The synthesis of 7-N-formyllavendamycin methyl ester (59), 7-N-formyldemethyl lavendamycin n-octyl ester (60), 7-N-formyldemethyllavendamycin ethyl ester (61), 7-Nformyldemethyllavendamycin amide (62), are described.The Pictet-Spengler condensation of 7-N-formamido-2-formylquinoline-5,8-dione (52) with (3-methyltryptophan methyl ester (4),L-tryptophan ethyl ester (54), DL-tryptophan n-octyl ester (56), DL-tryptophan amide (58) in dry distilled xylene or anisole directly afforded the four lavendamycin analogs 59 - 62.Aldehyde 52 was prepared according to the following general procedure: Nitration of 8-hydroxy-2-methylquinoline (43) with a 70 % mixture of HNO3 / H2SO4 yielded 8-hydroxy2-methyl-5,7-dinitroquinoline (44). Compound 44 was then reduced in the presence of 5 palladium on charcoal in a hydrochloric acid solution to yield 5,7-diamino-8-hydroxy-2 methylquinoline dihydrochloride salt (45). Treatment of the resulting 45 with trimethylacetic formic anhydride (49) at 25° C under an argon atmosphere afforded _5,7-diformamido-8hydroxy-2-methylquinoline (50). Compound 50 was oxidized by potassium dichromate to give the 7-formamido-2-methylqunoline-5,8-dione (51). Oxidation of 51 by selenium dioxide in refluxing dry and distilled 1,4-dioxane afforded 7-formamido-2-formylquinoline5,8-dione (52).Trimethylacetic formic anhydride (49) was prepared according to Fife's method29 by the treatment of sodium formate (47) with trimethylacetic chloride (46) in the presence of poly 4-vinylpyridine-N-oxide (48) as a catalyst in dry acetonitrile at room temperature under argon. Tryptophans 54, 56, and 58 were prepared through the neutralization of L-tryptophan ethyl ester hydrochloride, DL-tryptophan octyl ester hydrochloride and DL-tryptophan amide hydrochloride with a 14 % ammonium hydroxide solution followed by extraction.A sample of P-methyltryptophan methyl ester (4) was given to me by Wen Cai. Ester 4 has been prepared by the method reported by Behforouz et.al.23The structures of the novel compounds 52, 59, 60, 61, 62 were confirmed by iH NMR, IR, EIMS and HRMS.The structures of 44, 45, 49, 50, 51, 54, 56, 58, were also confirmed by 1H NMR and IR spectroscopy. / Department of Chemistry

The synthesis of 6-methoxylavendamycin methyl ester (39) and 6-methoxy detnethyllavendamycin methyl ester (40) is reported. Also the synthesis of 7-propionamido-2-methylquinoline-5,8-dione (33) and 7propionamido-3-methylquinoline-5,8-dione (34) via the Diels-Alder reaction is described.The Pictet-Spengler condensation of 7-amino-6-methoxy-2-formylquinoline-5,8-dione (37) with 8-methyltryptophan methyl ester (4) and tryptophan methyl ester (38), produced respectively the lavendamycin analogs 39 and 40.Aldehyde 37 was prepared by the oxidation of 7-amino-6-methoxy-2methylauinoline-5,8-dione (47) with selenium dioxide under reflux in dry 1,4-dioxane.Our original plan for the synthesis of aldehyde 37 via 7-bromo-6methoxy-2-methylquinoline-5,8-dione (36) was not successful. The DielsAlder reaction of 3-methoxy-2,6-dibromobenzoquinone (35) and N-(O-(t-butyldimethylsilyloxy)]-2-methyl-1-aza-1,3-butadiene (11) gave a very low yield of 36 and consequently this route was abandoned.An alternate known multistep route was chosen to produce the bromoquinolinedione 36. Reaction of 4-methoxy-2-nitroaniline (41) with crotonaldehyde (42) gave 6-methoxy-2-methyl-8-nitroquinoline-5,8-dione (43). Subsequent nitration, reduction, oxidation, and bromination of mononitroquinoline 43 yielded the desired bromoquinolinedione 36 with success. A change to Boger's procedure in the next reaction involving the azido intermediate 46 was done due to its effectiveness in producing a greater yield and purer product than that of Liao's procedure. The final preparation of 7-amino-6-methoxy-2-methylquinoline-5,8-dione (47) was accomplished by the hydrogenation of azidoquinolinedione 46 in the presence of platinum oxide in anhydrous methanol.Two other quinolinediones, 33 and 34, were earlier synthesized using the Diels-Alder reaction. Quinolinediones 33 and 34 were prepared by reacting 2-propionamido-6-bromobenzoquinone (32) with azadienes 11 and 19 to respectively yield 7-propionamido-2-methylquinoline-5,8-dione (33) and 7propionamido-3-methylquinoline-5,8-dione (34).Bromobenzoquinone 32 was prepared according to Kelly's method of preparation. 2,4-Dibromophenol (48) was nitrated, reduced, propionylated, hydrolyzed, and finally oxidized to produce 2-propionamido-6bromobenzoquinone (32). / Department of Chemistry