This thesis investigates nitrogen derivatives of naphthoquinone.

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Bithiophene and terthiophene derivatives possess interesting antibacterial¡A antifungal¡Aanticancer, and antiviral properties¡CIn order to explore its structure-activity relationships¡Aour laboratory synthesize a series of thiophene derivatives and compounds with en-yne group¡CSynthesis and preliminary anticancer activities will be discussed and described in the thesis¡C

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published_or_final_version / Chemistry / Master / Master of Philosophy

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The synthesis of substituted non-symmetric tropones has proven to be a considerable synthetic challenge. Particularly, a 3,4,6-tnsubstituted tropone which is required for the total synthesis of CP-225,917 is currently being undertaken by our group. / Two approaches towards the synthesis of substituted tropones are presented. Both utilize linear diene precursors which are closed to 7-membered cycloheptene rings via ring closing metathesis. In the first method, linear precursors are synthesized by addition of nucleophilic substituents to carbonyl groups to form alcohol groups. After forming the cycloheptene ring, the alcohol groups are eliminated to form the tropone. The second method uses an oxidation protocol to form a,(3-unsaturation on either side of a cycloheptenone precursor. An attempt towards the synthesis of the desired tropone required for the CP-225,917 synthesis is also presented. / The methods described here use simple inexpensive starting materials and provide access to tropone substitution not readily available through other means.

The synthesis of several 7-substituted analogs of 2-methylquinoline-5,8-dione and their chemistry are described. In this investigation the following compounds were prepared.5,7-Diformamido-8-hydroxy-2-methylquinoline (207), 7-formamido-2methylquinoline-5,8-dione (199), 7-acetamido-2-methylquinoline-5,8-dione (6), 7-isobutyramido-2-methylquinoline-5,8-dione (200), 7-amino-2-methylquinoline-5,8-dione (210), 7-amino-6-chloro-2-methylquinoline-5,8-dione (213), 7-methoxy-2-methylquinoline5,8-dione (214), 7-ethoxy-2-methylquinoline-5,8-dione (215), 7-isopropyloxy-2methylquinoline-5,8-dione (216), 7-amino-5-ethyl-5-hydroxy-2-methylquinoline-8-one (218), 7-acetamido-5-ethyl-5-hydroxy-2-methylquinoline-8-one (220), and 7-chloro-2methylquinoline-5,8-dione (222).Trimetylacetic formic anhydride (206) was prepared according to McGarvy,s 68 method from treatment of sodium formate (204) and trimethylacetyl chloride (203) in the presence of poly (4-vinylpyridine-N-oxide) (205) as catalyst. 7-Formamido-2methylquinoline-5,8-dione (199) was prepared according to the following general procedure. 8-Hydroxy-2-mehylquinoline (5) was reacted with a 70% mixture of HNO3/H2SO4 to produce 5,7-dinitro-8-hydroxy-2-methylquinoline (18). Compound 18 was reduced by H2/Pd-C in the presence of HCl and then the resulting 5,7-diamino-8-hydroxy-2 methylquinolin-5,8-dione hydrochloride salt (198) reacted with trimethylacetic formic anhydride to produce 5,7-diformamido-8-hydroxy-2-methylquinoline-5,8-dione (207). Compound 207 was treated with a solution of potassium dichromate in acetic acid-water mixture to give product 199.7-Acetamido-2-methylquinoline-5,8-dione (6) was prepared from reaction of a solution of 198 with acetic anhydride in the presence of sodium acetate and sodium sulfite followed by oxidation with potassium dichromate in acetic acid-water solution. 7-Isobutyramido-2methylquinoline-5,8-dione (200) was prepared according to following procedure. Treatment of a solution of 198 with isobutyric anhydride in the presence of sodium acetate and sodium sulfite afforded 5,7-diisobutyramido-8-isobutyroxy-2-methylquinoline (212). Partial hydrolysis of 212 in boiling methanol-water mixture gave 5,7-diisobutyramido-8-hydroxy-2methylquinoline (211). Oxidation of 211 by a solution of potassium dichromate in acetic acid-water mixture afforded product 200.7-amino-2-methylquinoline-5,8-dione (210) was prepared from alcoholysis of 7-acylamino-2-methylquinoline-5,8-diones 6, 199,and 200 with methanol and sulfuric acid. 7-Alkoxy-2-methylquinoline-5,8-diones 214, 215, and 216 were prepared from reaction of 7-acetamido compound 6 with alcohols in the presence of sulfuric acid. Reaction of 7-acylamino compounds 6, 199, and 200 with methanol in the presence of hydrogen chloride gas at 60°C afforded 7-amino-6-chloro-2-methylquinoline-5,8-dione (213).Reaction of compound 210 with diethylaluminum cyanide gave 7-amino-5-ethyl-5hydroxy-2-methylquinoline-8-one (218). The same reaction was carried out on compound 6 to give 7-acetamido-5-ethyl-5-hydroxy-2-methylquinoline-8-one (220).1-[(tert-Butyldimethylsilyl)oxy]-2-methyl-l-aza-1,3-butadiene (4) was prepared from treatment of methyl vinyl ketone (210) and t-butylmethylsilylhydroxylamine (202) in dichloromethane in the presence of molecular sieves. Cycloaddition reaction of a solution of 4 in dichloromethane with 2,6-dichloro-1,4-benzoquinone (221) in sealed tube afforded 7-chloro-2-methylquinoline-5,8-dione (222). / Department of Chemistry

