Isabel Sanchez

A convenient synthesis of pyrrolo[2,1-c][1,4] benzoxazines

Abstract The pyrrolo[2,1- c ][1,4]benzoxazine system was synthesized from 2-fluoroaniline involving an intramolecular nucleophilic displacement of the fluoride atom. The intermediate alcohols 7a and 10 were treated in basic media under strictly controlled conditions which led to the desired tricyclic structure. The unsubstituted alcohol 10 was more stable than the substituted one.

Antitumor agents. Synthesis and biological evaluation of new compounds related to podophyllotoxin, containing the 2,3-dihydro-1,4-benzodioxin system

New compounds with naphtho-fused systems were synthesized and evaluated as antitumor agents. The naphtho-fused systems 6 and 7, synthesized from the hydroxy-acetal, exhibit antitumor activity. The bis(phenylthio) derivatives were considered as possible precursors for lignan lactones (11). The hydroxy-naphthalen 6 showed a significant antineoplastic activity.

Synthesis and Biological Activity of New Class of Dioxygenated Anticancer Agents

This paper describes extensive research on the activity of more of 100 cytotoxic compounds containing an oxygenated ring in their structure and isolated from natural plants or prepared by semisynthesis or synthesis from available intermediates. Anticancer drugs have been classified according to the chemical structure of the natural products that are considered to lead the series. The origin and mechanism of action involved in each case have been considered. This new family of natural, semisynthetic and synthetic products includes compounds with interesting antitumor activity such as podophyllotoxin derivatives, NK-611 (15), TOP-53 (16), NPF (24) and Tafluposide (28); camptothecin analogs such as 45 with a considerable cytotoxicity against beta-cell chronic lymphocytic leukemia (CLL), and 52 (new piperazinyl-CPT analog). New dioxygenated ellipticine analogs showed more activity and stability than the natural pattern when the structure incorporated a lactone function instead of the pyridine ring. In the acridine series the new tetracyclic derivatives 75 and 76 containing ethylenedioxy groups at the 2- and 3-positions of the acridine system exhibited the same activity as m-AMSA in vivo against murine P-388 leukemia. Other isolated compounds containing a dioxygenated ring in their structure such as 100 and 101 showed antitumor activities related to kinase inhibition, and are attractive candidates for development of new synthetic antitumor agents.

Design and synthesis of substituted compounds containing the 1, 4-benzodioxin subunit. New potential calcium antagonists.

New compounds possessing 1,4-benzodioxin or its saturated analogous heterocyclic system were synthesized and tested for calcium antagonist activity. Biological differences were seen between the different modifications applied. These compounds have been shown to be representative of a novel series of calcium channel antagonists.