Synthesis of Ascididemine and an Isomer

Abstract

Ascididemine (9H‐quino[4,3,2‐de][1,10]phenanthrolin‐9‐one) (1) and an isomer (9H‐quino[4,3,2‐de][1,7]phenanthrolin‐9‐one) (4) have been synthesized starting from 1,4‐dimethoxyacridone (7). The acridone was converted into 1,4‐dimethoxy‐9‐ethynylacridine (11) by a triflate coupling. The ethynylacridine was converted in one‐pot into 3H‐6‐methoxypyrido[2,3,4‐kl]acridine (15) by reaction with sodium diformylamide; the mechanism of this key transformation is discussed. Conversion into 6H‐4‐bromopyrido[2,3,4‐kl]acridin‐6‐one (19) and 6H‐pyrido[2,3,4‐kl]acridin‐6‐one (17), followed by reaction of each of these under high pressure conditions with acrolein N,N‐dimethylhydrazone, gave ascididemine and its isomer, respectively.

Pyridoacridines in the 21st Century

“…Synthesis of arnoamine A skeleton from an indole. [65,66] The Authors' synthesis of ascididemine began with the acridone 105 (Scheme 32) [67] converted as shown into ethynylacridine 106. The next step was entirely novel involving reaction with sodium diformylamide and producing the "top" pyridine ring directly 107.…”

High-Pressure Cycloaddition Reactions in the Synthesis of Biologically Relevant Heterocycles

“…Álvarez applied aza hetero Diels-Alder reaction [60] in synthesis of ascididemine and its isomer (Scheme 39). Aza hetero Diels-Alder cycloadditions of propenal N,N-dimethylhydrazone with quinone imines 159 and 160 afforded pyridine ring (D-ring of ascididemine) after oxidation step.…”

Syntheses of 7H-pyrido-and 7H-pyrano[2,3,4-kl]acridin-2(3H)-ones from 9-chloroacridines

“…In the case of ethyl malonate, the cyclization yielded a mixture of 2 ethoxy 1 ethoxycarbonyl 7 methyl 7H pyrido [2,3,4 kl]acridine (2b) and 1 ethoxycarbonyl 7 methyl 7H pyrido[2,3,4 kl]acridin 2(3H ) one (3b) in approximately the same ratio as for products 2a and 3a.…”

“…Earlier, 1 we have described the synthesis of pyrido[kl]acridines by cyclization of 1 acylamino acridones. Treatment of aminoacridone 1 with PCl 5 in benzene and then with a CH acid in the presence of a base directly gave pyri do [2,3,4 kl]acridine derivatives. A literature example of [kl]annula tion of a heterocycle with acridine is a transformation of 9 ethynyl 1,4 dimethoxyacridine into 6 methoxy 3H pyrido [2,3,4 kl]acridine in the presence of sodium di formylamide, which is regarded as electrocyclic ring clo sure in the enamide anion.…”

“…Here we present another route to these hetero cycles via replacement of the halogen atom in 1 substi tuted 9 chloroacridine by a C nucleophile followed by an attack of its electrophilic α functional group on the sub stituent in position 1. With ethyl cyanoacetate as a CH acid, 1 cyano 2 ethoxy 7 methyl 7H pyri do [2,3,4 kl]acridine (2a) and 1 cyano 7 methyl 7H pyrido [2,3,4 kl]acridin 2(3H ) one (3a) were obtained in the ratio ~3 : 1 (Scheme 1). 2 9 Chloroacridine containing the amino group in posi tion 1 was generated by a reaction of 1 amino 10 methylacridone (1) with PCl 5 (by analogy with a known 3 reaction of 1 aminoanthraquinone with PCl 5 ).…”