl-furan-2-yl)-6-phenyl-cyclohexa-1,3-dienecarbaldehyde; 4-(5-methyl-furan-2-yl)-6-(4-nitro-phenyl)-cyclohexa-1,3-dienecarbaldehyde; 6-(4-dimethylamino-phenyl)-4-(5-methyl-furan-2-yl)-cyclohexa-1,3-dienecarbaldehyde; 6-methyl-4,6-di-thiophen-2-yl-cyclohexa-1,3-dienecarbaldehyde; 6-(4-dimethylamino-phenyl)-4-thiophen-2-yl-cyclohexa-1,3-dienecarbaldehyde; 6-(4-nitro-phenyl)-4-thiophen-2-yl-cyclohexa-1,3-dienecarbaldehyde; 6-phenyl-4-thiophen-2-yl-cyclohexa-1,3-dienecarbaldehyde; 6-methyl-4-thiophen-2-yl-cyclohexa-1,3-dienecarbaldehyde; 6-(4-dimethylamino-phenyl)-4-(1H-indol-3-yl)-cyclohexa-1,3-dienecarbaldehyde; 4,6-bis-(1H-indol-3-yl)-6-methyl-cyclohexa-1,3-dienecarbaldehyde; 4-methyl-6-phenyl-cyclohexa-1,3-dienecarbaldehyde; 4-hept-1-enyl-6-methyl-cyclohexa-1,3-dienecarbaldehyde; 4,6-di-hept-1-enyl-6-methyl-cyclohexa-1,3-dienecarbaldehyde; 4,6-bis-biphenyl-4-yl-6-methyl-cyclohexa-1,3-dienecarbaldehyde; 4-biphenyl-4-yl-6-methyl-cyclohexa-1,3-dienecarbaldehyde; 4-biphenyl-4-yl-6-phenyl-cyclohexa-1,3-dienecarbaldehyde; 4-biphenyl-4-yl-6-(4-nitro-phenyl)-cyclohexa-1,3-dienecarbaldehyde; 4-biphenyl-4-yl-6-(4-dimethylamino-phenyl)-cyclohexa-1,3-dienecarbaldehyde; 4,6-bis-(9H-fluoren-2-yl)-6-methyl-cyclohexa-1,3-dienecarbaldehyde; 4-(9H-fluoren-2-yl)-6-methyl-cyclohexa-1,3-dienecarbaldehyde; 4-(9H-fluoren-2-yl)-6-phenyl-cyclohexa-1,3-dienecarbaldehyde; 6-(4-dimethylamino-phenyl)-4-(9H-fluoren-2-yl)-cyclohexa-1,3-dienecarbaldehyde; 4-(9H-fluoren-2-yl)-6-(4-nitro-phenyl)-cyclohexa-1,3-dienecarbaldehyde; 6-methyl-4-[2-(2,6,6-trimethyl-cyclohex-1-enyl)-vinyl]-cyclohexa-1,3-dienecarbaldehyde; 6-phenyl-4-[2-(2,6,6-trimethyl-cyclohex-1-enyl)-vinyl]-cyclohexa-1,3-dienecarbaldehyde; 6-(4-nitro-phenyl)-4-[2-(2,6,6-trimethyl-cyclohex-1-enyl)-vinyl]-cyclohexa-1,3-dienecarbaldehyde; 6-(4-dimethylamino-phenyl)-4-[2-(2,6,6-trimethyl-cyclohex-1-enyl)-vinyl]-cyclohexa-1,3-dienecarbaldehyde; 6-methyl-4,6-bis-[2-(2,6,6-trimethyl-cyclohex-1-enyl)-vinyl]-cyclohexa-1,3-dienecarbaldehyde; 6-methyl-6-[3-methyl-6-(2,6,6-trimethyl-cyclohex-1-enyl)-hexa-1,3,5-trienyl]-4-[4-methyl-6-(2,6,6-trimethyl-cyclohex-1-enyl)-hexa-1,3,5-trienyl]-cyclohexa-1,3-dienecarbaldehyde; 6-methyl-4-[4-methyl-6-(2,6,6-trimethyl-cyclohex-1-enyl)-hexa-1,3,5-trienyl]-cyclohexa-1,3-dienecarbaldehyde; 4-[4-methyl-6-(2,6,6-trimethyl-cyclohex-1-enyl)-hexa-1,3,5-trienyl]-6-phenyl-cyclohexa-1,3-dienecarbaldehyde; 6-(4-dimethylamino-phenyl)-4-[4-methyl-6-(2,6,6-trimethyl-cyclohex-1-enyl)-hexa-1,3,5-trienyl]-cyclohexa-1,3-dienecarbaldehyde; 4-[4-methyl-6-(2,6,6-trimethyl-cyclohex-1-enyl)-hexa-1,3,5-trienyl]-6-(4-nitro-phenyl)-cyclohexa-1,3-dienecarbaldehyde; 6-methyl-4-(4-methyl-pent-3-enyl)-6-thiophen-2-yl-cyclohexa-1,3-dienecarbaldehyde; 4-biphenyl-4-yl-6-methyl-6-(5-methyl-furan-2-yl)-cyclohexa-1,3-dienecarbaldehyde; 4,6-dihexyl-6-methyl-cyclohexa-1,3-dienecarbaldehyde; 4-hexyl-6-methyl-cyclohexa-1,3-dienecarbaldehyde; 