Cyanoacetylation of indoles, pyrroles and amines, and synthetic uses of these products

This thesis is based on an organic synthetic project aimed towards development of small molecules acting on the P2 receptor as well as development of synthetic methods to such molecules (primarily indoles and featuring isatogens in particular). The new methodology includes cyanoacetylation of indoles, pyrroles, amines, and enamines using cyanoacetic acid in acetic anhydride. The molecules obtained (e.g. 3-cyanoacetylindole) could be further functionalized by nitrosation followed by reduction.

Cyanoacetylated anilines carrying an appropriate substituent (e.g NO2) could be cyclized to quinoxaline-N-oxides, a class of molecules which have been considered as analogues to isatogens. The molecule 2,2'-pyridylisatogen tosylate (PIT) is particularly interesting within this class because of its documented interaction with the P2 receptor.

List of scientific papers

I. Slatt J, Bergman J (2002). Oxygenation of 2,3-dihydroindoles. Tetrahedron. 58: 9187-91.
https://doi.org/10.1016/S0040-4020(02)01198-5

II. Slatt J, Romero I, Bergman J (2004). Cyanoacetylation of indoles, pyrroles and aromatic amines with the combination cyanoacetic acid and acetic anhydride. Synthesis. 2670-75.
https://doi.org/10.1055/s-2004-831164

III. Slatt J, Bergman J (2005). Reinvestigation of a synthesis of quinoxaline-N-oxides. [Manuscript]

IV. Slatt J, Janosik T, Wahlstrom N, Bergman J (2004). Synthetic applications of 3-(cyanoacetyl)indoles and related compounds. J Heterocyclic Chem. [Accepted]
https://pubmed.ncbi.nlm.nih.gov/17585820

V. Slatt J, Beslic S, Stensland B, Bergman J (2005). Functionalizations of 3-(cyanoacetyl)indole and 2-(cyanoacetyl)pyrrole. [Manuscript]