¤@.Pyrolysis of 2-(N,N-dimethylamino)styrylarenes (29a-e) and 2-(N,N- benzylmethylamino)styrylarenes (30a-f) both gave 2-(ar-2-yl)- benzo[b]arenes 35a-f, 39a-e, their isomers 36a-e, 40a-e and the other products. On the other hand, photolysis of 29a-e gave electrocyclic products 2, 57b-e and 22a-e, respectively. However photolysis of 30a-f only gave the complicated and unknown compounds. ¤G.Pyrolysis of benzoic 1,3-dimethyl-2-indolyl anhydride (54) gave (1,3-dimethylindol-2-yl)phenylmethanone (63), 1,3-dimethylindole (65) and bis(1,3-dimethylindol-2-yl)methanone (66) as the main products.

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The weak selectivity of chemotherapeutic drugs against tumors has sustained efforts to develop better chemotherapeutic agents that are more potent and selective at destroying tumor cell populations versus normal tissues. This project focuses on evaluating the cell killing effects of the microtubule inhibitor, stilbene 5c, against melanoma cancer. We utilized an in vitro murine melanoma model to study the effects of stilbene 5c on tumor proliferation and survival, as well as growth arrest and cell death. Our findings indicate that stilbene 5c promotes dose dependent cell death in melanomas with the induction of apoptosis and autophagy. The role of autophagy was further assessed using the pharmacological autophagy inhibitor, Bafilomycin A1. It was concluded that autophagy was partially cytoprotective as inhibition of autophagy was shown to induce extensive cell death through an increase in apoptosis. Residual surviving cells were shown to be in a state of growth arrest characterized to be senescence. These findings indicate that stilbene 5c could potentially be developed for the treatment of melanoma.

The secondary structure of peptides is of pivotal importance for their biological function. The introduction of photoswitchable moieties into the backbones of peptides provides a unique way of regulating their conformation using an external stimulus, i.e., light. This thesis addresses the design, synthesis, and conformational analysis of photoswitchable peptidomimetics (PSPM). Examples of photomodulation of their functional properties are given. PSPM were prepared by incorporation of stilbene and thioaurone chromophores (switches) into dipeptides. Synthetic schemes for preparing these chromophores have been developed. Their suitability for incorporation into peptidomimetics has been demonstrated, and the resulting PSPM have been subjected to photoisomerization as well as computational and spectroscopic conformational analysis. The chromophore’s potential as a β-hairpin inducer was particularly interesting. To investigate the factors that govern the formation of β-hairpins, a series of decapeptides were prepared. Turn regions consisting of amino acids or chromophores were combined with antiparallel peptide strands with hydrophobic side chains. Linear tryptophan zipper peptidomimetics and cyclic peptidomimetics with a second, hairpin-inducing turn region were particularly promising. Comparison between switches revealed that the more flexible stilbene is a better choice for upholding the β-hairpin conformation than the thioaurone. The catalytic properties of an artificial hydrolase with a helix-loop-helix structure can be improved by introducing a stilbene photoswitch into the loop region. Photoisomerization regulates the catalytic activity of this peptidomimetic, and provides a means to control its aggregation state. The activity of the enzyme Mycobacterium tuberculosis ribonucleotide reductase was realized by incorporating a stilbene moiety into a linear peptide. Here, one photoisomer proved to be an inhibitor at nM concentrations. A significantly lower effect was observed for the other isomer. Finally, the decomposition of thioaurones, mainly to thioflavonols and thiaindenes, under conditions used for solid-phase peptide synthesis has been mapped. These findings are expected to have implications for future use of this chromophore.

3-(o-(Methylthio)phenyl)-1-phenylprop-2-en-1-one (48) ¡B1-(o-(methylthio)-phenyl)-3-phenylprop-2-en-1-one (49) and 1-(o-(methylthio)phenyl)-3-phenylprop-2-yn-1-one (50) had been studied by means of pyrolysis and photolysis. Under pyrolytic conditions, compound 48 gave phenanthrene (2) as the major product. Both compounds 49 and 50 gave thioflavone (53) as the major product. Under photolytic conditions, compounds 48-50 gave the expected products 2-benzoylbenzo[b]thiophene (51)¡B 2-benzylidenebenzo[b]thiophen-3-one (52) and thioflavone (53), respectively.

1-(o-(Dimethylamino)phenyl)-3-phenylprop-2-en-1-one (62), 3-(o-(dimethylamino)phenyl)-1-phenylpropenone (63) and 1-(o-(dimethyl- amino)phenyl)-3-phenylprop-2-yn-1-one (64) were synthesized and their pyrolytic and photolytic chemistry were studied. Flash vacuum pyrolysis (FVP) of 62 and 64 gave 11H-benzo[a]carbazole (72) and benzo[c]carba-zole (73), FVP of 63 gave phenanthrene (2) and 1-methylquinolin-2(1H)-one (84). Under photolytic conditions, 62 and 64 gave the expected photocyclic products 1-methyl-2-phenylquinolin-4-one (65), while 63 gave the expected photocyclic products (1-methyl-1H-indol-2-yl)phenyl-methanone (66).

Flash vacuum pyrolysis of 2-(2-vinylstyryl)furan derivatives via electrocyclization followed by dehydrogenation will give 2-(2-naphthalen-2-yl)furan analogues, on the other hand, FVP of 2-(2-vinylstyryl)furan derivatives via electrocyclization followed by [1,5]-H shift will give 3-(2-furyl)-1,2-dihydronaphthalene analogues. FVP of 2-[2-(4-methoxyphenyl)vinyl]benzo[b]thiophene gave three products: trans-4-(2-benzo[b]thiophen-2-ylvinyl)phenol, benzo[b]naphtha[1,2-d]thiophen-2-ol and 1H-6-thiacyclopenta[c]fluorene.

