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
| Identifer | oai:union.ndltd.org:BSU/oai:cardinalscholar.bsu.edu:handle/186555 |
| Date | January 1999 |
| Creators | Erasga, Noe O. |
| Contributors | Behforouz, Mohammad |
| Source Sets | Ball State University |
| Detected Language | English |
| Format | xii, 95 leaves : ill. ; 28 cm. |
| Source | Virtual Press |
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