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
| Identifer | oai:union.ndltd.org:BSU/oai:cardinalscholar.bsu.edu:handle/186686 |
| Date | January 2000 |
| Creators | Sedighi, Minoo |
| Contributors | Behforouz, Mohammad |
| Source Sets | Ball State University |
| Detected Language | English |
| Format | xiii, 111 leaves : ill. ; 28 cm. |
| Source | Virtual Press |
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