A divergent approach to the total synthesis of the marine pyridoacridine alkaloid eilatin and its synthetic isomer isoeilatin

Pyridoacridines in the 21st Century

“…A total synthesis of the heptacyclic pyridoacridine alkaloid eilatin and its isomer isoeilatin was performed starting from pyridoacridones 78 or 181 respectively. [109] The pyridoacridone 78 was obtained (Scheme 56) by condensation of acridone 177 with DMFDEA (cf. Scheme 18) followed by ring closure with hydroxylamine hydrochloride to give the N-oxide 178.…”

“…Synthesis of 4H-pyrido [2,3,4-kl]acridin-4-one 78. [109] Oxidative amination of 78 with 2-aminoacetophenone using cerium(III) chloride catalyst followed by cyclization gave the hexacyclic pyridoacridone 180 which was transformed into eilatin by an annulation reaction using another DMFDEA procedure (Scheme 55).…”

New Perspectives in the Chemistry of Marine Pyridoacridine Alkaloids

“…A divergent synthesis leading to both eilatin ( 90 ) and its isomer isoeilatin ( 119 ) was published by Plodek and Bracher in 2015 [ 37 ]. This approach started with a Friedländer reaction of 2-aminoacetophenone ( 7 ) and 1,3-cyclohexanedione ( 110 ) to afford acridone 111 .…”

“…The final annulation of ring G was performed in a one-pot reaction by condensation of the acidic methyl group with N , N -dimethylformamide diethyl acetal, followed by heating with ammonium chloride/glacial acetic acid to give 90 . Hence, alkaloid 90 was synthesized in seven steps with an overall yield of 6.9% from only two building blocks (1,3-cyclohexanedione, 2-aminoacetophenone) ( Scheme 20 ) [ 37 ].…”

“…In analogy to the above-mentioned protocol, N -oxide 117 was subjected to Boekelheide rearrangement, ester hydrolysis and oxidation with MnO 2 to furnish pyridoacridone 118 . The following steps (oxidative amination, acid-catalyzed cyclization, annulation of the seventh ring using N , N -dimethylformamide diethyl acetal and ammonium chloride) were performed in full analogy to the above-mentioned total synthesis of eilatin ( 90 ) [ 37 ]. Isoeilatin ( 119 ) was obtained in eight steps with 5.1% total yield ( Scheme 21 ) [ 37 ].…”