1. 2-[2-(2vinylphenyl)ethenyl]thiophene ( 30 ) and 2,2-(o-phenylenedivinylene)dithiophene ( 31 ) were studied under pyrolytic and photolytic conditions, photolytic of 30 gave upon bicyclic product 35, whereas photolytic of 31 gave products 37 and 39, FVP of 30 and 31 gave 34 and 37, respectively,which all include naphthalene nucleus. 2. 2-methoxystilbene ( 17 ) and 3-methoxystilbene ( 18 ) were studied under pyrolytic conditions, FVP of 17 gave single product 2-Phenylbenzo[b]furan ( 23 ), FVP of 18 gave 2-phenanthrol ( 27 ), ( 4-phenanthrol ) ( 28 ), trans-3- hydroxystilbene ( 29 ), Fluoren 9 -one ( 30 ) and a pair of isomer 1H-benz[e]indene ( 11a ) and 3H-benz[e]indene (11b).

The first chapter describe the pyrolytic and photolytic studies of substituted styrylarenes. Flash vacuum pyrolysis (FVP) of (2-(4-methoxystyryl)-N-methylindole) (18) gave (4-vinylphenol) (81)¡B (7-methyl-7H-benzo[c]carbazole) (82)¡B (benzo[c]carbazole) (83)¡B (1,6-dihydrocyclopenta[c]carbazole) (84) and (3,6-dihydrocyclopenta- [c]carbazole) (84'). FVP of 2',3,5-trimethoxystilbene (31) gave 2-(3,5-dihydroxyphenyl)benzo[b]furan) (26) and 2-(3,5-dimethoxy- phenyl)benzo[b]furan (95). FVP of 2-methoxy-4-(methoxymethyl)-1- [2-(4-methoxyphenyl)-1-methylvinyl]benzene (33) gave [2-(4- methoxyphenyl)-3-methylbenzofuran-5-yl]methanol (104)¡B4-(3,5- dimethylbenzofuran-2-yl)phenol (105) and 2-(4-hydroxyphenyl)-3- methylbenzofuran-5-carbaldehyde (106). FVP of 2-(2-chlorostyryl)- benzo[b]furan (44) ¡B2-(2-chlorostyryl)benzo[b]thiophene (45) and 2-(2-chlorostyryl)-N-methylindole (46) gave benzo[b]naphtha[1,2-d]- furan (116)¡Bbenzo[b]naphtho[1,2-d]thiophene (117)¡B7-methyl-7H- benzo[c] carbazole (82) and benzo[c]carbazole (83). FVP of 2-chloro-N-(N-methylindol-2-ylmethylene)aniline (71) gave N-methylindole-2-carbonitrile (124)¡B 7H-indolo[2,3-c]quinoline (125) and indolo[1,2-a]quinoxaline (126). FVP of 2-methoxy -N-(N-methyl- indol-2-ylmethylene)aniline (72) gave N-methylindole-2-carbonitrile (124) ¡B 2-(N-methylindol- 2-yl)benzoxazole (132) and 2-hydroxy- benzonitrile (133). FVP of 2-methylthio-N-(phenylmethylene)aniline (73)¡B2-methylthio-N-(furylmethylene)aniline (74)¡B2-methylthio-N- (benzo[b]thiophen-2-ylmethylene)aniline (75) and 2-methylthio-N- (N-methylindol-2-ylmethylene)aniline (76) gave 2-phenylbenzothiazole (143)¡B2-furylbenzothiazole (144)¡B2-benzo[b]thiophen-2-ylbenzo- thiazole (145)¡B2-(N-methylindol-2-yl)benzothiazole (146)¡B2-(1H- indol-2-yl)benzothiazole (147) and benzothiazole (148).Such a method, via oxygen-carbon bond disconnecting, can synthesize efficiently a nature product, stemofuran A 26. Photolytic study of 2',3,5-trimethoxystilbene (31) gave 1,5,7- trimethoxyphenanthrene) (101). Photolytic studies of 2-(2-chloro- styryl)benzo[b]furan (44) ¡B2-(2-chlorostyryl)benzo[b]thiophene (45) and 2-(2-chlorostyryl)-N-methylindole (46) gave benzo[b]naphtha- [1,2-d]furan (116) and 4-chlorobenzo[b]naphtha[1,2-d]furan (120)¡Bbenzo[b]naphtho[1,2-d]thiophene (117) and 4-chlorobenzo[b]naphtha- [1,2-d]thiophene (120) ¡B7-methyl-7H- benzo[c]carbazole (82) and 4-chloro-7-methyl-7H-benzo[c]carbazole (121). Photolytic studies of 2-methylthio-N-(phenylmethylene)aniline (73)¡B2-methylthio- -N-(furylmethylene)aniline (74)¡B2-methylthio-N-(benzo[b]thiophen-2- ylmethylene)aniline (75) and 2-methylthio-N-(N-methylindol-2- ylmethylene)aniline (76) gave 2-phenylbenzothiazole (143)¡B2-furyl- benzothiazole (144)¡B2-benzo[b]thiophen-2-ylbenzo- thiazole (145)¡B2-(N-methylindol-2-yl)benzothiazole (146)¡B2-(1H-indol-2-yl)benzo- thiazole (147) and 2-(2,4-dimethoxyphenyl)benzothiazole) (60f). Such a method has the potential for preparing drugs and application on material science. (¤G)FVP of 2-inden-1-ylidenemethylthiophene (24) and 2-inden-1-ylidene- methylfuran (25) gave the cyclized products 2-(2'-thienyl)naphthalene (29) and 2-(2'-furyl)naphthalene (32).