TANDEM ARYNE CAPTURE-REARRANGEMENT REACTION FOR THE SYNTHESIS OF FLUORESCENT PSEUDOINDOXYL ANALOGUES

The pseudoindoxyl motif are present in a diverse range of biologically active compounds. It is also present in different fluorescent molecules as well making it a very prized scaffold. Despite its impressive properties there is a paucity in the literature for direct synthesis of these motifs. This is especially true for the 2,2-disubstituted 3-oxindoles.

This report discloses a method to preparethesefluorescent 2,2-disubstituted 3-oxindoles, by the means of tandem aryne capture/ cyclisation/ [2,3]-sigmatropic rearrangement cascadein varying yields. The compounds are analogous to proven imaging agents used in whole organisms. Furthermore, the method also represents an efficient way to generate tetrasubstituted carbon-centres, alongside potentially novel biological probes with readily manipulated functional groups.

The effect of substituents on the regiochemical outcome of the nucleophilic addition of substituted benzyne was studied. Reactions with 3-methoxy benzyne, 3-methyl benzyne and 1,2 naphthyne gave a regioslective product as a result of nucleophilic attack on C1. Reactions with 4-mehyl benzyne and 4-methoxy benzyne gave regioisomeric mixture. The [2,3] sigmatropic rearrangements of the N-allyl and N-propargyl ylides were studied. The results show that the propargyl substituents follows a stepwise mechanism unlike the allyl substituent (which follows a concerted process) making it more favourable for [2,3] rearrangements.

The Stokes shift of the synthesised pseudoindoxyls were calculated which showed that the presence of electron donating/ electron withdrawing groups in the para-position of the arene has distinct effect on the photophysical properties of the compound.

Finally, the rearrangement products were also subjected to different biological tests. The products did not show activity against Staphylococcus aureus and Escherichia coli. Some of the compounds did however show potency against human colon cancer cell line.