Thesis (Ph.D.)--University of California, Berkeley, 1959. / "Chemistry General" -t.p. "TID 04500 (15th Ed.)" -t.p. Includes bibliographical references (p. 115).

The stilbene structure is part of many biologically active natural products, and these compounds can be attractive targets for chemical synthesis. A convergent synthetic design can be utilized in order to install the central olefinic moiety by way of organophosphorus compounds. This design has been employed to prepare a number of natural products, including the potent anti-cancer compounds known as the schweinfurthins and many analogues thereof. Not only do all these structures consist of a stilbenoid scaffold, but all are partially terpenoid in nature as well. Striking similarities to the schweinfurthins would become apparent following the isolation of a new group of compounds, which would later become known as the pawhuskins. In 2004, Belofsky and co-workers reported a small set of prenylated stilbenes that they named pawhuskins. Pawhuskins A-C were isolated from the common North American purple prairie clover (Dalea purpurea) collected near Pawhuska, Oklahoma. Belofsky's findings support an ethnomedical use, because the pawhuskins were shown to modulate opioid receptors through displacement of a nonselective radioactive antagonist (3[H]-naloxone) striatal tissue taken from rat brain. Pawhuskin A was the most potent member of the family, making it one of a small group of compounds that does not contain a basic nitrogen atom but that still exhibits effects on the opiate receptor system. This activity is surprising given the absence of the traditional pharmacophore, a 6-membered piperidine ring containing a basic nitrogen. In these studies, we will report the opioid receptor binding affinity and selectivity of pawhuskin A using a functional assay based on [35S]GTP-γ-S binding. Because of our well-established history of synthesizing prenylated stilbenes, and the unique biological activity of the pawhuskins, we embarked on a synthetic effort targeted at pawhuskin analogues. The preparation of sixteen analogues will be presented. The structure-activity relationship studies of twenty compounds correlated to illuminate more information on the novel pawhuskin pharmacophore will also be reported. Efforts toward preparation of more water-soluble structures similar to the pawhuskins will also be described. The interrelated studies involving pawhuskin analogue synthesis and elucidation of the novel pharmacophore, as well as interesting chemical findings, will be discussed in detail.

Thesis (Ph. D.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 169-186). Also available in print.

(¤@)FVP of (4-Methoxystyryl)pyridenes gave the corresponding phenol products 18 and tricyclic products 20, which all included indene structure. (¤G)FVP of ortho-Chlorostyrylarenes gave the cyclized prodccts 17, which eliminated chloro group. Photolytic study of ortho-Chlorostyrylarenes gave chloro-containing cyclized products 22.

Flash vacuum pyrolysis (FVP) of 2-azidocycloheptanone gave two products: 3,4,5,6-tetrahydro-1H-azocin-2-one and 1-hydroxy-2-oxo-4- azabicyclo[5.3.0]dec-4-ene-3-spiro-2¡¦-cycloheptanone. Flash vacuum pyrolysis of 2-[2-(4-methoxyphenyl)vinyl]benzofuran gave two products: 4-(2-benzofuran-2-ylvinyl)phenol and 1H-6-oxacyclopenta[c]fluorine.

Abstract¡G ¤@¡B trans o-Thiomethoxystilbene and its derivatives 19a-c had been studied by means of pyrolysis and photolysis. Under pyrolytic conditions, compounds 19a-c gave not only the products 24¡B30¡B33,but also their corresponding isomers 26¡B31¡B34 . Furthermore, compound 19c gave dibenzothiophene (32) as the major product by opening the furan ring at higher temperature. Under photolytic conditions, compounds 19a-c gave the corresponding photocyclic products 40¡B44¡B46. With the exception of 19c, photolysis of 19a and 19b also gave 24 and 30, respectively. ¤G¡B For synthetic study of thieno-fused derivatives 4 and 5 of truxene, preparation monomer 6 and 7 can be accomplished in two steps by means of flash vacuum pyrolysis.

published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

Pyrolysis of 3- (o-methoxyphenyl)-1-phenylprop-2-en-1-one(49) ¡B1- (o-methoxyphenyl)-3-phenylprop-2-en-1-one (50) and 1-(o-methoxyphenyl)-3-phenylprop -2-yn-1-one (51) gave the expected cyclic products 2-phenylbenzo[b]furan (11) and flavone (73). Furthermore, compounds 49-51 gave phenanthrene-9,10-dione (71)¡Bfluoren-9-one (14) and others as the minor products at high temperture. Under photolytic condition, compounds 49-51 gave photocyclic product (73) all in low yields and recovered mostly the starting materials.

¤@.Pyrolysis of 2-thiomethoxystyrylarenes 15a-c gave 2-(aryl-2-yl)benzo[b]arenes 22a-c and their isomers 23a-c and polycyclic aromatic hydrocarbons (PAH) 24a-c, respectively. Furthermore, pyrolysis of 15c also gave compounds 42¡B43¡B44 by breaking C-N single bond of 15c at higher temperature. In addition, photolysis of 15a-c gave photocyclic products 24a-c and 32a-c, respectively. ¤G.Pyrolysis of 2-(3-phenylpropenyl)anisole(18) and 2-(1-phenyl)anisole (19) gave 2-phenylbenzo[b]furan (13)¡Bbenzofuran (27)¡Bethylbenzene (28) and dibenzyl (29) as the main products. ¤T.Attempts to prepare hexaazatriphenylene derivatives 3 were carried by condensation between diamino dihydropyrazine compound 2 and hexaketocyclohexane (1).

¤@¡BFlash vacuum pyrolysis (FVP) of 2-dimethylaminostilbene and its derivatives via elimination of methyl radical followed by cyclization gave quinoline and 1-methylindole and 3-phenylquinoline and 3-phenylindole. On the other hand, Photolysis of 2-dimethylaminostilbene and its derivatives via electrocyclization gave 1-dimethylaminophenanthrene, phenanthrene, 2-(4-methoxy-phenyl)-1-methyl-1H- quinolin-4-one and 1-methyl-1H-indol-2-yl)phenylmethanone. Photolysis of 2,4'-dimethoxystilbene in acidic sulotion gave 1,6-dimethoxypheanthrene and 1-methoxypheanthrene and ketone compound via electrocyclization followed by [1,9] hydrogen shift. ¤G¡BFVP of 2-(2-chlorostyryl)pyridine gave benzo[f]quinolin, benzo[h]quinolin, on the other hand, FVP of 4-(2-chlorostyryl)pyridine gave different benzo[h]quinolin.