| Research Abstract |
Pyrroloiminoquinone marine alkaloids have received considerable attention due to their potential antitumor activity. In this reserch project we have developed new and efficient methods for both construction and functionalization of pyrroloiminoquinone nucleus based mainly upon directed lithiation strategy.
Thus, 1-triisopropylsily-6-methoxygramine was chlorinated at 4-position of the indole ring via directed lithiation followed by a reaction with hexachloroethane. The chlorinated gramine was converted to 1-protected-6-methoxytryptamine derivatives by conventional procedure. The tryptamines were cyclized to the key tricyclic 7-methoxy- 1, 3, 4, 5 -tetrahydropyrrolo[4, 3, 2- de] quinolincs by aryne-mediated cyclization. The Fremy's salt or salcomine-catalyzed oxidation of the tricyclic compounds produced the 7-methoxy-pyrroloiminoquinones, which were converted to the pyrroloiminoquinone marine alkaloids makaluvamines A, D, 1, and K by the reactions with ammmonium chloride or tyramine hydrochloride (Tetrahedron, 1998, 54, 8999).
Next, the 6-selective functionalization of 1, 3, 4, 5-tetrahydropyrrolo[4, 3, 2-de] quinoline nucleus has been developed via N-Boc-directed lithiation. By using this method, the first total synthesis of veiutamine, a new type of pyrroloiminoquinone marine alkaloid bearing a p-hydroxybenzyl substituent at C-6 position has been achieved. This procedure is useful for the synthesis of a number of 6-substituted pyrroloiminoquinone marine alkaloid analogues, which are essential for structure-activity relationshiip studies of this type of potential antitumor compounds (Tetrahedron Letters, 1999, 40, 1713).
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