Biomimetic synthesis of acridone alkaloids

Abstract

of Aberdeen. Scotland AB9 2UECyclisations of 2'-amino-, 2'-acetylamino-. or 2'-methylamino-2-methoxybenzophsnones occur in thz presence of sodium hydride in dimethyl sulphoxide to give acridone alkaloids. This cyclisation has relevance to the biosynthesis of these alkaloids. An alternative cyclisation can occur, giving 4-arylquinolines or 4-arylquinolones.THE acridone alkaloids compiise ca. 35 members pro-mild reduction of 2,4,6-trihydroxy-2'-nitrobenzophenone duced only by the Rutaceae family of higher plants. (5) with zinc dust in ethanol to give solely 1,3-dihydroxy-Their mode of biosynthesis was postulated by Sir Robert 9-acridone (4), presumably via the 2-aminobenzo-R~b i n s o n ,~ who suggested that anthranilic acid con-phenone (6), the keto tautomer (7) of which could underdensed with acetic acid to give the tricyclic acridone go a Schiff's base type condensation.* Methylation of system.one or more of the hydroxy-functions in (5) prevented the early observation that 2-aminobenzaldehyde (1) cyclisation concomitant with reduction. Cyclisation condensed easily with phloroglucinol (2) t o give 1,3-of 2-methoxyaminoor 2-methoxyacetamido-benzodihydroxyacridine (3). Compound (3) can be con-phenones can be achieved at room temperature through verted through oxidation into 1,3-dihydroxy-9-acridone the use of sodium hydride in dimethyl sulphoxide (4) (Scheme 1).whereby 2'-acetamido-2-methoxybenzophenone and related compounds yield g-acridone~.~ Application of this This postulate may have been prompted byIn modern terms this sequence could involve the I reaction of an activated anthranilic acid (as its co-type of cyclisation has now enabled the synthesis of a enzyme) with a triketide to produce an aminobenzo-number of acridone alkaloids. phenone which on cyclisation produces a dihydroxy-Thamnosma montana lo, If. contains both acridone (8 ;9-acridone. In support of this hypothesis, both an-R1 = R2 = R3 = H) and its 10-methyl derivative (8;thranilic and N-methylanthranilic acid have been shown R1 = R2 = H, R3 = Me); the synthesis of acridone experimentally t o be precursors of the acridone alkaloids from 2'-amino-2-niethoxybenzophenone proceeds in 47% in Acronychia baueri and in Glycosmis arborea,' and the yield.g FOI N-methyl-9-acridone (8; R1 = R2 = H, cyclisation step has been achieved quantitatively by Stirling, December 17th, 1974. R.A. Watt, Chem. and Ind., 1,975, 744.

Toluene derivatives as simple coupling precursors for cascade palladium-catalyzed oxidative C–H bond acylation of acetanilides

“…(Table 2, product 3ab) [4] NH O Table 2, product 3ad) [5] NH O Me O Hexane: EtOAc = 1:5, R f = 0. (Table 2, product 3ae) [4] NH O (Table 2, product 3af) [6] NH O…”

Structure–activity relationship studies of acridones as potential antipsoriatic agents. 1. Synthesis and antiproliferative activity of simple N-unsubstituted 10H-acridin-9-ones against human keratinocyte growth

“…Scheme 1 presents the synthesis of monohydroxy-and 1,3-dihydroxy-substituted acridones 5a, 5i, 5t, 5x, 5aae5ee which was accomplished by the classical condensation of a substituted anthranilate with resorcinol or phloroglucinol [26], respectively, in 1-heptanol in the presence of 4-toluenesulfonic acid [27,28]. Methoxy-substituted acridones 5ee5h, 5j, 5m, 5p, 5r, 5w, 5z (Scheme 2), 5gg, 5ii, 5oo, 5ss (Scheme 3) were obtained by the conventional approach [29].…”

Aza-Annulation Strategies in Alkaloid Total Synthesis

“…Elimination of water then furnishes the quinone methide 50, which tautomerizes to 51 and 52. Oxidation then furnishes 1,3dihydroxy-9-acridone (53), 55 in a process related to the Friedländer quinolone synthesis. 56…”