Regioselective Alkylation of an Oxonaphthalene-Annelated Pyrrol System

Abstract

Abstract:The regioselective alkylation of an oxonaphthalene-annelated pyrrole system is reported. The regioselectivity of alkylation can be controlled by the selection of the solvent.

2-[4-[Bis(2-chloroethyl)amino]benzyl]-5,5-dimethyl-2,5-dihydro-4H-benzo[e]isoindol-4-one (Cytotoxic Oxonaphthalene-Pyrroles, Part I)

“…As previously published the N-alkylation of 1 [9,10] with BOC-protected 4-aminobenzyl bromide with NaH in DMF afforded selectively 2 [8], following deprotection with trifluoroacetic acid [11] furnished the amine which was treated with ethylene oxide [4]. The resulting diol was converted via its mesylate and subsequent reaction with LiCl [12] to target compound 3.…”

“…(a) To a solution of 2 [8] (1.07 g, 2.56 mmol) in 11.7 mL of dry CH 2 Cl 2 were added dropwise under argon 2.3 mL (30.25 mmol) of triflouroacetic acid. After stirring for 2 h at room temperature the reaction mixture was concentrated under vacuum and the residue was dissolved in ethyl acetate.…”

“…The cytotoxic effects are based on the highly active aziridinium cation intermediates arising from the bis(2-chloroethyl)amine moiety [1]. In continuation of our department's previous studies in the field of antitumor agents [2][3][4][5][6][7][8] we are reporting in this paper the synthesis of the oxonaphthalene annelated pyrrole 3 with an attached side chain containing a bis(2-chloroethyl)amine group. The cytotoxic activity of 3 was evaluated.…”

2-[3-(Aziridin-1-yl)-2-hydroxypropyl]-5,5-dimethyl-2,5-dihydro-4H-benzo[e]isoindol-4-one (Cytotoxic Oxonaphthalene-Pyrroles, Part III)

“…Besides that there are anticancer agents with the aziridine moiety, such as TEPA, thio-TEPA and triethylenemelamine with a 1,3,5-triazine nucleus. In continuation of our department's previous studies in the field of antitumor agents [2][3][4][5][6][7][8][9][10], we are reporting in this paper the synthesis of the oxonaphthalene-annelated pyrrole 2 with an attached side chain containing an aziridine group. The rationale is that the three-membered aziridine ring is struturally analogous to the immoniumintermediate formed from the nitrogen mustards.…”

2-[2-(Aziridin-1-yl)ethyl]-5,5-dimethyl-2,5-dihydro-4H-benzo [e]isoindol-4-one (Cytotoxic Oxonaphthalene-Pyrroles, Part IV)

“…Both compounds are believed to exert their antitumor effects by cross-linking DNA via aziridinium cation intermediates arising from the bis(2-chloroethyl)amine moiety [1]. In continuation of our department's previous studies in the field of antitumor agents [2][3][4][5][6][7][8][9][10], we are reporting in this paper the synthesis of the oxonaphthalene-annelated pyrrole 2 with an attached side chain containing an aziridine group. The rationale is that the three-membered aziridine ring is structurally analogous to the ammonium-intermediate formed from the nitrogen mustards.…”