4-biphenyl-4-yl-6-methyl-6-thiophen-2-yl-cyclohexa-1,3-dienecarbaldehyde; (E)-6,6-dimethyl-4-(2-(2,6,6-trimethylcyclohex-1-enyl)vinyl)cyclohexa-1,3-dienecarbaldehyde; 6-methyl-6-(5-methylfuran-2-yl)-4-(4-methylpent-3-enyl)cyclohexa-1,3-dienecarbaldehyde; 6,6-dimethyl-4-(5-methylfuran-2-yl)cyclohexa-1,3-dienecarbaldehyde; 6-methyl-4-(naphthalen-2-yl)cyclohexa-1,3-dienecarbaldehyde; (E)-4-(4,8-dimethylnona-3,7-dienyl)-6-methylcyclohexa-1,3-dienecarbaldehyde; 5,6-dimethyl-4-(thiophen-2-yl)cyclohexa-1,3-dienecarbaldehyde; 5,6,6-trimethyl-4-(thiophen-2-yl)cyclohexa-1,3-dienecarbaldehyde; 6-(biphenyl-4-yl)-4,6-dimethylcyclohexa-1,3-dienecarbaldehyde; 6,6-dimethyl-4-(naphthalen-2-yl)cyclohexa-1,3-dienecarbaldehyde; 4-(biphenyl-4-yl)-6,6-dimethylcyclohexa-1,3-dienecarbaldehyde; 4,6,6-trimethylcyclohexa-1,3-dienecarbaldehyde; 5,6-dimethyl-4,6-di(thiophen-2-yl)cyclohexa-1,3-dienecarbaldehyde; 6-methyl-4,6-diphenylcyclohexa-1,3-dienecarbaldehyde; 6-methyl-4,6-di(naphthalen-2-yl)cyclohexa-1,3-dienecarbaldehyde; 4,6-bis((E)-4,8-dimethylnona-3,7-dienyl)-6-methylcyclohexa-1,3-dienecarbaldehyde; cis-4-methyl-5-(3-methyl-but-2-enyl)-6-phenyl-cyclohexa-1,3-dienecarbaldehyde; trans-4-methyl-5-(3-methyl-but-2-enyl)-6-phenyl-cyclohexa-1,3-dienecarbaldehyde; cis and trans-6-(4-dimethylamino-phenyl)-4-methyl-5-(3-methyl-but-2-enyl)-cyclohexa-1,3-dienecarbaldehyde; 6-(4-(dimethylamino)phenyl)-4-methylcyclohexa-1,3-dienecarbaldehyde; 4-methyl-6-(4-nitrophenyl)cyclohexa-1,3-dienecarbaldehyde; 4-methylcyclohexa-1,3-dienecarbaldehyde; 4-hexyl-6-phenylcyclohexa-1,3-dienecarbaldehyde; 6-(4-(dimethylamino)phenyl)-4-hexylcyclohexa-1,3-dienecarbaldehyde; 4,6-diphenylcyclohexa-1,3-dienecarbaldehyde; 6-(4-(dimethylamino)phenyl)-4-phenylcyclohexa-1,3-dienecarbaldehyde; 6-(4-nitrophenyl)-4-phenylcyclohexa-1,3-dienecarbaldehyde; 4-(naphthalen-2-yl)-6-phenylcyclohexa-1,3-dienecarbaldehyde; 6-(4-(dimethylamino)phenyl)-4-(naphthalen-2-yl)cyclohexa-1,3-dienecarbaldehyde; 4-(naphthalen-2-yl)-6-(4-nitrophenyl)cyclohexa-1,3-dienecarbaldehyde; 4-(naphthalen-2-yl)cyclohexa-1,3-dienecarbaldehyde; (E)-4-(4,8-dimethylnona-3,7-dienyl)cyclohexa-1,3-dienecarbaldehyde; (E)-4-(4,8-dimethylnona-3,7-dienyl)-6-phenylcyclohexa-1,3-dienecarbaldehyde; (E)-6-(4-(dimethylamino)phenyl)-4-(4,8-dimethylnona-3,7-dienyl)cyclohexa-1,3-dienecarbaldehyde; 5-methyl-6-(4-nitrophenyl)-4-(thiophen-2-yl)cyclohexa-1,3-dienecarbaldehyde; 6-(4-(dimethylamino)phenyl)-5-methyl-4-(thiophen-2-yl)cyclohexa-1,3-dienecarbaldehyde; 5-methyl-6-phenyl-4-(thiophen-2-yl)cyclohexa-1,3-dienecarbaldehyde; 5-methyl-4-(thiophen-2-yl)cyclohexa-1,3-dienecarbaldehyde; 5-(4-methyl-pent-3-enyl)-4′-nitro-biphenyl-2-carbaldehyde; 4″-dimethylamino-[1,1′;3′,1″]terphenyl-4′-carbaldehyde; 4′″-dimethylamino-[1,1′;4′,1″;3″,1′″]quaterphenyl-4″-carbaldehyde; 4′-dimethylamino-5-(9H-fluoren-2-yl)-biphenyl-2-carbaldehyde; 4′-(dimethylamino)-5-methylbiphenyl-2-carbaldehyde; 5-(9H-fluoren-2-yl)-biphenyl-2-carbaldehyde; and 5-(4-methyl-pent-3-enyl)-biphenyl-2-carbaldehyde.