The synthesis of 7-N -furoyllavendamycin methyl ester (35), 7-N -furoyl demethyllavendamycin methyl ester (36), 7-N -furoyldemethyllavendamycin ethyl ester (37), 7-N -furoyldemethyllavendamycin propyl ester (38), 7-N -furoyl demethyl lavendamycin butyl ester (39), 7-N -furoyldemethyllavendamycin isoamyl ester (40),7-N -furoyldemethyllavendamycin cyclohexyl ester (41), 7-N -furoyldemethyl lavendamycin octyl ester (42), 7-N -furoyldecarboxydemethyllavendamycin (43), and demethyl lavendamycin isoamyl ester (44) are described. Pictet-Spengler condensation of 7-furoylamino-2-formylquinoline-5, 8-dione (55) with (3-methyltryptophan methyl ester (4), Ltryptophan methyl ester (56), L-tryptophan ethyl ester (57), L-tryptophan propyl ester (58), L-tryptophan butyl ester (59), L-tryptophan isoamyl ester (60), L-tryptophan cyclohexyl ester (61), L-tryptophan octyl ester (62), L-tryptamine (63), in xylene, or anisole afforded ten lavendamycin analogs.Aldehyde 55 was prepared according to the following general procedure.Nitration of 8-hydroxy-2-methylquinoline (30) gave 8-hydroxy-2-methyl-5,7dinitroquinoline (31). Compound 31 was then hydrogenated and acylated with 2-furoyl chloride (or acetic anhydride ) to yield 5,7-difuroylamino-8-hydroxy-2-methylquinoline (53) or 5,7-diacetamino-8-acetoxy-2-methyl- quinoline (33). Compounds 53 and 33 were oxidized by potassium dichromate to give the corresponding 5,8-diones 54, and 27. Treatment of 53, and 27 with selenium dioxide in refluxing wet dioxane afforded compounds 55 and 28.Compound 4 was previously prepared by other members of our group, compounds 56, 57, 59, and 62 were obtained through the neutralization of the corresponding Ltryptophan ester hydrochlorides with a 14% ammonium hydroxide solution followed by extraction. Compounds 58, 60, 61 were synthesized via a Fischer esterification of Ltryptophan with : propyl alcohol, isoamyl alcohol, and cyclohexyl alcohol saturated with hydrogen chloride.The structures of compounds 53, 54, 55, 35, 36, 37, 38, 39, 40, 41, 42, 43, and 44 were confirmed through 1H NMR, IR, EIMS, and HRMS. Elemental analyses of 53, 54, and 55 are also included.The structures of esters 56, 57, 58, 59, 60, 61, 62, and 63 were confirmed by 1H NMR. / Department of Chemistry

published_or_final_version / abstract / Mechanical Engineering / Doctoral / Doctor of Philosophy