Fluorazone (9H-pyrrolo[1,2-a]indol-9-one) I and its analogues represent valuable intermediates in the synthesis of biologically active compounds. They have been extensively studied in relation to a variety of activities showed by many of their functionalized derivatives. In particular, we found that some N’-heteroacyl-hydrazone derivatives II possess noticeable cytotoxic activity against a colon cancer cell line [1], while thienopyrrolizinones III (known as tripentones) have been showed to act as microtubule polymerization inhibitors [2]. A number of synthetic strategies have been therefore developed for the preparation of (un)substituted-fluorazones and analogs. Amongst the known synthetic methods, the most appealing appear those deriving from ortho-(1H-pyrrol-1-yl)aryl and heteroaryl carboxylic acids, in turn obtained by pyrrolation of ortho-aminoaryl (anthranilic) and ortho-aminoheteroaryl carboxylic acids, respectively [3]. We herein investigated the possibility of directly converting anthranilic acids into fluorazones, through a sequential one-pot pyrrole formation/cyclization, by using DMTHF and 4-chloropyridine hydrochloride as the acid catalyst (Fig. 1). This allows the preparation of fluorazone based derivatives from ortho-aminoaryl and heteroaryl carboxylic acids in generally good yield and after a simple work-up, avoiding any intermediate manipulation. A further advantage of the present procedure lies in the easy availability of the starting aminoacids, most of which are commercial reagents.
One-pot transformation of anthranilic acids to fluorazone derivatives, valuable intermediates for the synthesis of anticancer agents.
AIELLO, Francesca;Garofalo A;GRANDE, Fedora
2011-01-01
Abstract
Fluorazone (9H-pyrrolo[1,2-a]indol-9-one) I and its analogues represent valuable intermediates in the synthesis of biologically active compounds. They have been extensively studied in relation to a variety of activities showed by many of their functionalized derivatives. In particular, we found that some N’-heteroacyl-hydrazone derivatives II possess noticeable cytotoxic activity against a colon cancer cell line [1], while thienopyrrolizinones III (known as tripentones) have been showed to act as microtubule polymerization inhibitors [2]. A number of synthetic strategies have been therefore developed for the preparation of (un)substituted-fluorazones and analogs. Amongst the known synthetic methods, the most appealing appear those deriving from ortho-(1H-pyrrol-1-yl)aryl and heteroaryl carboxylic acids, in turn obtained by pyrrolation of ortho-aminoaryl (anthranilic) and ortho-aminoheteroaryl carboxylic acids, respectively [3]. We herein investigated the possibility of directly converting anthranilic acids into fluorazones, through a sequential one-pot pyrrole formation/cyclization, by using DMTHF and 4-chloropyridine hydrochloride as the acid catalyst (Fig. 1). This allows the preparation of fluorazone based derivatives from ortho-aminoaryl and heteroaryl carboxylic acids in generally good yield and after a simple work-up, avoiding any intermediate manipulation. A further advantage of the present procedure lies in the easy availability of the starting aminoacids, most of which are commercial reagents.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.