34. The cyclohexadienal of claim 28, further defined as 4-(biphenyl-4-yl)-6-methyl-6-(5-methylfuran-2-yl)cyclohexa-1,3-dienecarbaldehyde.

35. The cyclohexadienal of claim 28, further defined as 4,6-dihexyl-6-methylcyclohexa-1,3-dienecarbaldehyde.

36. The cyclohexadienal of claim 28, further defined as 6-(4-(dimethylamino)phenyl)-4-(naphthalen-2-yl)cyclohexa-1,3-dienecarbaldehyde.

37. The cyclohexadienal of claim 28, wherein the cyclohexadienal is substantially pure.

38. A pharmaceutical composition comprising a cyclohexadienal of claim 28.

39. A method of preparing a fluorescent compound, comprising aromatization of a cyclohexadienal of claim 28.

40. The method of claim 39, wherein the aromatization occurs naturally.

41. The method of claim 40, wherein either R5 or R6 of the cyclohexadienal of claim 28 is an aryl group.

42. The method of claim 41, wherein the aryl group is a phenyl group.

43. The method of claim 40, wherein the cyclohexadienal of claim 28 is further defined as 4-(4-methyl-pent-3-enyl)-6-(4-nitro-phenyl)-cyclohexa-1,3-dienecarbaldehyde.

44. The method of claim 39, wherein the aromatization comprises reacting the cyclohexadienal of claim 28 in the presence of potassium permanganate under acidic conditions.

45. The method of claim 44, wherein either R5 or R6 of the cyclohexadienal of claim 28 is an aryl group.

46. The method of claim 45, wherein the aryl group is a phenyl group.

47. The method of claim 44, wherein the cyclohexadienal of claim 28 is further defined as 4-(4-methylpent-3-enyl)-6-phenylcyclohexa-1,3-dienecarbaldehyde.

48. A method of stimulating neurite growth, comprising administering to a cell an effective amount of the cyclohexadienal of claim 28.

49. The method of claim 48, wherein the cyclohexadienal of claim 28 comprises a substituent selected from the group consisting of naphthyl, biphenyl and farnesyl.

50. The method of claim 49, wherein the substituent of the cyclohexadienal of claim 28 is at position R5 or R6.

51. The method of claim 48, wherein the cyclohexadienal is selected from the group consisting of 4-(biphenyl-4-yl)-6-methyl-6-(5-methylfuran-2-yl)cyclohexa-1,3-dienecarbaldehyde, 4,6-dihexyl-6-methylcyclohexa-1,3-dienecarbaldehyde and 6-(4-(dimethylamino)phenyl)-4-(naphthalen-2-yl)cyclohexa-1,3-dienecarbaldehyde.